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Phase Ib/II Study of MEDI4736 Evaluated in Different Combinations in Metastatic Pancreatic Ductal Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02583477
Recruitment Status : Completed
First Posted : October 22, 2015
Results First Posted : August 14, 2019
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Pancreatic Ductal Adenocarcinoma
Interventions Drug: MEDI4736 in combination with nab-paclitaxel and gemcitabine
Drug: MEDI4736 in combination with AZD5069
Enrollment 23
Recruitment Details This study consisted of 2 independent cohorts, each of which ran at separate times between 25 March 2016 and 09 July 2018. In Cohort 1, participants were recruited from 1 center in the United States; in Cohort 2, participants were recruited from 6 centers in the United Kingdom.
Pre-assignment Details Participants underwent screening evaluations to determine eligibility within 4 weeks (28 days) prior to first administration of the Investigational Product (IP). A total of 27 participants (3 in Cohort 1 and 24 in Cohort 2) were assigned to treatment and 23 were treated. Only treated participants are included in the participant flow.
Arm/Group Title Cohort 1 (MEDI4736 + Nab-paclitaxel + Gemcitabine) Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description Participants with metastatic pancreatic ductal adenocarcinoma (PDAC) who were treatment naive received MEDI4736 1.5 gram (g) intravenous (IV) infusion on Day 1 of each 28-day cycle (q4w). Participants also received nab-paclitaxel 125 milligram per meter square (mg/m^2) IV infusion followed by gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28-day cycle. Treatment continued until either confirmed progressive disease (PD) unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally twice daily (bid). The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Period Title: Overall Study
Started 3 20
Received Treatment 3 20
Completed Treatment 0 0
Completed [1] 0 0
Not Completed 3 20
Reason Not Completed
Adverse Event             0             2
Death             1             16
Study terminated             2             2
[1]
Completed study
Arm/Group Title Cohort 1 (MEDI4736 + Nab-paclitaxel + Gemcitabine) Cohort 2 (MEDI4736 + AZD5069) Total
Hide Arm/Group Description Participants with metastatic PDAC who were treatment naive received MEDI4736 1.5 g IV infusion q4w. Participants also received nab-paclitaxel 125 mg/m^2 IV infusion followed by gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28-day cycle. Treatment continued until either confirmed PD unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Total of all reporting groups
Overall Number of Baseline Participants 3 20 23
Hide Baseline Analysis Population Description
The safety analysis set included all participants who received at least 1 dose of IP and for whom any post-dose data were available.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 20 participants 23 participants
<50 years
0
   0.0%
4
  20.0%
4
  17.4%
>=50 - <65 years
1
  33.3%
12
  60.0%
13
  56.5%
>=65 - <75 years
2
  66.7%
4
  20.0%
6
  26.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 20 participants 23 participants
Female
2
  66.7%
9
  45.0%
11
  47.8%
Male
1
  33.3%
11
  55.0%
12
  52.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 20 participants 23 participants
Asian
0
   0.0%
1
   5.0%
1
   4.3%
White
3
 100.0%
18
  90.0%
21
  91.3%
Other
0
   0.0%
1
   5.0%
1
   4.3%
1.Primary Outcome
Title Number of Participants With Dose-Limiting Toxicities (DLT)
Hide Description

DLT period was defined as first treatment cycle for Cohort 1, and first dose of AZD5069 and MEDI4736 to end of Cycle 1 or until a participant experienced a DLT, whichever occurs first for Cohort 2.

A DLT was defined as any of below listed laboratory abnormalities or adverse events (AE) related to MEDI4736 collected during DLT period.

  • Liver transaminase elevation >= 5× but <= 8× upper limit of normal (ULN) that doesn't resolve to Grade 2 within 5 days
  • Transaminase elevation > 8× ULN or total bilirubin > 5× ULN
  • Any Grade 4 immune-related AE (irAE) not attributed to local tumor response, Grade >=3 colitis, Grade >=2 pneumonitis that doesn't resolve to <= Grade 1 within 7 days, Grade 3 irAE, that doesn't resolve to Grade <=1 or baseline status within 14 days
  • Any Grade >=3 non-irAE toxicity that doesn't resolve to Grade <=1 or baseline status within 14 days A DLT was defined as any Grade 3 or worse AE related to AZD5069 that occurs from first dose of AZD5069 up to end of DLT period.
Time Frame Cohort 1: From time of first dose of MEDI4736 on Day 1 up to Day 28 of Cycle 1 and Cohort 2: From time of first dose of AZD5069 and MEDI4736 on Day 1 up to Day 28 of Cycle 1 or until a participant experiences a DLT, whichever occurs first.
Hide Outcome Measure Data
Hide Analysis Population Description

For Cohort 1: Participants who completed DLT evaluation period and/or discontinued study treatment early due to a DLT and who have not missed >=2 infusions of gemcitabine.

For Cohort 2: Participants who received 50% of planned doses of AZD5069 during DLT period as well as MEDI4736 infusion and remained active on study at end of Day 28 of Cycle 1.

Arm/Group Title Cohort 1 (MEDI4736 + Nab-paclitaxel + Gemcitabine) Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description:
Participants with metastatic PDAC who were treatment naive received MEDI4736 1.5 g IV infusion q4w. Participants also received nab-paclitaxel 125 mg/m^2 IV infusion followed by gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28-day cycle. Treatment continued until either confirmed PD unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed 3 12
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
4
  33.3%
2.Primary Outcome
Title Number of Participants With AEs
Hide Description An AE is the development of an undesirable medical condition or deterioration of a pre-existing medical condition following or during exposure to study treatment, whether or not considered causally related to study treatment. An undesirable medical condition can be symptoms, signs or abnormal results of an investigation. A serious AE (SAE) is an AE that fulfills one or more following criteria: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity or substantial disruption of ability to conduct normal life functions, congenital abnormality or birth defect, and an important medical event that may jeopardize participant or may require medical intervention to prevent one of outcomes listed above. AEs leading to discontinuation of study treatment were those with action taken was 'Drug Permanently Discontinued' for any study treatment. Only treatment emergent AEs were presented.
Time Frame From first dose of study treatment administration (Day 1) until 90 days after the last dose of IP or initiation of the first subsequent anticancer therapy (whichever occurred first), approximately 30 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants who received at least 1 dose of IP and for whom any post-dose data were available.
Arm/Group Title Cohort 1 (MEDI4736 + Nab-paclitaxel + Gemcitabine) Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description:
Participants with metastatic PDAC who were treatment naive received MEDI4736 1.5 g IV infusion q4w. Participants also received nab-paclitaxel 125 mg/m^2 IV infusion followed by gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28-day cycle. Treatment continued until either confirmed PD unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed 3 20
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
3
 100.0%
20
 100.0%
Any AE causally related to treatment (CRT)
3
 100.0%
14
  70.0%
Any AE of CTCAE Grade 3 or higher
3
 100.0%
18
  90.0%
Any AE of CTCAE Grade 3 or higher CRT
3
 100.0%
10
  50.0%
Any AE leading discontinuation of study treatment
2
  66.7%
3
  15.0%
Any AE with outcome of death
1
  33.3%
4
  20.0%
Any AE with outcome of death CRT
1
  33.3%
0
   0.0%
Any SAE
1
  33.3%
16
  80.0%
Any SAE CRT
1
  33.3%
8
  40.0%
3.Primary Outcome
Title Objective Response Rate (ORR) in Cohort 2
Hide Description ORR is defined as the percentage of participants with a confirmed overall response of complete response (CR) or partial response (PR). A confirmed response of CR/PR means that a response of CR/PR is recorded at 1 visit and confirmed by repeat imaging, preferably at the next regularly scheduled imaging visit and not less than 4 weeks after the visit when the response was first observed with no evidence of progression between the initial and CR/PR confirmation visit. CR is defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of TLs, taking as reference the baseline sum of diameters as long as criteria for PD were not met. ORR was determined using Investigator assessments according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1).
Time Frame RECIST assessments performed at baseline (within 28 days before start of study treatment), every 6 weeks +/-7 days for first 48 weeks, then every 12 weeks +/-7 days thereafter until confirmed objective disease progression. Up to approximately 30 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set included all participants who received at least 1 dose of IP and with no important protocol deviation that could impact the efficacy evaluation.
Arm/Group Title Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description:
Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed 18
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: percentage of participants
5.6
(0.58 to 19.95)
4.Secondary Outcome
Title Duration of Response (DoR) in Cohort 2
Hide Description DoR was defined as the time from the first documentation of CR/PR (which is subsequently confirmed) until the date of progression/death, or the last evaluable RECIST assessment for participants that did not progress or did progress after 2 missed visits of the last evaluable assessment (or first dose). PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. DoR was determined using Investigator assessments according to RECIST v1.1 and was calculated using the Kaplan-Meier technique.
Time Frame RECIST assessments performed at baseline (within 28 days before start of study treatment), every 6 weeks +/-7 days for first 48 weeks, then every 12 weeks +/-7 days thereafter until confirmed objective disease progression. Up to approximately 30 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set included all participants who received at least 1 dose of IP and with no important protocol deviation that could impact the efficacy evaluation. Participants with confirmed response were evaluated, only one participant showed response.
Arm/Group Title Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description:
Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed 1
Median (Inter-Quartile Range)
Unit of Measure: weeks
18.29
(18.29 to 18.29)
5.Secondary Outcome
Title Disease Control Rate (DCR) in Cohort 2
Hide Description DCR at 6 months is defined as the percentage of participants who had a best objective response (BoR) of CR or PR in the first 6 months (i.e. 24+1=25 weeks to allow for a late assessment within the assessment window) or who had demonstrated stable disease (SD) for a minimum interval of 24 weeks (minus 1 week to allow for an early assessment within the assessment window, i.e. 161 days) following the start of treatment. DCR at 12 months is defined as the percentage of participants who had a BoR of CR or PR in the first 12 months (i.e. 48+1=49 weeks to allow for a late assessment within the assessment window) or who had demonstrated SD for a minimum interval of 48 weeks (minus 1 week to allow for an early assessment within the assessment window, i.e. 329 days) following the start of treatment. DCR was determined using Investigator assessments according to RECIST v1.1.
Time Frame RECIST assessments were performed at baseline (within 28 days before start of study treatment) and every 6 weeks +/- 7 days for first 48 weeks up to 6 months and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set included all participants who received at least 1 dose of IP and with no important protocol deviation that could impact the efficacy evaluation.
Arm/Group Title Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description:
Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: percentage of participants
At 6 months 11.1
At 12 months 5.6
6.Secondary Outcome
Title Median Progression-Free Survival (PFS) in Cohort 2
Hide Description PFS is defined as the time from the date of first dose until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraws from allocated therapy or receives another anticancer therapy prior to progression. PFS was determined using Investigator assessments according to RECIST v1.1 and calculated using the Kaplan-Meier technique.
Time Frame RECIST assessments performed at baseline (within 28 days before start of study treatment), every 6 weeks +/-7 days for first 48 weeks, then every 12 weeks +/-7 days thereafter until confirmed objective disease progression. Up to approximately 30 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set included all participants who received at least 1 dose of IP and with no important protocol deviation that could impact the efficacy evaluation.
Arm/Group Title Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description:
Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed 18
Median (95% Confidence Interval)
Unit of Measure: months
1.6
(1.29 to 1.68)
7.Secondary Outcome
Title Progression-Free Survival Rate at 3 Months (PFS3) in Cohort 2
Hide Description The PFS rate was defined as percentage of participants alive and progression-free after 3 months. The PFS3 was calculated using Kaplan-Meier estimates. Tumor progression was determined based on Investigator assessment and RECIST v1.1.
Time Frame RECIST assessments were performed at baseline (within 28 days before start of study treatment) and every 6 weeks +/- 7 days up to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set included all participants who received at least 1 dose of IP and with no important protocol deviation that could impact the efficacy evaluation.
Arm/Group Title Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description:
Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed 18
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: percentage of participants
11.1
(3.91 to 22.55)
8.Secondary Outcome
Title Progression-Free Survival Rate at 6 Months (PFS6) in Cohort 2
Hide Description The PFS6 was defined as percentage of participants alive and progression-free after 6 months. The PFS6 was calculated using Kaplan-Meier estimates. Tumor progression was determined based on Investigator assessment and RECIST v1.1.
Time Frame RECIST assessments were performed at baseline (within 28 days before start of study treatment) and every 6 weeks +/- 7 days up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set included all participants who received at least 1 dose of IP and with no important protocol deviation that could impact the efficacy evaluation.
Arm/Group Title Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description:
Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed 18
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: percentage of participants
11.1
(3.91 to 22.55)
9.Secondary Outcome
Title Median Overall Survival (OS) in Cohort 2
Hide Description OS is defined as the time from the date of first dose until death due to any cause (i.e. date of death or censoring - date of first dose + 1). OS was calculated using the Kaplan-Meier technique. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive (censored at end of study).
Time Frame RECIST assessments performed at baseline (within 28 days before start of study treatment), every 6 weeks +/-7 days for first 48 weeks, then every 12 weeks +/-7 days thereafter until confirmed objective disease progression. Up to approximately 30 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set included all participants who received at least 1 dose of IP and with no important protocol deviation that could impact the efficacy evaluation.
Arm/Group Title Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description:
Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed 18
Median (95% Confidence Interval)
Unit of Measure: months
2.8
(1.68 to 3.79)
10.Secondary Outcome
Title Overall Survival at 6 Months (OS6) in Cohort 2
Hide Description OS6 is defined as percentage of participants alive at 6 months from first dose of study treatment. OS6 was calculated using the Kaplan-Meier estimate of OS at 6 months.
Time Frame From first dose of study treatment (Day 1) up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set included all participants who received at least 1 dose of IP and with no important protocol deviation that could impact the efficacy evaluation.
Arm/Group Title Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description:
Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed 18
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: percentage of participants
22.2
(11.19 to 35.59)
11.Secondary Outcome
Title Overall Survival at 12 Months (OS12) in Cohort 2
Hide Description OS12 is defined as percentage of participants alive at 12 months from first dose of study treatment. OS12 was calculated using the Kaplan-Meier estimate of OS at 12 months.
Time Frame From first dose of study treatment (Day 1) up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set included all participants who received at least 1 dose of IP and with no important protocol deviation that could impact the efficacy evaluation.
Arm/Group Title Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description:
Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed 18
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: percentage of participants
14.8
(5.74 to 27.92)
12.Secondary Outcome
Title Number of Participants With Anti-Drug Antibody (ADAs) for MEDI4736 in Cohort 2
Hide Description Samples were measured for the presence of ADAs and ADA-neutralizing antibodies for MEDI4736 using validated assays. Persistently positive is defined as positive at >=2 post-baseline assessments or positive at the last post-baseline assessment. Transiently positive is defined as having at least one post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. NAB = neutralizing antibody.
Time Frame On Day 1 of Cycles 1, 2, 3, 4, and 7; At months 3 and 6 after last dose
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants who received at least 1 dose of IP and for whom any post-dose data were available.
Arm/Group Title Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description:
Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed 20
Measure Type: Count of Participants
Unit of Measure: Participants
Positive at any visit
3
  15.0%
Both baseline and post-baseline positive
0
   0.0%
Only post-baseline positive
1
   5.0%
Only baseline positive
2
  10.0%
ADA persistently positive
0
   0.0%
ADA transiently positive
1
   5.0%
ADA positive participants who are NAB positive
0
   0.0%
13.Secondary Outcome
Title Mean Plasma Concentrations of MEDI4736 in Cohort 2
Hide Description Mean peak and trough plasma concentrations of MEDI4736 are presented.
Time Frame Predose (within 60 minutes prior to treatment with any IP) on Day 1 of Cycles 1, 2, 3, 4, and 7; and post infusion (within 10 minutes after end of MEDI4736 infusion) on Day 1 of Cycles 1 and 7
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of IP per protocol for whom any post-dose data were available and who did not violate or deviate from the protocol in ways that would significantly affect the PK analyses.
Arm/Group Title Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description:
Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter
Cycle 1 Day 1: Predose Number Analyzed 2 participants
1444.730  (1010.7667)
Cycle 1 Day 1: Post infusion Number Analyzed 20 participants
339342.229  (95923.6405)
Cycle 2 Day 1: Predose Number Analyzed 11 participants
56773.555  (17716.8788)
Cycle 3 Day 1: Predose Number Analyzed 6 participants
63655.840  (26425.8402)
Cycle 4 Day 1: Predose Number Analyzed 4 participants
69325.233  (22750.3387)
Cycle 7 Day 1: Predose Number Analyzed 1 participants
79687.820 [1]   (NA)
Cycle 7 Day 1: Post infusion Number Analyzed 1 participants
435297.610 [1]   (NA)
[1]
Standard deviation cannot be calculated when only one participant analyzed.
14.Secondary Outcome
Title Mean Plasma Concentrations of AZD5069 in Cohort 2
Hide Description Mean peak and trough plasma concentration of AZD5069 are presented. Concentration of AZD5069 was calculated by plasma concentration-time profile.
Time Frame Predose (within 60 minutes prior to treatment with any IP) on Day 1 of Cycles 1, 2, 3, 4, and 7; and postdose (within 10 minutes after end of MEDI4736 infusion) on Day 1 of Cycles 1, 2, and 7
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set included all participants who received at least 1 dose of IP per protocol for whom any post-dose data were available and who did not violate or deviate from the protocol in ways that would significantly affect the PK analyses.
Arm/Group Title Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description:
Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: nanomoles per liter
Cycle 1 Day 1: Predose Number Analyzed 20 participants
10.60  (42.933)
Cycle 1 Day 1: Postdose Number Analyzed 19 participants
2236.29  (1678.496)
Cycle 2 Day 1: Predose Number Analyzed 11 participants
1829.36  (1473.533)
Cycle 2 Day 1: Postdose Number Analyzed 1 participants
24.40 [1]   (NA)
Cycle 3 Day 1: Predose Number Analyzed 5 participants
502.48  (601.914)
Cycle 4 Day 1: Predose Number Analyzed 4 participants
1345.00  (1068.666)
Cycle 7 Day 1: Predose Number Analyzed 1 participants
1200.00 [1]   (NA)
Cycle 7 Day 1: Postdose Number Analyzed 1 participants
7540.00 [1]   (NA)
[1]
Standard deviation cannot be calculated when only one participant analyzed.
Time Frame From initial IP administration (Day 1) until 90 days after the last dose of IP or initiation of the first subsequent anticancer therapy (whichever occurred first), approximately 30 months.
Adverse Event Reporting Description The safety analysis set included all participants who received at least 1 dose of IP and for whom any post-dose data were available.
 
Arm/Group Title Cohort 1 (MEDI4736 + Nab-paclitaxel + Gemcitabine) Cohort 2 (MEDI4736 + AZD5069)
Hide Arm/Group Description Participants with metastatic PDAC who were treatment naive received MEDI4736 1.5 g IV infusion q4w. Participants also received nab-paclitaxel 125 mg/m^2 IV infusion followed by gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28-day cycle. Treatment continued until either confirmed PD unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Participants with metastatic PDAC with progression on the indicated types of chemotherapy received MEDI4736 1.5 g IV infusion q4w. Participants also received AZD5069 orally bid. The starting dose of 80 mg orally bid (with dose reductions to 40 mg or 20 mg for toxicity allowable). Treatment continued until either confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
All-Cause Mortality
Cohort 1 (MEDI4736 + Nab-paclitaxel + Gemcitabine) Cohort 2 (MEDI4736 + AZD5069)
Affected / at Risk (%) Affected / at Risk (%)
Total   1/3 (33.33%)      16/20 (80.00%)    
Hide Serious Adverse Events
Cohort 1 (MEDI4736 + Nab-paclitaxel + Gemcitabine) Cohort 2 (MEDI4736 + AZD5069)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/3 (33.33%)      16/20 (80.00%)    
Blood and lymphatic system disorders     
Febrile neutropenia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Gastrointestinal disorders     
Constipation  1  1/3 (33.33%)  1 1/20 (5.00%)  1
Diarrhoea  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Enterocolitis  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Gastric haemorrhage  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Nausea  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Obstruction gastric  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Upper gastrointestinal haemorrhage  1  0/3 (0.00%)  0 1/20 (5.00%)  3
Vomiting  1  0/3 (0.00%)  0 2/20 (10.00%)  2
General disorders     
General physical health deterioration  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Pyrexia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Hepatobiliary disorders     
Cholangitis  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Drug-induced liver injury  1  1/3 (33.33%)  1 0/20 (0.00%)  0
Hepatic failure  1  1/3 (33.33%)  1 0/20 (0.00%)  0
Hepatitis  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Infections and infestations     
Biliary sepsis  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Lower respiratory tract infection  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Neutropenic sepsis  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Pneumonia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Streptococcal sepsis  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Viral infection  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Injury, poisoning and procedural complications     
Infusion related reaction  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Investigations     
Neutrophil count decreased  1  0/3 (0.00%)  0 1/20 (5.00%)  3
Metabolism and nutrition disorders     
Hypovolaemia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  1/3 (33.33%)  1 0/20 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Nervous system disorders     
Ischaemic stroke  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Pleural effusion  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Pneumonitis  1  1/3 (33.33%)  1 1/20 (5.00%)  1
Pulmonary embolism  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Pulmonary oedema  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Vascular disorders     
Embolism  1  0/3 (0.00%)  0 1/20 (5.00%)  1
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort 1 (MEDI4736 + Nab-paclitaxel + Gemcitabine) Cohort 2 (MEDI4736 + AZD5069)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      20/20 (100.00%)    
Blood and lymphatic system disorders     
Anaemia  1  1/3 (33.33%)  1 1/20 (5.00%)  1
Leukopenia  1  1/3 (33.33%)  2 0/20 (0.00%)  0
Neutropenia  1  2/3 (66.67%)  6 2/20 (10.00%)  2
Cardiac disorders     
Sinus tachycardia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Tachycardia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Ventricular extrasystoles  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Endocrine disorders     
Hypothyroidism  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Eye disorders     
Blindness unilateral  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Gastrointestinal disorders     
Abdominal distension  1  1/3 (33.33%)  1 2/20 (10.00%)  3
Abdominal pain  1  0/3 (0.00%)  0 6/20 (30.00%)  7
Abdominal pain upper  1  0/3 (0.00%)  0 3/20 (15.00%)  3
Aptyalism  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Ascites  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Colitis  1  1/3 (33.33%)  1 0/20 (0.00%)  0
Constipation  1  0/3 (0.00%)  0 4/20 (20.00%)  5
Diarrhoea  1  2/3 (66.67%)  2 4/20 (20.00%)  7
Dry mouth  1  0/3 (0.00%)  0 2/20 (10.00%)  2
Dyspepsia  1  0/3 (0.00%)  0 3/20 (15.00%)  3
Glossodynia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Melaena  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Nausea  1  1/3 (33.33%)  1 8/20 (40.00%)  10
Parotid gland enlargement  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Peptic ulcer  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Rectal discharge  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Steatorrhoea  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Stomatitis  1  0/3 (0.00%)  0 5/20 (25.00%)  5
Tongue coated  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Vomiting  1  1/3 (33.33%)  1 2/20 (10.00%)  10
General disorders     
Administration site mass  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Chills  1  1/3 (33.33%)  2 0/20 (0.00%)  0
Fatigue  1  2/3 (66.67%)  2 10/20 (50.00%)  11
Oedema peripheral  1  1/3 (33.33%)  1 2/20 (10.00%)  2
Pain  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Peripheral swelling  1  0/3 (0.00%)  0 2/20 (10.00%)  2
Pyrexia  1  1/3 (33.33%)  1 1/20 (5.00%)  5
Hepatobiliary disorders     
Hyperbilirubinaemia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Infections and infestations     
Cellulitis  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Escherichia urinary tract infection  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Lower respiratory tract infection viral  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Nasopharyngitis  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Oral candidiasis  1  0/3 (0.00%)  0 5/20 (25.00%)  5
Pneumonia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Skin infection  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Upper respiratory tract infection  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Urinary tract infection  1  1/3 (33.33%)  1 0/20 (0.00%)  0
Injury, poisoning and procedural complications     
Contusion  1  0/3 (0.00%)  0 2/20 (10.00%)  3
Fall  1  0/3 (0.00%)  0 3/20 (15.00%)  3
Skin wound  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Soft tissue injury  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Investigations     
Blood alkaline phosphatase increased  1  0/3 (0.00%)  0 1/20 (5.00%)  3
Blood bicarbonate decreased  1  0/3 (0.00%)  0 1/20 (5.00%)  4
Blood creatinine increased  1  1/3 (33.33%)  1 0/20 (0.00%)  0
Blood glucose increased  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Blood thyroid stimulating hormone increased  1  0/3 (0.00%)  0 1/20 (5.00%)  2
Body temperature increased  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Citrobacter test positive  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Electrocardiogram QT prolonged  1  0/3 (0.00%)  0 1/20 (5.00%)  2
Gamma-glutamyltransferase increased  1  0/3 (0.00%)  0 1/20 (5.00%)  3
Lymphocyte count decreased  1  0/3 (0.00%)  0 2/20 (10.00%)  3
Neutrophil count decreased  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Prothrombin time prolonged  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Weight decreased  1  0/3 (0.00%)  0 3/20 (15.00%)  4
Metabolism and nutrition disorders     
Decreased appetite  1  1/3 (33.33%)  2 7/20 (35.00%)  8
Diabetes mellitus  1  1/3 (33.33%)  1 0/20 (0.00%)  0
Hypercalcaemia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Hyperglycaemia  1  0/3 (0.00%)  0 2/20 (10.00%)  2
Hypoalbuminaemia  1  0/3 (0.00%)  0 2/20 (10.00%)  5
Hypocalcaemia  1  1/3 (33.33%)  1 0/20 (0.00%)  0
Hypokalaemia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Hyponatraemia  1  1/3 (33.33%)  1 1/20 (5.00%)  2
Iron deficiency  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Back pain  1  0/3 (0.00%)  0 2/20 (10.00%)  2
Muscle spasms  1  1/3 (33.33%)  2 0/20 (0.00%)  0
Musculoskeletal chest pain  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Musculoskeletal pain  1  0/3 (0.00%)  0 3/20 (15.00%)  3
Myalgia  1  1/3 (33.33%)  1 1/20 (5.00%)  1
Pain in extremity  1  0/3 (0.00%)  0 2/20 (10.00%)  2
Temporomandibular joint syndrome  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain  1  0/3 (0.00%)  0 2/20 (10.00%)  2
Tumour associated fever  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Nervous system disorders     
Disturbance in attention  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Dizziness  1  0/3 (0.00%)  0 2/20 (10.00%)  2
Dysgeusia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Headache  1  1/3 (33.33%)  1 0/20 (0.00%)  0
Hypoaesthesia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Lethargy  1  0/3 (0.00%)  0 3/20 (15.00%)  3
Paraesthesia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Somnolence  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Psychiatric disorders     
Anxiety  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Confusional state  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Depressed mood  1  0/3 (0.00%)  0 2/20 (10.00%)  2
Depression  1  0/3 (0.00%)  0 2/20 (10.00%)  3
Insomnia  1  1/3 (33.33%)  1 0/20 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Haematuria  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Pollakiuria  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Polyuria  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Respiratory, thoracic and mediastinal disorders     
Atelectasis  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Cough  1  0/3 (0.00%)  0 2/20 (10.00%)  3
Dysphonia  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Dyspnoea  1  0/3 (0.00%)  0 2/20 (10.00%)  2
Oropharyngeal pain  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Pulmonary embolism  1  0/3 (0.00%)  0 3/20 (15.00%)  3
Skin and subcutaneous tissue disorders     
Alopecia  1  2/3 (66.67%)  2 1/20 (5.00%)  1
Night sweats  1  0/3 (0.00%)  0 2/20 (10.00%)  2
Pruritus  1  1/3 (33.33%)  1 0/20 (0.00%)  0
Rash  1  1/3 (33.33%)  1 1/20 (5.00%)  1
Rash maculo-papular  1  1/3 (33.33%)  1 0/20 (0.00%)  0
Skin mass  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Vasculitic rash  1  0/3 (0.00%)  0 1/20 (5.00%)  2
Vascular disorders     
Deep vein thrombosis  1  0/3 (0.00%)  0 1/20 (5.00%)  1
Vena cava thrombosis  1  0/3 (0.00%)  0 1/20 (5.00%)  1
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Due to a programmatic decision, enrollment of additional participants to cohort 1 was not pursued. The study was terminated by sponsor.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Lead
Organization: AstraZeneca
Phone: +1 302 885 1180
EMail: ClinicalTrialTransparency@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02583477    
Other Study ID Numbers: D4198C00003
First Submitted: October 20, 2015
First Posted: October 22, 2015
Results First Submitted: May 8, 2019
Results First Posted: August 14, 2019
Last Update Posted: August 14, 2019