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Study to Compare the Safety and Efficacy of CMB305 With Atezolizumab to Atezolizumab Alone in Participants With Sarcoma (IMDZ-C232/V943A-002)

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ClinicalTrials.gov Identifier: NCT02609984
Recruitment Status : Terminated (This study did not meet the efficacy objective)
First Posted : November 20, 2015
Results First Posted : May 14, 2020
Last Update Posted : July 7, 2020
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Immune Design

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Sarcoma
Myxoid/Round Cell Liposarcoma
Synovial Sarcoma
Metastatic Sarcoma
Recurrent Adult Soft Tissue Sarcoma
Locally Advanced Sarcoma
Liposarcoma
Interventions Biological: CMB305
Biological: atezolizumab
Enrollment 89
Recruitment Details  
Pre-assignment Details  
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by intravenous (IV) infusion every 3 weeks (Q3W) for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered intradermally (ID) on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered intramuscularly (IM) and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of New York Esophageal Squamous Cell Carcinoma 1 (NY ESO-1) protein. Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Period Title: Overall Study
Started 45 44
Treated 45 43
Completed 1 5
Not Completed 44 39
Reason Not Completed
Death             29             26
Participation Discontinued by Sponsor             12             10
Lost to Follow-up             1             2
Withdrawal by Subject             0             1
Disease Progression             2             0
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab Total
Hide Arm/Group Description Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein. Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years. Total of all reporting groups
Overall Number of Baseline Participants 45 44 89
Hide Baseline Analysis Population Description
All randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 45 participants 44 participants 89 participants
46.2  (16.52) 46.7  (14.06) 46.4  (15.27)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 44 participants 89 participants
Female
19
  42.2%
19
  43.2%
38
  42.7%
Male
26
  57.8%
25
  56.8%
51
  57.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 44 participants 89 participants
Hispanic or Latino
7
  15.6%
6
  13.6%
13
  14.6%
Not Hispanic or Latino
37
  82.2%
34
  77.3%
71
  79.8%
Unknown or Not Reported
1
   2.2%
4
   9.1%
5
   5.6%
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 45 participants 44 participants 89 participants
White
35
  77.8%
38
  86.4%
73
  82.0%
Asian
3
   6.7%
1
   2.3%
4
   4.5%
Black or African American
1
   2.2%
3
   6.8%
4
   4.5%
American Indian or Alaska Native
2
   4.4%
0
   0.0%
2
   2.2%
Native Hawaiian or Other
2
   4.4%
0
   0.0%
2
   2.2%
Other
2
   4.4%
0
   0.0%
2
   2.2%
Not Reported
0
   0.0%
2
   4.5%
2
   2.2%
[1]
Measure Description: The race is presented for all participants.
1.Primary Outcome
Title Progression-Free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Hide Description PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 modified to use immune-related response criteria (irRC) confirmation and unidimensional tumor measurements as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in tumor burden compared with nadir (at any single time point) in 2 consecutive observations ≥4 weeks apart. If there was no disease progression or death, participants were censored at the date of their last disease assessment. The PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Time Frame Up to approximately 36.1 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all randomized participants who met eligibility criteria for the study and had data recorded in the electronic Case Report Form (eCRF). Participants were included in the treatment group to which they were randomized.
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Overall Number of Participants Analyzed 45 44
Median (95% Confidence Interval)
Unit of Measure: Months
2.6
(1.4 to 2.9)
1.6
(1.5 to 2.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4900
Comments P-value based on a 2-sided stratified log-rank test stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.8568
Confidence Interval (2-Sided) 95%
0.5507 to 1.3330
Estimation Comments Hazard ratio is from Cox proportional hazards model stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
2.Primary Outcome
Title Overall Survival (OS)
Hide Description OS was determined for all participants and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last follow-up. The OS was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Time Frame Up to approximately 36.1 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all randomized participants who met eligibility criteria for the study and had data recorded in the eCRF. Participants were included in the treatment group to which they were randomized.
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Overall Number of Participants Analyzed 45 44
Median (95% Confidence Interval)
Unit of Measure: Months
18.2
(10.1 to 22.1)
18.0
(15.3 to 26.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4737
Comments P-value based on a 2-sided stratified log-rank test stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.2145
Confidence Interval (2-Sided) 95%
0.7131 to 2.0684
Estimation Comments Hazard ratio is from Cox proportional hazards model stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
3.Secondary Outcome
Title Number of Participants Experiencing a Dose-Limiting Toxicity (DLT)
Hide Description

DLTs will be evaluated during the safety run-in period. Any treatment emergent Grade 3 or higher adverse event (AE) that occurs in the first 42 days after initiation of study treatment, that is deemed possibly, probably or definitely related to the combination of CMB305 and atezolizumab will be considered a DLT with the following exceptions:

  • Alopecia or vomiting (unless not controlled by optimal anti-emetics)
  • Hepatic enzyme elevations associated with the baseline Grade 2 abnormalities
  • Grade 3 laboratory AEs that are asymptomatic and return to baseline or to Grade 1 within 3 days, unless identified specifically as DLT by the investigator or the Data Monitoring Committee (DMC)
  • Grade 3 fatigue
  • Grade 3 systemic reactions (such as fever, headache, influenza like symptoms, myalgia, malaise, or nausea) that return to baseline or Grade 1 within 3 days of study inoculation
Time Frame Up to approximately 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who participated in the safety run-in period and received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab.
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Overall Number of Participants Analyzed 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
1
  16.7%
1
  16.7%
4.Secondary Outcome
Title Number of Participants Who Experienced At Least One Adverse Event (AE)
Hide Description An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented.
Time Frame Up to approximately 36.1 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab.
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Overall Number of Participants Analyzed 45 43
Measure Type: Count of Participants
Unit of Measure: Participants
44
  97.8%
43
 100.0%
5.Secondary Outcome
Title Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Hide Description An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented.
Time Frame Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab.
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Overall Number of Participants Analyzed 45 43
Measure Type: Count of Participants
Unit of Measure: Participants
6
  13.3%
6
  14.0%
6.Secondary Outcome
Title Progression-Free Survival (PFS) Rate at Month 3 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Hide Description PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first, per RECIST 1.1 modified to use irRC confirmation and unidimensional tumor measurements as assessed by BICR. PD was defined as ≥20% increase in tumor burden compared with nadir (at any single time point) in 2 consecutive observations ≥4 weeks apart. If there was no disease progression or death, participants were censored at the date of their last disease assessment. The PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data. Participants were evaluated every 6 weeks with radiographic imaging to assess their response to treatment. The PFS rate was calculated as the percentage of participants with PFS at Month 3.
Time Frame Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all randomized participants who met eligibility criteria for the study and had data recorded in the eCRF. Participants were included in the treatment group to which they were randomized.
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Overall Number of Participants Analyzed 45 44
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
32.6
(19.4 to 46.4)
23.8
(12.4 to 37.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3645
Comments P-value based on a 2-sided stratified log-rank test stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
Method Log Rank
Comments [Not Specified]
7.Secondary Outcome
Title Progression-Free Survival (PFS) Rate at Month 6 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Hide Description PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first, per RECIST 1.1 modified to use irRC confirmation and unidimensional tumor measurements as assessed by BICR. PD was defined as ≥20% increase in tumor burden compared with nadir (at any single time point) in 2 consecutive observations ≥4 weeks apart. If there was no disease progression or death, participants were censored at the date of their last disease assessment. The PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data. Participants were evaluated every 6 weeks with radiographic imaging to assess their response to treatment. The PFS rate was calculated as the percentage of participants with PFS at Month 6.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all randomized participants who met eligibility criteria for the study and had data recorded in the eCRF. Participants were included in the treatment group to which they were randomized.
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Overall Number of Participants Analyzed 45 44
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
16.5
(7.0 to 29.6)
9.5
(3.0 to 20.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3466
Comments P-value based on a 2-sided stratified log-rank test stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
Method Log Rank
Comments [Not Specified]
8.Secondary Outcome
Title Time to Next Treatment (TTNT)
Hide Description TTNT was the time from date of randomization to the start date of subsequent treatment. Participants were treated for up to approximately 2 years and then followed until next treatment or death. Participants who did not receive subsequent treatment were censored at the date of last contact or death. The TTNT was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Time Frame Up to approximately 36.1 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab.
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Overall Number of Participants Analyzed 45 43
Median (95% Confidence Interval)
Unit of Measure: Months
6.2
(4.4 to 9.1)
4.9
(3.3 to 6.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1622
Comments P-value based on a 2-sided stratified log-rank test stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.7006
Confidence Interval (2-Sided) 95%
0.4241 to 1.1574
Estimation Comments Hazard ratio is from Cox proportional hazards model stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
9.Secondary Outcome
Title Distant Metastasis Free Survival (DMFS)
Hide Description DMFS was the time between the date of randomization and the date of first distant metastasis or date of death (whatever the cause), whichever occurs first. Participants without metastasis and death were censored at the date of last contact or death. The DMFS was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Time Frame Up to approximately 36.1 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all randomized participants who met eligibility criteria for the study and had data recorded in the eCRF. Participants were included in the treatment group to which they were randomized.
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Overall Number of Participants Analyzed 45 44
Median (Full Range)
Unit of Measure: Months
5.3
(0.0 to 23.5)
5.5
(0.0 to 31.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6397
Comments P-value based on a 2-sided stratified log-rank test stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.1849
Confidence Interval (2-Sided) 95%
0.5817 to 2.4134
Estimation Comments Hazard ratio is from Cox proportional hazards model stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
10.Secondary Outcome
Title Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) Antibody at Baseline
Hide Description The number of participants with anti-NY-ESO-1 antibodies at baseline was measured using an enzyme-linked immunosorbent assay (ELISA) with recombinant NY-ESO1 protein. A titer of >1:100 was considered positive. The number of participants that were anti-NY-ESO-1 antibody positive at baseline is presented.
Time Frame Baseline (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab and had data available for baseline antibody analysis.
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Overall Number of Participants Analyzed 35 29
Measure Type: Count of Participants
Unit of Measure: Participants
14
  40.0%
6
  20.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1128
Comments [Not Specified]
Method exact Pearson chi-square test
Comments [Not Specified]
11.Secondary Outcome
Title Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) Antibody After Induction With Treatment
Hide Description The number of participants with anti-NY-ESO-1 antibodies induced after treatment was measured using an enzyme-linked immunosorbent assay (ELISA) with recombinant NY-ESO1protein. A titer of >1:100 was considered positive. The induction of anti-NY-ESO-1 antibody response was defined as a ≥4-fold increase in the titer or the presence of a newly positive response after the first dose of treatment. The number of participants that were anti-NY-ESO-1 antibody positive after induction with treatment is presented.
Time Frame Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab and had data available for induction after treatment antibody analysis.
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Overall Number of Participants Analyzed 32 27
Measure Type: Count of Participants
Unit of Measure: Participants
16
  50.0%
0
   0.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method exact Pearson chi-square test
Comments [Not Specified]
12.Secondary Outcome
Title Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) T Cells at Baseline
Hide Description Anti-NY-ESO-1 CD4 and CD8 positive T-cell responses were measured by interferon gamma detecting enzyme-linked ImmunoSpot (ELISPOT) using isolated CD4 and CD8 positive T cells from peripheral blood mononuclear cells (PBMCs) expanded in vitro with a NY-ESO-1 peptide pool (20-mer peptides, 10-mer overlap) and considered positive if there were >50 spot-forming units/50,000 cells observed for NY-ESO-1 peptides and a ≥2-fold increase in spot-forming units compared with a negative control. The number of participants that were anti-NY-ESO-1 T cell positive at baseline is presented.
Time Frame Baseline (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab and had data available for baseline T cell analysis.
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Overall Number of Participants Analyzed 27 24
Measure Type: Count of Participants
Unit of Measure: Participants
17
  63.0%
12
  50.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4050
Comments [Not Specified]
Method exact Pearson chi-square test
Comments [Not Specified]
13.Secondary Outcome
Title Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) T Cells After Induction With Treatment
Hide Description Anti-NY-ESO-1 CD4 and CD8 positive T-cell responses were measured by interferon gamma detecting enzyme-linked ImmunoSpot (ELISPOT) using isolated CD4 and CD8 positive T cells expanded with a NY-ESO-1 peptide (20-mer peptides, 10-mer overlap) and considered positive if there were >50 spot-forming units (SPU)/50,000 cells observed for NY-ESO-1 peptides and a ≥2-fold increase in SPU compared with a negative control. The induction of an anti-NYESO-1 CD4 or CD8 positive T-cell response was defined as de novo positive or ≥2-fold rise in the number of SPU after the first dose. A fluorescence-activated cell sorting (FACS)-based intracellular cytokine staining assay for interferon gamma or tumor necrosis factor alpha after stimulation with NY-ESO-1 peptide was also used and staining ≥2-fold above the baseline value was considered positive for T-cell responses. The number of participants that were anti-NY-ESO-1 T cell positive after induction with treatment is presented.
Time Frame Up to approximately 24 months
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Hide Analysis Population Description
The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab and had data available for induction after treatment T cell analysis.
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Overall Number of Participants Analyzed 26 20
Measure Type: Count of Participants
Unit of Measure: Participants
14
  53.8%
3
  15.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0127
Comments [Not Specified]
Method exact Pearson chi-square test
Comments [Not Specified]
14.Other Pre-specified Outcome
Title Overall Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Hide Description ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all lesions in 2 consecutive observations ≥4 weeks apart) or a Partial Response (PR: ≥30% decrease in tumor burden compared with baseline in 2 observations ≥4 weeks apart) per RECIST 1.1 modified to use irRC confirmation and unidimensional tumor measurements as assessed by BICR. Participants with missing data were considered non-responders. The percentage of participants who experienced a CR or PR is presented.
Time Frame Up to approximately 36.1 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all randomized participants who met eligibility criteria for the study and had data recorded in the eCRF. Participants were included in the treatment group to which they were randomized.
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Overall Number of Participants Analyzed 45 44
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
2.2
(0.1 to 11.8)
0.0
(0.0 to 8.0)
Time Frame Up to approximately 36.1 months
Adverse Event Reporting Description Populations: All participants who received ≥1 dose of study treatment for AEs; all randomized participants for all-cause mortality. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" & "Disease progression" not related to study drug are excluded as AEs.
 
Arm/Group Title CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Hide Arm/Group Description Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein. Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
All-Cause Mortality
CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Affected / at Risk (%) Affected / at Risk (%)
Total   31/45 (68.89%)      27/44 (61.36%)    
Hide Serious Adverse Events
CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   17/45 (37.78%)      9/43 (20.93%)    
Cardiac disorders     
Acute left ventricular failure † 1  1/45 (2.22%)  2 0/43 (0.00%)  0
Atrial fibrillation † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Pericardial effusion † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Congenital, familial and genetic disorders     
Right ventricle outflow tract obstruction † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain † 1  2/45 (4.44%)  2 0/43 (0.00%)  0
Nausea † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Small intestinal haemorrhage † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
General disorders     
Chest pain † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Influenza like illness † 1  1/45 (2.22%)  1 1/43 (2.33%)  1
Pyrexia † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Immune system disorders     
Drug hypersensitivity † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Infections and infestations     
Influenza † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Pneumonia † 1  3/45 (6.67%)  3 0/43 (0.00%)  0
Pyelonephritis † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Sepsis † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Staphylococcal bacteraemia † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Urinary tract infection † 1  0/45 (0.00%)  0 1/43 (2.33%)  1
Injury, poisoning and procedural complications     
Spinal compression fracture † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Metabolism and nutrition disorders     
Hypervolaemia † 1  0/45 (0.00%)  0 1/43 (2.33%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour haemorrhage † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Nervous system disorders     
Hypoaesthesia † 1  0/45 (0.00%)  0 1/43 (2.33%)  1
Spinal cord compression † 1  0/45 (0.00%)  0 4/43 (9.30%)  4
Renal and urinary disorders     
Urinary tract obstruction † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Dyspnoea † 1  1/45 (2.22%)  1 1/43 (2.33%)  1
Haemoptysis † 1  3/45 (6.67%)  3 1/43 (2.33%)  1
Pneumonia aspiration † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Pneumonitis † 1  2/45 (4.44%)  3 0/43 (0.00%)  0
Pneumothorax † 1  1/45 (2.22%)  2 0/43 (0.00%)  0
Respiratory failure † 1  1/45 (2.22%)  1 0/43 (0.00%)  0
Skin and subcutaneous tissue disorders     
Skin ulcer † 1  0/45 (0.00%)  0 1/43 (2.33%)  1
1
Term from vocabulary, MedDRA 21.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab Atezolizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   42/45 (93.33%)      42/43 (97.67%)    
Blood and lymphatic system disorders     
Anaemia † 1  4/45 (8.89%)  6 6/43 (13.95%)  7
Lymphadenopathy † 1  3/45 (6.67%)  3 0/43 (0.00%)  0
Cardiac disorders     
Sinus tachycardia † 1  3/45 (6.67%)  3 1/43 (2.33%)  1
Gastrointestinal disorders     
Constipation † 1  9/45 (20.00%)  10 5/43 (11.63%)  6
Diarrhoea † 1  12/45 (26.67%)  15 7/43 (16.28%)  11
Nausea † 1  12/45 (26.67%)  15 11/43 (25.58%)  12
Vomiting † 1  5/45 (11.11%)  7 7/43 (16.28%)  7
General disorders     
Chest pain † 1  4/45 (8.89%)  4 2/43 (4.65%)  2
Chills † 1  3/45 (6.67%)  3 2/43 (4.65%)  2
Fatigue † 1  18/45 (40.00%)  31 10/43 (23.26%)  11
Influenza like illness † 1  3/45 (6.67%)  4 3/43 (6.98%)  4
Injection site pain † 1  5/45 (11.11%)  5 0/43 (0.00%)  0
Injection site reaction † 1  3/45 (6.67%)  3 0/43 (0.00%)  0
Pyrexia † 1  7/45 (15.56%)  8 6/43 (13.95%)  7
Infections and infestations     
Upper respiratory tract infection † 1  3/45 (6.67%)  3 2/43 (4.65%)  2
Urinary tract infection † 1  3/45 (6.67%)  3 0/43 (0.00%)  0
Injury, poisoning and procedural complications     
Procedural pain † 1  2/45 (4.44%)  2 6/43 (13.95%)  7
Investigations     
Activated partial thromboplastin time prolonged † 1  4/45 (8.89%)  10 3/43 (6.98%)  3
Alanine aminotransferase increased † 1  3/45 (6.67%)  5 4/43 (9.30%)  5
Aspartate aminotransferase increased † 1  3/45 (6.67%)  6 3/43 (6.98%)  3
Blood alkaline phosphatase increased † 1  4/45 (8.89%)  9 4/43 (9.30%)  5
Blood lactate dehydrogenase increased † 1  3/45 (6.67%)  3 2/43 (4.65%)  2
Metabolism and nutrition disorders     
Decreased appetite † 1  6/45 (13.33%)  8 2/43 (4.65%)  3
Hyperglycaemia † 1  3/45 (6.67%)  4 5/43 (11.63%)  7
Hypocalcaemia † 1  4/45 (8.89%)  6 2/43 (4.65%)  2
Hypokalaemia † 1  4/45 (8.89%)  9 3/43 (6.98%)  3
Hyponatraemia † 1  0/45 (0.00%)  0 3/43 (6.98%)  4
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  4/45 (8.89%)  4 6/43 (13.95%)  7
Back pain † 1  9/45 (20.00%)  12 4/43 (9.30%)  5
Musculoskeletal pain † 1  0/45 (0.00%)  0 3/43 (6.98%)  3
Neck pain † 1  3/45 (6.67%)  3 2/43 (4.65%)  4
Pain in extremity † 1  5/45 (11.11%)  5 6/43 (13.95%)  8
Nervous system disorders     
Headache † 1  6/45 (13.33%)  7 7/43 (16.28%)  7
Neuralgia † 1  1/45 (2.22%)  1 4/43 (9.30%)  4
Psychiatric disorders     
Insomnia † 1  4/45 (8.89%)  4 3/43 (6.98%)  3
Renal and urinary disorders     
Acute kidney injury † 1  3/45 (6.67%)  3 0/43 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Cough † 1  8/45 (17.78%)  11 5/43 (11.63%)  6
Dyspnoea † 1  12/45 (26.67%)  15 3/43 (6.98%)  3
Haemoptysis † 1  5/45 (11.11%)  6 2/43 (4.65%)  3
Oropharyngeal pain † 1  3/45 (6.67%)  3 1/43 (2.33%)  1
Pleuritic pain † 1  3/45 (6.67%)  3 0/43 (0.00%)  0
Pneumothorax † 1  0/45 (0.00%)  0 3/43 (6.98%)  3
Skin and subcutaneous tissue disorders     
Dry skin † 1  6/45 (13.33%)  6 0/43 (0.00%)  0
Pruritus † 1  5/45 (11.11%)  6 2/43 (4.65%)  2
Rash pruritic † 1  1/45 (2.22%)  1 3/43 (6.98%)  3
Vascular disorders     
Hypertension † 1  5/45 (11.11%)  8 5/43 (11.63%)  5
1
Term from vocabulary, MedDRA 21.1
†
Indicates events were collected by systematic assessment
[Not Specified]
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.
Manuscripts reporting the results of this clinical trial, abstracts, press releases, and other media presentations must be provided to the Sponsor for review and comment 30 days prior to submission for publication and may be delayed for up to an additional 30 days in order to ensure that confidential and proprietary data, and intellectual property rights, are protected. Co-authorship of publications will be discussed and mutually agreed upon before submission of a manuscript to a publisher.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Immune Design
ClinicalTrials.gov Identifier: NCT02609984    
Other Study ID Numbers: IMDZ-C232
V943A-002 ( Other Identifier: Merck )
IMDZ-C232 ( Other Identifier: Immune Design )
First Submitted: November 14, 2015
First Posted: November 20, 2015
Results First Submitted: April 30, 2020
Results First Posted: May 14, 2020
Last Update Posted: July 7, 2020