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Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Etoposide and Carboplatin in Extensive Stage Small Cell Lung Cancer (SCLC)

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ClinicalTrials.gov Identifier: NCT02499770
Recruitment Status : Completed
First Posted : July 16, 2015
Results First Posted : July 9, 2020
Last Update Posted : August 21, 2020
Sponsor:
Information provided by (Responsible Party):
G1 Therapeutics, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Small Cell Lung Cancer
Interventions Drug: Carboplatin
Drug: Placebo
Drug: Trilaciclib
Drug: Etoposide
Enrollment 122
Recruitment Details The study was conducted at 71 centers in the United States of America and Europe. The first participant enrolled on 26 June 2015 and the last participant completed on 22 February 2019. For Part 1, participants were enrolled from 26 June 2015 to 30 September 2016 and for Part 2, participants were enrolled from 06 October 2016 to 25 April 2017.
Pre-assignment Details Participants were screened within 14 days prior to first study drug administration. Informed consent and brain scans were obtained up to 28 days prior to first study drug administration. A total of 122 participants were enrolled (24 in Part 1 and 98 in Part 2), of which 96 were assigned to treatment.
Arm/Group Title Part 1: Dose Finding/Expansion Part 2: Trilaciclib/Placebo IV With E/P
Hide Arm/Group Description The 1st cohort in Part 1 received trilaciclib 200 mg/m^2, IV once daily on Days 1 to 3 of each 21-day E/P cycle. The 2nd cohort in the Phase 1b dose-finding portion of Part 1 & the Phase 2a expansion cohort in Part 1 received trilaciclib 240 mg/m^2, IV once daily on Days 1 to 3 of each 21-day E/P cycle. Participants received standard E/P chemotherapy in 21-day cycles. Carboplatin dose was calculated using the Calvert formula with a target AUC = 5 (maximum 750 mg) IV on Day 1. Etoposide 100 mg/m^2 was given IV daily on Days 1, 2, & 3 of each 21-day cycle. Trilaciclib was only given with E/P therapy. If E/P therapy was discontinued, trilaciclib was also to be discontinued. The interval between doses of trilaciclib on successive days was not greater than 28 hours & between the dose of trilaciclib & the first dose of chemotherapy on a given day (etoposide or carboplatin) not greater than 4 hours. Eligible participants were randomized (1:1) to trilaciclib or placebo administered IV once daily on Days 1 to 3 with etoposide and carboplatin on Day 1 and etoposide on Days 2 and 3 of 21-day cycles (E/P). Randomization was stratified by ECOG performance status (0 to 1 versus 2). Participants received trilaciclib 240 mg/m^2 (recommended dose from Part 1) or placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle. Participants received standard E/P chemotherapy in 21-day cycles. The carboplatin dose was calculated using the Calvert formula with a target AUC = 5 (maximum 750 mg) IV on Day 1, and 100 mg/m^2 etoposide was administered IV daily on Days 1, 2, and 3 of each 21-day cycle. The interval between doses of trilaciclib/placebo on successive days was not greater than 28 hours and between the dose of trilaciclib/placebo and the first dose of chemotherapy on a given day (etoposide or carboplatin) was not greater than 4 hours.
Period Title: Overall Study
Started 19 77
Completed 0 0
Not Completed 19 77
Reason Not Completed
Death             17             56
Study completion             1             10
Withdrawal by Subject             0             7
Lost to Follow-up             0             2
Subject declined further treatment             1             0
Withdrawn by PI for compassionate reason             0             1
Randomized but not enrolled             0             1
Arm/Group Title Part 1: Dose Finding/Expansion Part 2: Trilaciclib/Placebo IV With E/P Total
Hide Arm/Group Description The 1st cohort in Part 1 received trilaciclib 200 mg/m^2, IV once daily on Days 1 to 3 of each 21-day E/P cycle. The 2nd cohort in the Phase 1b dose-finding portion of Part 1 & the Phase 2a expansion cohort in Part 1 received trilaciclib 240 mg/m^2, IV once daily on Days 1 to 3 of each 21-day E/P cycle. Participants received standard E/P chemotherapy in 21-day cycles. Carboplatin dose was calculated using the Calvert formula with a target AUC = 5 (maximum 750 mg) IV on Day 1. Etoposide 100 mg/m^2 was given IV daily on Days 1, 2, & 3 of each 21-day cycle. Trilaciclib was only given with E/P therapy. If E/P therapy was discontinued, trilaciclib was also to be discontinued. The interval between doses of trilaciclib on successive days was not greater than 28 hours & between the dose of trilaciclib & the first dose of chemotherapy on a given day (etoposide or carboplatin) not greater than 4 hours. Eligible participants were randomized (1:1) to trilaciclib or placebo administered IV once daily on Days 1 to 3 of E/P therapy. Randomization was stratified by ECOG performance status (0 to 1 versus 2). Participants received trilaciclib 240 mg/m^2 (recommended dose from Part 1) or placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle. Participants received standard E/P chemotherapy in 21-day cycles. The carboplatin dose was calculated using the Calvert formula with a target AUC = 5 (maximum 750 mg) IV on Day 1, and 100 mg/m^2 etoposide was administered IV daily on Days 1, 2, and 3 of each 21-day cycle. The interval between doses of trilaciclib/placebo on successive days was not greater than 28 hours and between the dose of trilaciclib/placebo and the first dose of chemotherapy on a given day (etoposide or carboplatin) was not greater than 4 hours. Total of all reporting groups
Overall Number of Baseline Participants 19 77 96
Hide Baseline Analysis Population Description
All participants randomized
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 77 participants 96 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
7
  36.8%
37
  48.1%
44
  45.8%
>=65 years
12
  63.2%
40
  51.9%
52
  54.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 77 participants 96 participants
Female
8
  42.1%
23
  29.9%
31
  32.3%
Male
11
  57.9%
54
  70.1%
65
  67.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 77 participants 96 participants
Hispanic or Latino
1
   5.3%
2
   2.6%
3
   3.1%
Not Hispanic or Latino
18
  94.7%
75
  97.4%
93
  96.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 77 participants 96 participants
American Indian or Alaska Native
0
   0.0%
1
   1.3%
1
   1.0%
Asian
0
   0.0%
1
   1.3%
1
   1.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
  15.8%
1
   1.3%
4
   4.2%
White
16
  84.2%
73
  94.8%
89
  92.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
   1.3%
1
   1.0%
Country  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 77 participants 96 participants
United States
19
 100.0%
39
  50.6%
58
  60.4%
Non-United States
0
   0.0%
38
  49.4%
38
  39.6%
Body Surface Area   [1] 
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 19 participants 75 participants 94 participants
1.90  (0.263) 1.90  (0.216) NA [2]   (NA)
[1]
Measure Analysis Population Description: BSA was only available for 75 of the 77 participants in Part 2.
[2]
Mean body surface area was not calculated for all participants overall.
1.Primary Outcome
Title Number of Participants With Dose Limiting Toxicities by Cohort in Cycle 1, Part 1
Hide Description

Dose-limiting toxicities (DLTs) were drug-related toxicities defined as follows:

  1. Absolute neutrophil count (ANC) < 0.5 × 10^9/L lasting for ≥ 7 days
  2. ≥ Grade 3 neutropenic infection/febrile neutropenia
  3. Grade 4 thrombocytopenia (TCP) or ≥ Grade 3 TCP with bleeding
  4. Unable to start next cycle of chemotherapy due to lack of recovery to an ANC ≥ 1.5 × 10^9/L and platelet count ≥ 100 × 10^9/L
  5. ≥ Grade 3 nonhematologic toxicity (nausea, vomiting, and diarrhea failing maximal medical management; fatigue lasting for > 72 hours)

Toxicities not clearly related to etoposide/carboplatin therapy were also considered for the purposes of determining DLTs.

Time Frame Days 1-21 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description

Safety analysis set - included all enrolled participants (i.e., signed informed consent) who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib).

Part 1: Cohort 1 Trilaciclib 200 mg/m^2 included 1 participant from Part 2 and 1 participant from Part 1 240 mg/m^2 who received 200 mg/m^2.

Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 12 8
Measure Type: Count of Participants
Unit of Measure: Participants
Number of participants meeting ≥1 DLT criteria 2 1
Grade 4 TCP or ≥Grade 3 TCP with bleeding 1 0
Unable to start next cycle of chemotherapy 1 1
2.Primary Outcome
Title Incidence of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Related AEs, Related SAEs, and AEs Leading to Study Drug Discontinuation in Part 1
Hide Description An AE was defined as any untoward medical occurrence in a participant administered a medicinal product that did not necessarily have a causal relationship with this treatment. TEAEs were defined as any AE that started on or after the first dose of study drug and up to the last dose +30 days. SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. Relatedness to study drug was assessed by the investigator. Related refers to those events that were Possibly, Probably, or Definitely Related. AEs with an unknown/not reported onset date were also included.
Time Frame TEAEs were any AE that started on or after the first dose of study drug and up to the last dose +30 days (a minimum of 51 days up to a maximum of 374 days)
Hide Outcome Measure Data
Hide Analysis Population Description

Safety analysis set - included all enrolled participants (i.e., signed informed consent) who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib).

Part 1: Cohort 1 Trilaciclib 200 mg/m^2 included 1 participant from Part 2 and 1 participant from Part 1 240 mg/m^2 who received 200 mg/m^2.

Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 12 8
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE
12
 100.0%
8
 100.0%
Any SAE
4
  33.3%
1
  12.5%
TEAE related to any study drug
10
  83.3%
8
 100.0%
SAE related to any study drug
0
   0.0%
0
   0.0%
TEAE leading to discontinuation of any study drug
0
   0.0%
0
   0.0%
3.Primary Outcome
Title Duration of Severe (Grade 4) Neutropenia in Part 2
Hide Description Severe (Grade 4) neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period. Within each cycle, the duration (days) of severe neutropenia was defined as the number of days from the date of the first ANC value of <0.5 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10^9/L that met the following criteria: 1) occurred after the ANC value of <0.5 × 10^9/L and 2) no other ANC values <0.5 × 10^9/L occurred between this day and end of cycle. The duration of severe neutropenia only included participants who had at least 1 severe neutropenia event in the cycle, and censoring rules were applied for unresolved severe neutropenia in a cycle. For the treatment period, the overall duration of severe neutropenia was the median value among the durations from all cycles.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) - included all randomized participants who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 16 2
Median (Inter-Quartile Range)
Unit of Measure: Days
8
(7 to 8)
3
(2 to 3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo, Part 2: Trilaciclib 240 mg/m^2
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0097
Comments The p-value was calculated using the stratified log-rank test to account for the baseline ECOG status (0-1 vs 2) as the stratification factor. Significance level was set as two-sided 0.2.
Method Stratified log-rank test
Comments p-value calculated using stratified log-rank test with baseline ECOG status (0-1 vs 2) as stratification factor. Significance level was two-sided 0.2.
4.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Trilaciclib in Cycle 1, Part 1
Hide Description Cmax of trilaciclib in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used. For estimation of Cmax, a concentration that was below the limit of quantification (BLQ) was assigned a value of zero if it occurred in a profile before the first measurable concentration. If a BLQ value occurred after a measurable concentration in a profile, and was followed by a value above the lower limit of quantification, then the BLQ was treated as missing data. If a BLQ value occurred at the end of the collection interval (after the last quantifiable concentration) it was treated as missing data. If two BLQ values occurred in succession after Cmax, the profile was deemed to have terminated at the first BLQ value and any subsequent concentrations were omitted.
Time Frame Days 1 and 3 of Cycle 1 for a 21-day cycle
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analysis set - included all participants with evaluable PK profiles for both treatments and analytes.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 8 1
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 Cycle 1 1240  (738) 1570 [1]   (NA)
Day 3 Cycle 1 1620  (1040) 2260 [1]   (NA)
[1]
Not calculable
5.Secondary Outcome
Title Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) for Trilaciclib in Cycle 1, Part 1
Hide Description AUC0-inf of trilaciclib in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used.
Time Frame Days 1 and 3 of Cycle 1 for a 21-day cycle
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set - included all participants with evaluable PK profiles for both treatments and analytes
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 8 1
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
Day 1 Cycle 1 2560  (792) 2280 [1]   (NA)
Day 3 Cycle 1 3110  (693) 2960 [1]   (NA)
[1]
Not calculable (n=1)
6.Secondary Outcome
Title Time of Maximum Observed Concentration (Tmax) of Trilaciclib in Cycle 1, Part 1
Hide Description Tmax of trilaciclib in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used.
Time Frame Days 1 and 3 of Cycle 1 for a 21-day cycle
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set - included all participants with evaluable PK profiles for both treatments and analytes
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 8 1
Median (Full Range)
Unit of Measure: Hours
Day 1 Cycle 1
0.57
(0.45 to 0.98)
0.50 [1] 
(NA to NA)
Day 3 Cycle 1
0.52
(0.47 to 1.00)
0.45 [1] 
(NA to NA)
[1]
Not calculable (n=1)
7.Secondary Outcome
Title Cmax of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1
Hide Description Cmax of etoposide and free and total carboplatin in plasma were determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used. For estimation of Cmax, a concentration that was BLQ was assigned a value of zero if it occurred in a profile before the first measurable concentration. If a BLQ value occurred after a measurable concentration in a profile, and was followed by a value above the lower limit of quantification, then the BLQ was treated as missing data. If a BLQ value occurred at the end of the collection interval (after the last quantifiable concentration) it was treated as missing data. If two BLQ values occurred in succession after Cmax, the profile was deemed to have terminated at the first BLQ value and any subsequent concentrations were omitted.
Time Frame Days 1 and 3 of Cycle 1 for a 21-day cycle (carboplatin was only dosed on Day 1 so there are no Day 3 Cmax values)
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set - included all participants with evaluable PK profiles for both treatments and analytes
Arm/Group Title Part 1: Dose Finding/Expansion
Hide Arm/Group Description:
The 1st cohort in Part 1 received trilaciclib 200 mg/m^2, IV once daily on Days 1 to 3 of each 21-day E/P cycle. The 2nd cohort in the Phase 1b dose-finding portion of Part 1 & the Phase 2a expansion cohort in Part 1 received trilaciclib 240 mg/m^2, IV once daily on Days 1 to 3 of each 21-day E/P cycle. Participants received standard E/P chemotherapy in 21-day cycles. Carboplatin dose was calculated using the Calvert formula with a target AUC = 5 (maximum 750 mg) IV on Day 1. Etoposide 100 mg/m^2 was given IV daily on Days 1, 2, & 3 of each 21-day cycle. Trilaciclib was only given with E/P therapy. If E/P therapy was discontinued, trilaciclib was also to be discontinued. The interval between doses of trilaciclib on successive days was not greater than 28 hours & between the dose of trilaciclib & the first dose of chemotherapy on a given day (etoposide or carboplatin) not greater than 4 hours
Overall Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: μg/mL
Etoposide Day 1 Cycle 1 21.9  (2.70)
Etoposide Day 3 Cycle 1 20.2  (2.40)
Free Carboplatin Day 1 Cycle 1 20.3  (6.83)
Total Carboplatin Day 1 Cycle 1 18.8  (5.45)
8.Secondary Outcome
Title AUC0-inf of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1
Hide Description AUC0-inf of etoposide and free and total carboplatin in plasma were determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used.
Time Frame Days 1 and 3 of Cycle 1 for a 21-day cycle (carboplatin was only dosed on Day 1 so there are no Day 3 AUC0-inf values)
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set - included all participants with evaluable PK profiles for both treatments and analytes
Arm/Group Title Part 1: Dose Finding/Expansion
Hide Arm/Group Description:
The 1st cohort in Part 1 received trilaciclib 200 mg/m^2, IV once daily on Days 1 to 3 of each 21-day E/P cycle. The 2nd cohort in the Phase 1b dose-finding portion of Part 1 & the Phase 2a expansion cohort in Part 1 received trilaciclib 240 mg/m^2, IV once daily on Days 1 to 3 of each 21-day E/P cycle. Participants received standard E/P chemotherapy in 21-day cycles. Carboplatin dose was calculated using the Calvert formula with a target AUC = 5 (maximum 750 mg) IV on Day 1. Etoposide 100 mg/m^2 was given IV daily on Days 1, 2, & 3 of each 21-day cycle. Trilaciclib was only given with E/P therapy. If E/P therapy was discontinued, trilaciclib was also to be discontinued. The interval between doses of trilaciclib on successive days was not greater than 28 hours & between the dose of trilaciclib & the first dose of chemotherapy on a given day (etoposide or carboplatin) not greater than 4 hours
Overall Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: h*μg/mL
Etoposide Day 1 Cycle 1 Number Analyzed 8 participants
131  (44.7)
Etoposide Day 3 Cycle 1 Number Analyzed 9 participants
146  (48.4)
Free Carboplatin Day 1 Cycle 1 Number Analyzed 7 participants
50.5  (14.4)
Total Carboplatin Day 1 Cycle 1 Number Analyzed 9 participants
137  (37.3)
9.Secondary Outcome
Title Tmax of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1
Hide Description Tmax of etoposide and free and total carboplatin in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used.
Time Frame Days 1 and 3 of Cycle 1 for a 21-day cycle (carboplatin was only dosed on Day 1 so there are no Day 3 Tmax values)
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set - included all participants with evaluable PK profiles for both treatments and analytes
Arm/Group Title Part 1: Dose Finding/Expansion
Hide Arm/Group Description:
The 1st cohort in Part 1 received trilaciclib 200 mg/m^2, IV once daily on Days 1 to 3 of each 21-day E/P cycle. The 2nd cohort in the Phase 1b dose-finding portion of Part 1 & the Phase 2a expansion cohort in Part 1 received trilaciclib 240 mg/m^2, IV once daily on Days 1 to 3 of each 21-day E/P cycle. Participants received standard E/P chemotherapy in 21-day cycles. Carboplatin dose was calculated using the Calvert formula with a target AUC = 5 (maximum 750 mg) IV on Day 1. Etoposide 100 mg/m^2 was given IV daily on Days 1, 2, & 3 of each 21-day cycle. Trilaciclib was only given with E/P therapy. If E/P therapy was discontinued, trilaciclib was also to be discontinued. The interval between doses of trilaciclib on successive days was not greater than 28 hours & between the dose of trilaciclib & the first dose of chemotherapy on a given day (etoposide or carboplatin) not greater than 4 hours
Overall Number of Participants Analyzed 9
Median (Full Range)
Unit of Measure: Hours
Etoposide Day 1 Cycle 1
1.08
(0.90 to 2.67)
Etoposide Day 3 Cycle 1
1.00
(0.85 to 1.52)
Free Carboplatin Day 1 Cycle 1
0.52
(0.47 to 0.67)
Total Carboplatin Day 1 Cycle 1
0.52
(0.47 to 0.67)
10.Secondary Outcome
Title Duration of Severe (Grade 4) Neutropenia in Part 1
Hide Description Severe (Grade 4) neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period. Within each cycle, the duration (days) of severe neutropenia was defined as the number of days from the date of the first ANC value of <0.5 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10^9/L that met the following criteria: 1) occurred after the ANC value of <0.5 × 10^9/L and 2) no other ANC values <0.5 × 10^9/L occurred between this day and end of cycle. The duration of severe neutropenia only included participants who had at least 1 severe neutropenia event in the cycle, and censoring rules were applied for unresolved severe neutropenia in a cycle. For the treatment period, the overall duration of severe neutropenia was the median value among the durations from all cycles.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment. No participants had severe (Grade 4) neutropenia in the 240 mg/m^2 arm.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 4 0
Median (Inter-Quartile Range)
Unit of Measure: Days
6
(6 to 7)
11.Secondary Outcome
Title Occurrence of Severe (Grade 4) Neutropenia in Part 1
Hide Description Severe (Grade 4) neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 9
Measure Type: Count of Participants
Unit of Measure: Participants
4 0
12.Secondary Outcome
Title Occurrence of Febrile Neutropenia in Part 1
Hide Description Each febrile neutropenia event (as defined by Common Terminology Criteria for Adverse Events [CTCAE]) was captured as an AE. The occurrence of febrile neutropenia was defined as at least 1 febrile neutropenia event during the treatment period. For the treatment period, the total number of febrile neutropenia events was the number of febrile neutropenia events with a unique start date.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 9
Measure Type: Count of Participants
Unit of Measure: Participants
0 0
13.Secondary Outcome
Title Duration of Grade 3/4 Neutropenia in Part 1
Hide Description Grade 3/4 neutropenia was defined as at least 1 ANC value <1.0 × 10^9/L during the treatment period. Within each cycle, duration (days) of Grade 3/4 neutropenia was defined as the number of days from the date of the first ANC value of <1.0 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥1.0 × 10^9/L that met the following criteria: 1) occurred after the ANC value of <1.0 × 10^9/L and 2) no other ANC values <1.0 × 10^9/L occurred between this day and end of cycle. The duration of Grade 3/4 neutropenia only included participants who had at least 1 Grade 3/4 neutropenia event in the cycle, and censoring rules were applied for unresolved Grade 3/4 neutropenia in a cycle. For the treatment period, the overall duration of Grade 3/4 neutropenia was the median value among the durations of Grade 3/4 neutropenia from all cycles.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 6 3
Median (Inter-Quartile Range)
Unit of Measure: Days
8
(6 to 10)
8
(5 to 9)
14.Secondary Outcome
Title Occurrence of Grade 3/4 Neutropenia in Part 1
Hide Description Grade 3/4 neutropenia was defined as at least 1 ANC value <1.0 × 10^9/L during the treatment period.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 9
Measure Type: Count of Participants
Unit of Measure: Participants
6 3
15.Secondary Outcome
Title Nadir of Absolute Neutrophil Count in Cycle 1, Part 1
Hide Description Cycle nadir was the lowest value for ANC that occurred between start of cycle and end of cycle and was less than the cycle baseline.
Time Frame From baseline to the end of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 9
Mean (Standard Deviation)
Unit of Measure: x 10^9 cells/L
1.198  (0.7241) 1.653  (0.7381)
16.Secondary Outcome
Title Occurrence of Granulocyte-Colony Stimulating Factor (G-CSF) Administration in Part 1
Hide Description Administration of G-CSF was collected with concomitant medications, which were coded using World Health Organization Drug Dictionary (WHO-DD) Version September 2017. A cycle where G-CSF was administered concurrently was identified by comparing the start and stop dates of each administration of G-CSF to the start of cycle and end of cycle. The occurrence of G-CSF administrations was defined as at least 1 cycle with G-CSF administrations during the treatment period. For the treatment period, the total number of G-CSF administrations was the number of cycles with G-CSF administrations.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 9
Measure Type: Count of Participants
Unit of Measure: Participants
5 3
17.Secondary Outcome
Title Occurrence of Red Blood Cell (RBC) Transfusion in Part 1
Hide Description Within a cycle, a RBC transfusion event was defined as either 1) an actual RBC transfusion, or 2) eligible for RBC transfusion (defined as hemoglobin <8.0 g/dL). The occurrence of RBC transfusions was defined as at least 1 cycle with RBC transfusion during the treatment period. For the treatment period, the total number of RBC transfusions was the number of cycles with RBC transfusions.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 9
Measure Type: Count of Participants
Unit of Measure: Participants
4 1
18.Secondary Outcome
Title Change From Baseline of Hemoglobin at the End of Cycle 6, Part 1
Hide Description Blood samples were collected for local clinical laboratory assessment of hemoglobin levels.
Time Frame Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 5 7
Mean (Standard Deviation)
Unit of Measure: g/L
-9.8  (13.27) -20.1  (15.21)
19.Secondary Outcome
Title Occurrence of Erythropoietin Stimulating Agent (ESA) Administration in Part 1
Hide Description Administration of ESAs was collected with concomitant medications, which were coded using WHO-DD Version September 2017. A cycle where an ESA was administered concurrently was identified by comparing the start and stop dates of each administration of an ESA to the start of cycle and end of cycle. The occurrence of ESA administration was at least 1 cycle with an ESA administration during the treatment period. For the treatment period, the total number of ESA administrations was the number of cycles with ESA administrations.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 9
Measure Type: Count of Participants
Unit of Measure: Participants
2 0
20.Secondary Outcome
Title Occurrence of Platelet Transfusion in Part 1
Hide Description Within a cycle, a platelet transfusion event was defined as either 1) an actual platelet transfusion, or 2) eligible for platelet transfusion (defined as a platelet count ≤10 × 10^9/L). The occurrence of platelet transfusions was defined as at least 1 cycle with platelet transfusion during the treatment period. For the treatment period, the total number of platelet transfusions was the number of cycles with platelet transfusions.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 9
Measure Type: Count of Participants
Unit of Measure: Participants
1 0
21.Secondary Outcome
Title Change From Baseline of Platelet Count at the End of Cycle 6, Part 1
Hide Description Blood samples were collected for local clinical laboratory assessment of platelet count.
Time Frame Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 5 7
Mean (Standard Deviation)
Unit of Measure: x 10^9 cells/L
-72.6  (88.38) -59.4  (108.47)
22.Secondary Outcome
Title Change From Baseline of Lymphocyte Count at the End of Cycle 6, Part 1
Hide Description Blood samples were collected for local clinical laboratory assessment of lymphocyte count.
Time Frame Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 5 7
Mean (Standard Deviation)
Unit of Measure: x 10^9 cells/L
0.188  (0.8431) 0.067  (0.4691)
23.Secondary Outcome
Title Occurrence of Dose Reduction in Part 1
Hide Description Dose reductions were not permitted for trilaciclib, per study protocol. Dose reductions for E/P were derived from changes in the protocol-specified dose on the dosing page and corresponded to the reductions for toxicity specified in the protocol. No more than 2 dose reductions of E/P in total were allowed for any participant. Simultaneous reductions in the doses of E/P were counted as 1 dose reduction. For the treatment period, the total number of dose reductions was the number of cycles where there was at least 1 dose reduction.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description

Safety analysis set - included all enrolled participants (i.e., signed informed consent) who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib).

Part 1: Cohort 1 Trilaciclib 200 mg/m^2 included 1 participant from Part 2 and 1 participant from Part 1 240 mg/m^2 who received 200 mg/m^2.

Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 12 8
Measure Type: Count of Participants
Unit of Measure: Participants
2 3
24.Secondary Outcome
Title Occurrence of Infectious SAEs in Part 1
Hide Description SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. An infectious SAE was a serious event in the Medical Dictionary for Regulatory Activities (MedDRA) system organ class "infections and infestations" and a preferred term of anal abscess, bacteraemia, bronchitis, candida infection, chronic sinusitis, conjunctivitis, infection, influenza, nasopharyngitis, oral candidiasis, oral herpes, pharyngitis streptococcal, pneumonia, pneumonia bacterial, respiratory tract infection, sepsis, skin infection, upper respiratory tract infection, urinary tract infection, urosepsis or viral upper respiratory tract infection.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 9
Measure Type: Count of Participants
Unit of Measure: Participants
2 1
25.Secondary Outcome
Title Occurrence of Pulmonary Infection SAE in Part 1
Hide Description SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. A pulmonary infection SAE was a serious event in the MedDRA system organ class "infections and infestations" and a preferred term of bronchitis, influenza, pneumonia, pneumonia bacterial, respiratory tract infection, upper respiratory tract infection or viral upper respiratory tract infection.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 9
Measure Type: Count of Participants
Unit of Measure: Participants
1 0
26.Secondary Outcome
Title Occurrence of IV Antibiotic Administration in Part 1
Hide Description Intravenous antibiotic administration was collected with concomitant medications, which were coded using WHO-DD Version September 2017. A cycle where IV antibiotic was administered concurrently was identified by comparing the start and stop dates of each administration of IV antibiotic to the start of cycle and end of cycle. The occurrence of IV antibiotic administration was defined as at least 1 cycle with IV antibiotic administration during the treatment period. For the treatment period, the total number of IV antibiotic administrations was the number of cycles with IV antibiotic administrations.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 9
Measure Type: Count of Participants
Unit of Measure: Participants
4 1
27.Secondary Outcome
Title Time to First Major Adverse Hematologic Event (MAHE) in Part 1
Hide Description MAHE was a composite endpoint incorporating the measurement of several clinically meaningful aspects of myelopreservation into a single endpoint. The individual components for MAHE were hospitalization for a hematologic event, febrile neutropenia, death related to treatment, dose delay/reduction due to ANC or platelet counts, prolonged severe neutropenia (duration >5 days), RBC transfusion (actual or eligible) and platelet transfusion (actual or eligible). Time to first occurrence of a MAHE event was defined as the first time to observe an interested event among all the components, starting from the first dose date of study drug administration.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 9
Median (Inter-Quartile Range)
Unit of Measure: Months
2.6 [1] 
(0.8 to NA)
3.0 [1] 
(1.0 to NA)
[1]
Not evaluable
28.Secondary Outcome
Title Best Overall Tumor Response Based on Assessments in Part 1
Hide Description Tumor response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Overall visit response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 was derived programmatically using data from target lesions (TLs), non-target lesions (NTLs), & new lesions. Tumor response data were used to determine each participant's time point response & best overall response (BOR). Complete response (CR) was disappearance of all TLs, any pathological lymph nodes selected as TLs must have reduced in short axis to <10 mm. Partial response (PR) was at least a 30% decrease from baseline in the sum of diameters of TLs, as long as criteria for progressive disease (PD) were not met. PD was a ≥20% increase in the smallest sum of diameters of TLs since treatment started (including baseline) and an absolute increase of ≥5 mm. Stable disease (SD) was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time Frame Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% overall survival (OS) events observed (a maximum of 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Response evaluable analysis set included all participants in the safety analysis set who had at least 1 post-baseline tumor assessment, or clinical progression as noted by the investigator before their first post-baseline tumor scan, or who died due to disease progression before their first post-baseline tumor scan.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 8
Measure Type: Count of Participants
Unit of Measure: Participants
CR 0 1
PR 8 7
SD 0 0
PD 1 0
Not evaluable 0 0
Unconfirmed CR 1 0
Unconfirmed PR 0 0
29.Secondary Outcome
Title Best Overall Tumor Response Based on Blinded Independent Central Review (BICR) Assessments in Part 1
Hide Description Tumor response was assessed by CT or MRI. Overall visit response by RECIST v1.1 was determined by BICR. Tumor response data were used to determine each participant's time point response & BOR. CR was disappearance of all TLs, any pathological lymph nodes selected as TLs must have reduced in short axis to <10 mm. PR was at least a 30% decrease from baseline in the sum of diameters of TLs, as long as criteria for PD were not met. PD was a ≥20% increase in the smallest sum of diameters of TLs since treatment started (including baseline) and an absolute increase of ≥5 mm. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time Frame Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% OS events observed (a maximum of 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Response evaluable analysis set included all participants in the safety analysis set who had at least 1 post-baseline tumor assessment, or clinical progression as noted by the investigator before their first post-baseline tumor scan, or who died due to disease progression before their first post-baseline tumor scan.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 8
Measure Type: Count of Participants
Unit of Measure: Participants
CR 1 0
PR 6 8
SD 2 0
PD 0 0
Not evaluable 0 0
Unconfirmed CR 0 0
Unconfirmed PR 2 0
30.Secondary Outcome
Title Progression Free Survival (PFS) Based on Assessments in Part 1
Hide Description Tumor response was assessed by CT or MRI. PFS was defined as the time (months) from date of first dose date of study drug for participants in Part 1 until date of documented disease progression or death due to any cause, whichever occurred first. More specifically, PFS was determined using all the assessment data up until the last evaluable visit prior to or on the date of i) disease progression as defined by RECIST 1.1 or by clinical criteria as determined by the investigator; or ii) withdrawal of consent; or iii) receiving subsequent anticancer therapy, whichever was earlier. For PFS determined using response data derived programmatically, either clinical progression or progression by RECIST (whichever came first) was considered. Median and inter-quartile range of PFS were calculated using the Kaplan-Meier method.
Time Frame Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% OS events observed (a maximum of 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 9
Median (Inter-Quartile Range)
Unit of Measure: Months
5.3
(1.5 to 6.1)
6.3
(5.9 to 9.1)
31.Secondary Outcome
Title OS in Part 1
Hide Description OS was calculated as the time (months) from date of first dose of study drug for participants in Part 1 to the date of death due to any cause. Participants who did not die during the study were censored at the date last known to be alive. Participants lacking data beyond the day of first dose of study drug had their survival time censored at day of first dose of study drug. OS was not censored if a participant received other anti-tumor treatments after the study drugs. Median and inter-quartile range of OS were calculated using the Kaplan-Meier method.
Time Frame Baseline up until death or a maximum of the time at least 70% OS events observed (a maximum of 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2
Hide Arm/Group Description:
Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 10 9
Median (Inter-Quartile Range)
Unit of Measure: Months
10.6
(4.9 to 25.1)
12.8
(9.5 to 13.5)
32.Secondary Outcome
Title Occurrence of Severe (Grade 4) Neutropenia in Part 2
Hide Description Severe (Grade 4) neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 38
Measure Type: Count of Participants
Unit of Measure: Participants
16 2
33.Secondary Outcome
Title Occurrence of Febrile Neutropenia in Part 2
Hide Description Each febrile neutropenia event (as defined by CTCAE) was captured as an AE. The occurrence of febrile neutropenia was defined as at least 1 febrile neutropenia event during the treatment period. For the treatment period, the total number of febrile neutropenia events was the number of febrile neutropenia events with a unique start date.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 38
Measure Type: Count of Participants
Unit of Measure: Participants
3 1
34.Secondary Outcome
Title Duration of Grade 3/4 Neutropenia in Part 2
Hide Description Grade 3/4 neutropenia was defined as at least 1 ANC value <1.0 × 10^9/L during the treatment period. Within each cycle, duration (days) of Grade 3/4 neutropenia was defined as the number of days from the date of the first ANC value of <1.0 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥1.0 × 10^9/L that met the following criteria: 1) occurred after the ANC value of <1.0 × 10^9/L and 2) no other ANC values <1.0 × 10^9/L occurred between this day and end of cycle. The duration of Grade 3/4 neutropenia only included participants who had at least 1 Grade 3/4 neutropenia event in the cycle, and censoring rules were applied for unresolved Grade 3/4 neutropenia in a cycle. For the treatment period, the overall duration of Grade 3/4 neutropenia was the median value among the durations of Grade 3/4 neutropenia from all cycles.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 30 14
Median (Inter-Quartile Range)
Unit of Measure: Days
8
(7 to 13)
8
(6 to 8)
35.Secondary Outcome
Title Occurrence of Grade 3/4 Neutropenia in Part 2
Hide Description Grade 3/4 neutropenia was defined as at least 1 ANC value <1.0 × 10^9/L during the treatment period.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 38
Measure Type: Count of Participants
Unit of Measure: Participants
30 14
36.Secondary Outcome
Title Nadir of Absolute Neutrophil Count in Cycle 1, Part 2
Hide Description Cycle nadir was the lowest value for ANC that occurred between start of cycle and end of cycle and was less than the cycle baseline.
Time Frame From baseline to the end of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 35
Mean (Standard Deviation)
Unit of Measure: x 10^9 cells/L
0.815  (0.6385) 1.899  (1.1930)
37.Secondary Outcome
Title Occurrence of G-CSF Administration in Part 2
Hide Description Administration of G-CSF was collected with concomitant medications, which were coded using WHO-DD Version September 2017. A cycle where G-CSF was administered concurrently was identified bycomparing the start and stop dates of each administration of G-CSF to the start of cycle and end of cycle. The occurrence of G-CSF administrations was defined as at least 1 cycle with G-CSF administrations during the treatment period. For the treatment period, the total number of G-CSF administrations was the number of cycles with G-CSF administrations.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 38
Measure Type: Count of Participants
Unit of Measure: Participants
24 4
38.Secondary Outcome
Title Occurrence of RBC Transfusion in Part 2
Hide Description Within a cycle, a RBC transfusion event was defined as either 1) an actual RBC transfusion, or 2) eligible for RBC transfusion (defined as hemoglobin <8.0 g/dL). The occurrence of RBC transfusions was defined as at least 1 cycle with RBC transfusion during the treatment period. For the treatment period, the total number of RBC transfusions was the number of cycles with RBC transfusions. If a participant did not have any RBC transfusions, they were assigned a value of 0.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 38
Measure Type: Count of Participants
Unit of Measure: Participants
Overall 9 6
On/after Week 5 9 2
39.Secondary Outcome
Title Change From Baseline of Hemoglobin at the End of Cycle 6, Part 2
Hide Description Blood samples were collected for local clinical laboratory assessment of hemoglobin levels.
Time Frame Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 22 20
Mean (Standard Deviation)
Unit of Measure: g/L
-25.9  (14.63) -20.6  (13.83)
40.Secondary Outcome
Title Occurrence of ESA Administration in Part 2
Hide Description Administration of ESAs was collected with concomitant medications, which were coded using WHO-DD Version September 2017. A cycle where an ESA was administered concurrently was identified by comparing the start and stop dates of each administration of an ESA to the start of cycle and end of cycle. The occurrence of ESA administration was at least 1 cycle with an ESA administration during the treatment period. For the treatment period, the total number of ESA administrations was the number of cycles with ESA administrations.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 38
Measure Type: Count of Participants
Unit of Measure: Participants
2 1
41.Secondary Outcome
Title Occurrence of Platelet Transfusion in Part 2
Hide Description Within a cycle, a platelet transfusion event was defined as either 1) an actual platelet transfusion, or 2) eligible for platelet transfusion (defined as a platelet count ≤10 × 10^9/L). The occurrence of platelet transfusions was defined as at least 1 cycle with platelet transfusion during the treatment period. For the treatment period, the total number of platelet transfusions was the number of cycles with platelet transfusions.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 38
Measure Type: Count of Participants
Unit of Measure: Participants
0 2
42.Secondary Outcome
Title Change From Baseline of Platelet Count at the End of Cycle 6, Part 2
Hide Description Blood samples were collected for local clinical laboratory assessment of platelet count.
Time Frame Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 22 20
Mean (Standard Deviation)
Unit of Measure: x 10^9 cells/L
-32.7  (100.20) -54.4  (95.44)
43.Secondary Outcome
Title Change From Baseline of Lymphocyte Count at the End of Cycle 6, Part 2
Hide Description Blood samples were collected for local clinical laboratory assessment of lymphocyte count.
Time Frame Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 22 20
Mean (Standard Deviation)
Unit of Measure: x 10^9 cells/L
-0.203  (0.4382) 0.104  (0.6320)
44.Secondary Outcome
Title Occurrence of Dose Reduction in Part 2
Hide Description Dose reductions were not permitted for trilaciclib, per study protocol. Dose reductions for E/P were derived from changes in the protocol-specified dose on the dosing page and corresponded to the reductions for toxicity specified in the protocol. No more than 2 dose reductions of E/P in total were allowed for any participant. Simultaneous reductions in the doses of E/P were counted as 1 dose reduction. For the treatment period, the total number of dose reductions was the number of cycles where there was at least 1 dose reduction.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description

Safety analysis set - included all enrolled participants (i.e., signed informed consent) who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib).

Part 1: Cohort 1 Trilaciclib 200 mg/m^2 included 1 participant from Part 2 and 1 participant from Part 1 240 mg/m^2 who received 200 mg/m^2.

Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 38
Measure Type: Count of Participants
Unit of Measure: Participants
13 3
45.Secondary Outcome
Title Occurrence of Infectious SAEs in Part 2
Hide Description SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. An infectious SAE was a serious event in the MedDRA system organ class "infections and infestations" and a preferred term of anal abscess, bacteraemia, bronchitis, candida infection, chronic sinusitis, conjunctivitis, infection, influenza, nasopharyngitis, oral candidiasis, oral herpes, pharyngitis streptococcal, pneumonia, pneumonia bacterial, respiratory tract infection, sepsis, skin infection, upper respiratory tract infection, urinary tract infection, urosepsis or viral upper respiratory tract infection.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 38
Measure Type: Count of Participants
Unit of Measure: Participants
2 4
46.Secondary Outcome
Title Occurrence of Pulmonary Infection SAE in Part 2
Hide Description SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. A pulmonary infection SAE was a serious event in the MedDRA system organ class "infections and infestations" and a preferred term of bronchitis, influenza, pneumonia, pneumonia bacterial, respiratory tract infection, upper respiratory tract infection or viral upper respiratory tract infection.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21- day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 38
Measure Type: Count of Participants
Unit of Measure: Participants
1 4
47.Secondary Outcome
Title Occurrence of IV Antibiotic Administration in Part 2
Hide Description Intravenous antibiotic administration was collected with concomitant medications, which were coded using WHO-DD Version September 2017. A cycle where IV antibiotic was administered concurrently was identified by comparing the start and stop dates of each administration of IV antibiotic to the start of cycle and end of cycle. The occurrence of IV antibiotic administration was defined as at least 1 cycle with IV antibiotic administration during the treatment period. For the treatment period, the total number of IV antibiotic administrations was the number of cycles with IV antibiotic administrations.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21- day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 38
Measure Type: Count of Participants
Unit of Measure: Participants
8 8
48.Secondary Outcome
Title Time to First MAHE in Part 2
Hide Description MAHE was a composite endpoint incorporating the measurement of several clinically meaningful aspects of myelopreservation into a single endpoint. The individual components for MAHE were hospitalization for a hematologic event, febrile neutropenia, death related to treatment, dose delay/reduction due to ANC or platelet counts, prolonged severe neutropenia (duration >5 days), RBC transfusion (actual or eligible) and platelet transfusion (actual or eligible). Time to first occurrence of a MAHE event was defined as the first time to observe an interested event among all the components, starting from the first dose date of study drug administration.
Time Frame From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 38
Median (Inter-Quartile Range)
Unit of Measure: Months
1.0
(0.5 to 2.3)
NA [1] 
(3.3 to NA)
[1]
Not evaluable
49.Secondary Outcome
Title Best Overall Tumor Response Based on Assessments in Part 2
Hide Description Tumor response was assessed by CT or MRI. Overall visit response by RECIST v1.1 was derived programmatically using data from TLs, NTLs, & new lesions. Tumor response data were used to determine each participant's time point response & BOR. CR was disappearance of all TLs, any pathological lymph nodes selected as TLs must have reduced in short axis to <10 mm. PR was at least a 30% decrease from baseline in the sum of diameters of TLs, as long as criteria for PD were not met. PD was a ≥20% increase in the smallest sum of diameters of TLs since treatment started (including baseline) and an absolute increase of ≥5 mm. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time Frame Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% OS events observed (a maximum of 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Response evaluable analysis set included all participants in the safety analysis set who had at least 1 post-baseline tumor assessment, or clinical progression as noted by the investigator before their first post-baseline tumor scan, or who died due to disease progression before their first post-baseline tumor scan.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 36
Measure Type: Count of Participants
Unit of Measure: Participants
CR 1 0
PR 19 24
SD 12 9
PD 4 1
Not evaluable 1 0
Unconfirmed CR 0 0
Unconfirmed PR 6 4
50.Secondary Outcome
Title Best Overall Tumor Response Based on BICR Assessments in Part 2
Hide Description Tumor response was assessed by CT or MRI. Overall visit response by RECIST v1.1 was determined by BICR. Tumor response data were used to determine each participant's time point response & BOR. CR was disappearance of all TLs, any pathological lymph nodes selected as TLs must have reduced in short axis to <10 mm. PR was at least a 30% decrease from baseline in the sum of diameters of TLs, as long as criteria for PD were not met. PD was a ≥20% increase in the smallest sum of diameters of TLs since treatment started (including baseline) and an absolute increase of ≥5 mm. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time Frame Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% OS events observed (a maximum of 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Response evaluable analysis set included all participants in the safety analysis set who had at least 1 post-baseline tumor assessment, or clinical progression as noted by the investigator before their first post-baseline tumor scan, or who died due to disease progression before their first post-baseline tumor scan.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 36
Measure Type: Count of Participants
Unit of Measure: Participants
CR 0 1
PR 23 23
SD 10 7
PD 4 2
Not evaluable 0 1
Unconfirmed CR 0 0
Unconfirmed PR 5 4
51.Secondary Outcome
Title PFS Based on Assessments in Part 2
Hide Description Tumor response was assessed by CT or MRI. PFS was defined as the time (months) from date of first dose date of study drug for participants in Part 1 until date of documented disease progression or death due to any cause, whichever occurred first. More specifically, PFS was determined using all the assessment data up until the last evaluable visit prior to or on the date of i) disease progression as defined by RECIST 1.1 or by clinical criteria as determined by the investigator; or ii) withdrawal of consent; or iii) receiving subsequent anticancer therapy, whichever was earlier. For PFS determined using response data derived programmatically, either clinical progression or progression by RECIST (whichever came first) was considered. Median and inter-quartile range of PFS were calculated using the Kaplan-Meier method.
Time Frame Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% OS events observed (a maximum of 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 38
Median (Inter-Quartile Range)
Unit of Measure: Months
5.0
(3.2 to 6.8)
6.1
(4.2 to 9.5)
52.Secondary Outcome
Title OS in Part 2
Hide Description OS was calculated as the time (months) from date of first dose of study drug for participants in Part 2 to the date of death due to any cause. Participants who did not die during the study were censored at the date last known to be alive. Participants lacking data beyond the day of first dose of study drug had their survival time censored at day of first dose of study drug. OS was not censored if a participant received other anti-tumor treatments after the study drugs. Median and inter-quartile range of OS were calculated using the Kaplan-Meier method.
Time Frame Baseline up until death or a maximum of the time at least 70% OS events observed (a maximum of 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 38
Median (Inter-Quartile Range)
Unit of Measure: Months
10.6
(6.9 to 16.9)
10.9
(7.3 to 20.1)
53.Post-Hoc Outcome
Title Duration of Severe (Grade 4) Neutropenia in Cycle 1 of Part 2
Hide Description In addition to deriving severe (Grade 4) neutropenia using the method described for the primary endpoints, an approach was applied that accounted for participants who did not experience a severe neutropenia event in Cycle 1. For the post-hoc analysis, severe neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period. In Cycle 1, the duration (days) of severe neutropenia was defined as the number of days from the date of the first ANC value of <0.5 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10^9/L that met the following criteria: 1) occurred after the ANC value of <0.5 × 10^9/L and 2) no other ANC values <0.5 × 10^9/L occurred between this day and end of cycle. The duration of severe neutropenia was set to 0 for participants who did not experience severe neutropenia in Cycle 1. Data from unscheduled visits and the actual assessment date (rather than visit date) were included in the derivation.
Time Frame From baseline to the end of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized patients who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the FAS were conducted on the basis of the assigned treatment.
Arm/Group Title Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description:
Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
Overall Number of Participants Analyzed 37 36
Median (Full Range)
Unit of Measure: Days
0
(0 to 13)
0
(0 to 3)
Time Frame All AEs occurring from the first date of administration of trilaciclib or placebo + E/P therapy through and including 30 calendar days after the last administration of trilaciclib or placebo + E/P therapy were recorded (a minimum of 51 days up to a maximum of 374 days).
Adverse Event Reporting Description AEs are reported for the safety analysis set which included all enrolled participants (i.e., signed informed consent) who received at least 1 dose of study drug (etoposide, carboplatin, or trilaciclib). Analyses using the safety analysis set were conducted on the basis of the actual treatment.
 
Arm/Group Title Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2 Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Hide Arm/Group Description Participants received trilaciclib 200 mg/m^2 administered intravenously (IV) once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle. One participant was screened and dosed at trilaciclib 200 mg/m^2 for Part 2 of the study without being randomized. AEs for this participant are summarized under the Part 1 trilaciclib 200 mg/m^2 cohort for the safety analysis set. One participant was enrolled in the Part 1 trilaciclib 240 mg/m^2 cohort, but dosed at trilaciclib 200 mg/m^2. AEs for this participant's are presented in the trilaciclib 200 mg/m^2 cohort for the safety analysis set. Participants received trilaciclib 240 mg/m^2 administered IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle. Participants received placebo IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle. Participants received trilaciclib 240 mg/m^2 IV once daily on Days 1 to 3 of each 21-day E/P chemotherapy cycle.
All-Cause Mortality
Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2 Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/12 (75.00%)      8/8 (100.00%)      28/37 (75.68%)      28/38 (73.68%)    
Hide Serious Adverse Events
Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2 Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/12 (33.33%)      1/8 (12.50%)      9/37 (24.32%)      11/38 (28.95%)    
Blood and lymphatic system disorders         
Febrile neutropenia * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 1/38 (2.63%)  1
Anemia * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 2/37 (5.41%)  3 0/38 (0.00%)  0
Anemia macrocytic * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 0/38 (0.00%)  0
Neutropenia * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 0/38 (0.00%)  0
Cardiac disorders         
Cardiac failure chronic * 1  0/12 (0.00%)  0 1/8 (12.50%)  1 0/37 (0.00%)  0 0/38 (0.00%)  0
Acute myocardial infarction * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 0/38 (0.00%)  0
Atrial fibrillation * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 0/38 (0.00%)  0
Myocardial infarction * 1  1/12 (8.33%)  3 0/8 (0.00%)  0 0/37 (0.00%)  0 0/38 (0.00%)  0
Sinus tachycardia * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 0/38 (0.00%)  0
Gastrointestinal disorders         
Diarrhea hemorrhagic * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 0/37 (0.00%)  0 1/38 (2.63%)  1
Nausea * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 0/37 (0.00%)  0 1/38 (2.63%)  1
Pancreatitis * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 0/37 (0.00%)  0 1/38 (2.63%)  1
Stomatitis * 1  0/12 (0.00%)  0 1/8 (12.50%)  1 0/37 (0.00%)  0 0/38 (0.00%)  0
General disorders         
Pyrexia * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 0/38 (0.00%)  0
Infections and infestations         
Pneumonia * 1  1/12 (8.33%)  1 0/8 (0.00%)  0 1/37 (2.70%)  1 2/38 (5.26%)  3
Influenza * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 0/37 (0.00%)  0 1/38 (2.63%)  1
Oral candidiasis * 1  0/12 (0.00%)  0 1/8 (12.50%)  1 0/37 (0.00%)  0 0/38 (0.00%)  0
Upper respiratory tract infection * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 0/37 (0.00%)  0 1/38 (2.63%)  1
Sepsis * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 0/38 (0.00%)  0
Urosepsis * 1  1/12 (8.33%)  1 0/8 (0.00%)  0 0/37 (0.00%)  0 0/38 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Bone pain * 1  1/12 (8.33%)  1 0/8 (0.00%)  0 0/37 (0.00%)  0 0/38 (0.00%)  0
Nervous system disorders         
Cerebrovascular accident * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 0/37 (0.00%)  0 1/38 (2.63%)  1
Epilepsy * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 1/38 (2.63%)  1
Syncope * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 0/37 (0.00%)  0 1/38 (2.63%)  1
Altered state of consciousness * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 0/38 (0.00%)  0
Psychiatric disorders         
Mental status changes * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 0/38 (0.00%)  0
Renal and urinary disorders         
Renal failure * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 0/37 (0.00%)  0 1/38 (2.63%)  1
Respiratory, thoracic and mediastinal disorders         
Respiratory failure * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 2/38 (5.26%)  2
Hemoptysis * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 0/37 (0.00%)  0 1/38 (2.63%)  1
Pulmonary embolism * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 0/37 (0.00%)  0 1/38 (2.63%)  1
Chronic obstructive pulmonary disease * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 0/38 (0.00%)  0
Dyspnea * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 0/38 (0.00%)  0
Vascular disorders         
Deep vein thrombosis * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 0/38 (0.00%)  0
1
Term from vocabulary, MedDRA 20.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: Cohort 1 Trilaciclib 200 mg/m^2 Part 1: Cohort 2 Trilaciclib 240mg/m^2 Part 2: Placebo Part 2: Trilaciclib 240 mg/m^2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/12 (100.00%)      8/8 (100.00%)      36/37 (97.30%)      37/38 (97.37%)    
Blood and lymphatic system disorders         
Neutropenia * 1  5/12 (41.67%)  30 5/8 (62.50%)  14 23/37 (62.16%)  76 9/38 (23.68%)  17
Thrombocytopenia * 1  3/12 (25.00%)  18 2/8 (25.00%)  8 10/37 (27.03%)  35 10/38 (26.32%)  12
Anemia * 1  5/12 (41.67%)  21 1/8 (12.50%)  3 15/37 (40.54%)  45 10/38 (26.32%)  19
Leukopenia * 1  5/12 (41.67%)  29 0/8 (0.00%)  0 5/37 (13.51%)  13 2/38 (5.26%)  2
Gastrointestinal disorders         
Nausea * 1  5/12 (41.67%)  13 4/8 (50.00%)  8 8/37 (21.62%)  9 13/38 (34.21%)  16
Constipation * 1  4/12 (33.33%)  4 4/8 (50.00%)  5 8/37 (21.62%)  8 9/38 (23.68%)  14
Diarrhea * 1  3/12 (25.00%)  6 2/8 (25.00%)  3 7/37 (18.92%)  10 6/38 (15.79%)  11
Abdominal pain upper * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 1/37 (2.70%)  1 7/38 (18.42%)  13
Vomiting * 1  4/12 (33.33%)  7 4/8 (50.00%)  7 5/37 (13.51%)  5 3/38 (7.89%)  3
Stomatitis * 1  0/12 (0.00%)  0 2/8 (25.00%)  4 1/37 (2.70%)  1 2/38 (5.26%)  2
Gastroesophageal reflux disease * 1  0/12 (0.00%)  0 1/8 (12.50%)  1 2/37 (5.41%)  2 2/38 (5.26%)  2
General disorders         
Fatigue * 1  7/12 (58.33%)  12 4/8 (50.00%)  10 6/37 (16.22%)  6 16/38 (42.11%)  21
Edema peripheral * 1  2/12 (16.67%)  3 2/8 (25.00%)  4 2/37 (5.41%)  2 3/38 (7.89%)  4
Non-cardiac chest pain * 1  0/12 (0.00%)  0 0/8 (0.00%)  0 2/37 (5.41%)  2 3/38 (7.89%)  5
Asthenia * 1  1/12 (8.33%)  1 1/8 (12.50%)  1 2/37 (5.41%)  2 1/38 (2.63%)  1
Pyrexia * 1  3/12 (25.00%)  5 1/8 (12.50%)  1 5/37 (13.51%)  5 1/38 (2.63%)  1
Chills * 1  2/12 (16.67%)  5 0/8 (0.00%)  0 2/37 (5.41%)  2 1/38 (2.63%)  1
Infections and infestations         
Pneumonia * 1  1/12 (8.33%)  1 1/8 (12.50%)  2 2/37 (5.41%)  2 2/38 (5.26%)  4
Urinary tract infection * 1  0/12 (0.00%)  0 1/8 (12.50%)  2 2/37 (5.41%)  6 2/38 (5.26%)  2
Injury, poisoning and procedural complications         
Infusion related reaction * 1  1/12 (8.33%)  2 1/8 (12.50%)  1 0/37 (0.00%)  0 3/38 (7.89%)  4
Investigations         
Neutrophil count decreased * 1  0/12 (0.00%)  0 3/8 (37.50%)  3 9/37 (24.32%)  32 3/38 (7.89%)  9
Blood creatinine increased * 1  1/12 (8.33%)  4 2/8 (25.00%)  3 1/37 (2.70%)  1 2/38 (5.26%)  3
Platelet count decreased * 1  0/12 (0.00%)  0 1/8 (12.50%)  1 4/37 (10.81%)  12 3/38 (7.89%)  11
Weight decreased * 1  1/12 (8.33%)  1 1/8 (12.50%)  1 3/37 (8.11%)  3 2/38 (5.26%)  2
Metabolism and nutrition disorders         
Decreased appetite * 1  0/12 (0.00%)  0 1/8 (12.50%)  1 3/37 (8.11%)  4 7/38 (18.42%)  8
Dehydration * 1  1/12 (8.33%)  1 4/8 (50.00%)  7 1/37 (2.70%)  1 0/38 (0.00%)  0
Hyperkalemia * 1  0/12 (0.00%)  0 1/8 (12.50%)  1 1/37 (2.70%)  1 3/38 (7.89%)  5
Hypomagnesemia * 1  0/12 (0.00%)  0 2/8 (25.00%)  3 1/37 (2.70%)  1 2/38 (5.26%)  3
Hyperglycemia * 1  1/12 (8.33%)  1 0/8 (0.00%)  0 2/37 (5.41%)  3 2/38 (5.26%)  2
Musculoskeletal and connective tissue disorders         
Arthralgia * 1  2/12 (16.67%)  2 4/8 (50.00%)  4 3/37 (8.11%)  5 5/38 (13.16%)  5
Pain in extremity * 1  0/12 (0.00%)  0 3/8 (37.50%)  7 3/37 (8.11%)  5 3/38 (7.89%)  4
Back pain * 1  1/12 (8.33%)  1 1/8 (12.50%)  2 2/37 (5.41%)  2 2/38 (5.26%)  3
Neck pain * 1  1/12 (8.33%)  1 1/8 (12.50%)  1 2/37 (5.41%)  2 1/38 (2.63%)  1
Bone pain * 1  1/12 (8.33%)  1 0/8 (0.00%)  0 4/37 (10.81%)  4 0/38 (0.00%)  0
Nervous system disorders         
Dizziness * 1  2/12 (16.67%)  2 3/8 (37.50%)  5 5/37 (13.51%)  5 4/38 (10.53%)  5
Headache * 1  4/12 (33.33%)  12 0/8 (0.00%)  0 3/37 (8.11%)  4 7/38 (18.42%)  7
Dysgeusia * 1  0/12 (0.00%)  0 2/8 (25.00%)  2 4/37 (10.81%)  4 3/38 (7.89%)  3
Neuropathy peripheral * 1  0/12 (0.00%)  0 2/8 (25.00%)  2 1/37 (2.70%)  1 2/38 (5.26%)  3
Psychiatric disorders         
Anxiety * 1  1/12 (8.33%)  1 0/8 (0.00%)  0 2/37 (5.41%)  2 3/38 (7.89%)  3
Insomnia * 1  2/12 (16.67%)  2 1/8 (12.50%)  1 3/37 (8.11%)  3 1/38 (2.63%)  1
Respiratory, thoracic and mediastinal disorders         
Dyspnea * 1  2/12 (16.67%)  2 3/8 (37.50%)  4 5/37 (13.51%)  5 8/38 (21.05%)  11
Cough * 1  1/12 (8.33%)  1 2/8 (25.00%)  2 4/37 (10.81%)  5 5/38 (13.16%)  8
Oropharyngeal pain * 1  0/12 (0.00%)  0 1/8 (12.50%)  1 1/37 (2.70%)  1 3/38 (7.89%)  3
Skin and subcutaneous tissue disorders         
Alopecia * 1  5/12 (41.67%)  5 3/8 (37.50%)  4 11/37 (29.73%)  14 6/38 (15.79%)  6
Night sweats * 1  1/12 (8.33%)  1 0/8 (0.00%)  0 1/37 (2.70%)  1 3/38 (7.89%)  4
1
Term from vocabulary, MedDRA 20.1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The investigator will submit results communications for review by the sponsor at least 60 days prior to expected submission to the intended publisher or meeting committee. This review period may be shortened upon mutual consent. The sponsor may request modification of any publication, presentation or use by the investigator if such activity may jeopardize a patent application, an existing patent, or other proprietary rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chandra Lovejoy
Organization: G1 Therapeutics
Phone: 001 9192991250
EMail: clovejoy@g1therapeutics.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: G1 Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02499770    
Other Study ID Numbers: G1T28-02
2016-001583-11 ( EudraCT Number )
First Submitted: July 8, 2015
First Posted: July 16, 2015
Results First Submitted: May 22, 2020
Results First Posted: July 9, 2020
Last Update Posted: August 21, 2020