Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Initial Stage Cohorts: Disease Control Rate (DCR) at Week 12 |
The DCR at 12 weeks was defined as the percentage of participants who had complete response (CR) + partial response (PR) + stable disease (SD) at 12 weeks. Participants demonstrated SD for a minimum interval of 11 weeks (minus 1 week to allow for an early assessment within the assessment window, i.e. 77 days) following the start of treatment. The DCR was determined using Investigator assessments according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). |
RECIST performed at baseline, at 4 weeks after first dose of olaparib monotherapy and every 8 weeks +/-7 days thereafter. Assessed until DCO 14 Jun 2019. |
|
| Primary |
Second Stage Cohort: Objective Response Rate (ORR) |
The ORR (based on RECIST 1.1 as assessed by the Investigator) was defined as the percentage of participants with at least 1 visit response of CR or PR prior to PD or last evaluable assessment in the absence of progression. The 95% confidence interval (CI) were calculated using Exact Clopper-Pearson confidence limits for the binomial proportion. |
RECIST performed at baseline, and every 8 weeks +/-7 days thereafter. Assessed until 17 Sep 2021. |
|
| Primary |
Second Stage Cohorts: DCR at Week 24 |
The DCR at 24 weeks was defined as the percentage of participants who had CR + PR + SD at 24 weeks. Participants demonstrated SD for a minimum interval of 23 weeks (minus 1 week to allow for an early assessment within the assessment window, i.e. 161 days) following the start of treatment. The DCR was determined using Investigator assessments according to RECIST v1.1. |
RECIST performed at baseline, and every 8 weeks +/-7 days thereafter. Assessed until 17 Sep 2021. |
|
| Secondary |
Second Stage Expansion Cohort: DCR at Week 24 |
The DCR at 24 weeks was defined as the percentage of participants who had CR + PR + SD at 24 weeks. Participants demonstrated SD for a minimum interval of 23 weeks (minus 1 week to allow for an early assessment within the assessment window, i.e. 161 days) following the start of treatment. The DCR was determined using Investigator assessments according to RECIST v1.1. |
RECIST performed at baseline, and every 8 weeks +/-7 days thereafter. Assessed until 17 Sep 2021. |
|
| Secondary |
Initial Stage Cohorts: DCR at Week 28 |
The DCR at 28 weeks was defined as the percentage of participants who had CR + PR + SD at 28 weeks. Participants demonstrated SD for a minimum interval of 27 weeks (minus 1 week to allow for an early assessment within the assessment window, i.e. 189 days) following the start of treatment. The DCR was determined using Investigator assessments according to RECIST v1.1. |
RECIST performed at baseline, at 4 weeks after first dose of olaparib monotherapy and every 8 weeks +/-7 days thereafter. Assessed until DCO 14 Jun 2019. |
|
| Secondary |
Second Stage Cohorts: DCR at Week 56 |
The DCR at 56 weeks was defined as the percentage of participants who had CR + PR + SD at 56 weeks. Participants demonstrated SD for a minimum interval of 55 weeks (minus 1 week to allow for an early assessment within the assessment window, i.e. 385 days) following the start of treatment. The DCR was determined using Investigator assessments according to RECIST v1.1. |
RECIST performed at baseline, and every 8 weeks +/-7 days thereafter. Assessed until 17 Sep 2021. |
|
| Secondary |
Initial and Second Stage Cohorts: ORR |
The ORR (based on RECIST 1.1 as assessed by the Investigator) was defined as the percentage of participants with at least 1 visit response of CR or PR prior to PD or last evaluable assessment in the absence of progression. The 95% CI were calculated using Exact Clopper-Pearson confidence limits for the binomial proportion. |
RECIST performed at baseline, at 4 weeks after first dose of olaparib monotherapy (for initial stage cohort only) and every 8 weeks +/-7 days thereafter. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively |
|
| Secondary |
Initial and Second Stage Cohorts: Duration of Response (DoR) |
The DoR (based on RECIST 1.1 as assessed by the Investigator) was defined as the time from the date of first documented response until date of documented progression or death in the absence of PD. The DoR was calculated using Kaplan-Meier technique. |
RECIST performed at baseline, at 4 weeks after first dose of olaparib monotherapy (for initial stage cohort only) and every 8 weeks +/-7 days thereafter. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively |
|
| Secondary |
Initial and Second Stage Cohorts: Progression-Free Survival (PFS) |
The PFS (based on RECIST 1.1 as assessed by the Investigator) was defined as the time from start of study treatment (Day 1; start of olaparib monotherapy for initial stage cohorts) until the date of objective PD or death (by any cause in the absence of disease progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to disease progression. The PFS was calculated using Kaplan-Meier technique. |
RECIST performed at baseline, at 4 weeks after first dose of olaparib monotherapy (for initial stage cohort only) and every 8 weeks +/-7 days thereafter. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively |
|
| Secondary |
Initial Stage Cohorts: Percentage Change From Baseline in Target Tumor Size at Weeks 12 and 28 |
The percentage change in target tumor size at each timepoint (based on RECIST 1.1 target lesion measurements) was obtained for each participant taking the difference between the sum of the target lesions at each timepoint and the sum of the target lesions at baseline divided by the sum of the target lesions at baseline times 100. Baseline was defined as the last evaluable assessment prior to starting olaparib treatment. |
Baseline (Day 1) and Weeks 12 and 28. Assessed until DCO 14 Jun 2019 |
|
| Secondary |
Second Stage Cohorts: Percentage Change From Baseline in Target Tumor Size at Weeks 24 and 56 |
The percentage change in target tumor size at each timepoint (based on RECIST 1.1 target lesion measurements) was obtained for each participant taking the difference between the sum of the target lesions at each timepoint and the sum of the target lesions at baseline divided by the sum of the target lesions at baseline times 100. Baseline was defined as the last assessment prior to Cycle 1 Day 1. |
Baseline (Day 1) and Weeks 24 and 56. Assessed until DCO 17 Sep 2021 |
|
| Secondary |
Initial and Second Stage Cohorts: Best Percentage Change From Baseline in Target Tumor Size |
The best percentage change from baseline in target tumor size was based on RECIST 1.1 target lesion measurements taken at each RECIST 1.1 assessment. All measurements until PD or the last evaluable assessment in the absence of PD was included in the calculation. Baseline was defined as the last evaluable assessment prior to starting olaparib treatment for initial stage cohorts. Baseline was defined as the last assessment prior to Cycle 1 Day 1 for second stage cohorts. |
From baseline (Day 1) until confirmed PD/death. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively |
|
| Secondary |
Initial and Second Stage Cohorts: Time to Study Treatment Discontinuation or Death (TDT) |
The TDT was defined as the time from start of study treatment (Day 1; start of olaparib monotherapy for initial stage cohorts) to the earlier of the date of study treatment discontinuation or death. The TDT was calculated using the Kaplan-Meier technique. |
From baseline (Day 1) until treatment discontinuation/death. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively |
|
| Secondary |
Initial and Second Stage Cohorts: OS |
The OS was defined as the time from the start of study treatment (Day 1; start of olaparib monotherapy for initial stage cohorts) until death due to any cause. The OS was calculated using the Kaplan-Meier technique. |
From baseline (Day 1) until death from any cause. Assessed until DCO 14 Jun 2019 for initial stage cohorts except for ovarian cancer cohort and DCO 17 Sep 2021 for initial stage ovarian cancer cohort and second stage cohorts |
|
| Secondary |
Initial and Second Stage Cohorts: Serum Concentrations of MEDI4736 |
Blood samples were collected to determine the serum concentration of MEDI4736. |
Pre-dose and within 10 minutes of end of infusion on Days 1, 85 and 113; Pre-dose on Days 29, 57 and 169; and 90 days post last dose of MEDI4736. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively |
|
| Secondary |
Initial and Second Stage Cohorts: Serum Concentrations of Olaparib |
Blood samples were collected to determine the serum concentration of olaparib. |
Pre-dose and 0.5-1 hour postdose on Days 1 and 22 of monotherapy; Pre-dose and 0.5-1, 1-3, 3-6 and 6-12 hours postdose on Day 15 of combination therapy. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively |
|
| Secondary |
Second Stage Cohort: Serum Concentrations of Bevacizumab |
Blood samples were collected to determine the serum concentration of bevacizumab. |
Pre-dose and within 10 minutes of end of infusion on Days 1 and 85; Pre-dose on Days 29 and 169; and 90 days post last dose of bevacizumab. Assessed until DCO 17 Sep 2021 |
|
| Secondary |
Initial and Second Stage Cohorts: Number of Participants With Anti-Drug Antibody (ADA) Response to MEDI4736 |
Blood samples were measured for the presence of ADAs and ADA-neutralizing antibodies (nAb) for MEDI4736 using validated assays. ADA prevalence was defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. ADA incidence (treatment-emergent ADA) was defined as the sum of both treatment-induced (post-baseline ADA positive only) and treatment-boosted ADA. Treatment-boosted ADA was defined as baseline ADA titer that was boosted to 4-fold or higher following drug administration. Persistently positive was defined as positive at >=2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. |
Pre-dose on Days 1, 15, 57, 85, 113 and 169; and 90 days post-last dose of MEDI4736. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively |
|
