Efficacy and Safety Study of Pembrolizumab (MK-3475) in Participants With Advanced Recurrent Ovarian Cancer (MK-3475-100/KEYNOTE-100)
- Conditions
- Ovarian Neoplasms
- Interventions
- Biological: Pembrolizumab
- Registration Number
- NCT02674061
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This study will assess the efficacy and safety of pembrolizumab (MK-3475) monotherapy in female participants with recurrent ovarian cancer (ROC) who have received up to 5 prior lines of treatment including platinum-based treatment for ROC (1 to 6 total prior lines counting front line therapy). Participants will be enrolled into two separate cohorts based on the number of prior lines of treatment received for ROC. There will be no hypothesis testing in this study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 376
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Has histologically confirmed epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer
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Has received a front line platinum-based regimen (administered via either intravenous or intraperitoneal route) per local standard of care or treatment guideline following the primary or interval debulking surgery with documented disease recurrence (note: Maintenance treatment following the front line treatment is permitted and counted together as part of the front line treatment)
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Has fulfilled the following additional requirements regarding prior treatments for ROC depending on the cohort participant is to be enrolled. Each participant must have documented evidence of clinical response or disease stabilization to the last regimen received.
- Cohort A: Has received 0 to 2 additional prior lines for treating ROC (or 1-3 total prior lines counting the front line) and must have a platinum-free interval (PFI) of ≥ 3 to 12 months if the last regimen received is a platinum-based, or a treatment-free interval (TFI) of ≥ 3 to 12 months if the last regimen received is a non-platinum-based
- Cohort B: Has received 3 to 5 additional prior lines for treating ROC (or 4-6 total prior lines counting the front line) and must have a PFI of ≥ 3 months if the last regimen received is a platinum-based, or a TFI of ≥ 3 months if the last regimen received is a non-platinum-based
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Has measurable disease at baseline based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the central imaging vendor
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Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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Has a life expectancy of ≥16 weeks
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Has provided a tumor tissue sample either collected from prior cytoreductive surgery or fresh newly obtained tumor tissue at screening
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Has adequate organ function
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Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug
- Is currently participating in or has participated in a clinical study and received an investigational agent or used an investigational device within 4 weeks prior to the first dose of study treatment
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the planned first dose of the study
- Has had prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to the planned first dose of the study
- Has not recovered from AEs to ≤ Grade 1 or prior treatment level due to a previously administered agent
- Has epithelial ovarian cancer (EOC) with mucinous histology subtype
- Has a known additional malignancy that progressed or required active treatment within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they have stable brain metastases
- Has known history of, or any evidence of active, non-infectious pneumonitis
- Has an active infection requiring systemic therapy
- Has symptoms of bowel obstruction in the past 3 months
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
- Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug
- Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated antigen-4 [CTLA-4], tumor necrosis factor receptors OX-40 or CD137) or has participated in prior pembrolizumab (MK-3475) studies
- Has a known history of Human Immunodeficiency Virus (HIV)
- Has known active Hepatitis B or Hepatitis C
- Has received a live vaccine within 30 days of the planned first dose of the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: Pembrolizumab Pembrolizumab Participants in Cohort A received 0-2 prior lines of treatment for recurrent ovarian cancer (ROC; 1-3 total prior lines including front-line treatment) and will be administered pembrolizumab at a dose of 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to \~2 years). Qualified participants who complete 35 administrations of pembrolizumab but progress after discontinuation can initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to \~1 additional year). Cohort B: Pembrolizumab Pembrolizumab Participants in Cohort B received 3-5 prior lines of treatment for ROC (4-6 total prior lines including front-line treatment) and will be administered pembrolizumab at a dose of 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to \~2 years). Qualified participants who complete 35 administrations of pembrolizumab but progress after discontinuation can initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to \~1 additional year)
- Primary Outcome Measures
Name Time Method ORR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With Programmed Cell Death Ligand -1 (PD-L1) Combined Positive Score (CPS) ≥10 Up to ~43 months (through database cut-off date of 18-September-2019) ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter. The percentage of participants who experienced CR or PR per RECIST 1.1 by BICR is reported here as the ORR for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by immunohistochemistry (IHC) as CPS ≥10.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in All Cohort A and Cohort B Participants Up to ~43 months (through database cut-off date of 18-September-2019) ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters \[SOD\] of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter. The percentage of participants who experienced CR or PR per RECIST 1.1 by BICR is reported for all participants in Cohort A and Cohort B.
ORR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Up to ~43 months (through database cut-off date of 18-September-2019) ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter. The percentage of participants who experienced CR or PR per RECIST 1.1 by BICR is reported here as the ORR for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by immunohistochemistry (IHC) as CPS ≥1.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by BICR in All Cohort A and Cohort B Participants Month 18 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by BICR is reported for all participants in Cohort A and Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by Investigator in All Cohort A and Cohort B Participants Month 18 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by investigator is reported for all participants in Cohort A and Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Month 6 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by investigator is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.
Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Month 6 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 6 per RECIST 1.1 by BICR was not planned or executed in Cohort B.
DCR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Up to ~43 months (through database cut-off date of 18-September-2019) DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD \[at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD\]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 based on BICR. The percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by BICR is reported as the DCR, analyzed by test of binomial parameter, for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.
Progression Free Survival (PFS) Per RECIST 1.1 by BICR in All Cohort A and Cohort B Participants Up to ~58.8 months (through database cut-off date of 18-March-2021) PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. PFS per RECIST 1.1 by BICR is reported for all participants in Cohort A and Cohort B.
Duration of Response (DOR) Per RECIST 1.1 by BICR in All Cohort A and Cohort B Participants Up to ~43 months (through database cut-off date of 18-September-2019) For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 based on BICR, DOR was defined as time from first documented CR or PR until progressive disease (PD) or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is a ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR analyzed by Kaplan-Meier (KM) method is reported for all participants in Cohort A and Cohort B who had a confirmed CR or PR per RECIST 1.1 by BICR.
DOR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Up to ~43 months (through database cut-off date of 18-September-2019) For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 based on BICR, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD was defined as ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR analyzed by KM method is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and had a confirmed CR or PR per RECIST 1.1 by BICR.
Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by BICR in All Cohort A and Cohort B Participants Month 6 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by BICR is reported for all participants in Cohort A and Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Month 18 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.
DOR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Up to ~43 months (through database cut-off date of 18-September-2019) For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 based on BICR, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD was defined as ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR analyzed by KM method is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and had confirmed CR or PR per RECIST 1.1 by BICR.
Disease Control Rate (DCR) Per RECIST 1.1 by BICR in All Cohort A and Cohort B Participants Up to ~43 months (through database cut-off date of 18-September-2019) DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or Stable Disease (SD: Neither sufficient shrinkage for PR nor sufficient increase for PD \[at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD\]) or Non-CR/Non-PD (NN: does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 based on BICR. The percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by BICR is reported as the DCR, analyzed by test of binomial parameter, for all participants in Cohort A and Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Month 18 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.
Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Month 12 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.
ORR Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Up to ~43 months (through database cut-off date of 18-September-2019) ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was analyzed by test of binomial parameter. The percentage of participants who experienced CR or PR per RECIST 1.1 by investigator is reported as the ORR for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.
DCR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Up to ~43 months (through database cut-off date of 18-September-2019) DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD \[at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD\]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 based on BICR. The percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by BICR is reported as the DCR, analyzed by test of binomial parameter, for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.
PFS Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Up to ~43 months (through database cut-off date of 18-September-2019) PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. PFS per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.
ORR Per RECIST 1.1 by Investigator in All Cohort A and Cohort B Participants Up to ~43 months (through database cut-off date of 18-September-2019) ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was analyzed by test of binomial parameter. The percentage of participants who experienced CR or PR per RECIST 1.1 by investigator is reported as the ORR for all participants in Cohort A and Cohort B.
ORR Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Up to ~43 months (through database cut-off date of 18-September-2019) ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was analyzed by test of binomial parameter. The percentage of participants who experienced CR or PR per RECIST 1.1 by investigator is reported as the ORR for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.
DCR Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Up to ~43 months (through database cut-off date of 18-September-2019) DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD \[at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD\]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 by investigator assessment. The percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by investigator is reported as the DCR, analyzed by test of binomial parameter, for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.
PFS Per RECIST 1.1 by Investigator in All Cohort A and Cohort B Participants Up to ~43 months (through database cut-off date of 18-September-2019) PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. PFS per RECIST 1.1 by investigator is reported for all participants in Cohort A and Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by BICR in All Cohort A and Cohort B Participants Month 12 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by BICR is reported for all participants in Cohort A and Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Month 6 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.
Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Month 12 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.
PFS Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Up to ~43 months (through database cut-off date of 18-September-2019) PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. PFS per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.
Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Month 6 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by BICR is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.
DOR Per RECIST 1.1 by Investigator in All Cohort A and Cohort B Participants Up to ~43 months (through database cut-off date of 18-September-2019) For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is a ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR analyzed by KM method is reported for all participants in Cohort A and Cohort B who had a confirmed CR or PR per RECIST 1.1 by investigator.
DOR Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Up to ~43 months (through database cut-off date of 18-September-2019) For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD was defined as ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR analyzed by KM method is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10 and had a confirmed CR or PR per RECIST 1.1 by investigator.
DCR Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Up to ~43 months (through database cut-off date of 18-September-2019) DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD \[at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD\]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 by investigator assessment. The percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by investigator is reported as the DCR, analyzed by test of binomial parameter, for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.
DOR Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Up to ~43 months (through database cut-off date of 18-September-2019) For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD was defined as ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. DOR analyzed by KM method is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1 and had confirmed CR or PR per RECIST 1.1 by investigator.
Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by Investigator in All Cohort A and Cohort B Participants Month 6 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by investigator is reported for all participants in Cohort A and Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by Investigator in All Cohort A and Cohort B Participants Month 12 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by investigator is reported for all participants in Cohort A and Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Month 18 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS Rate) at Month 18 per RECIST 1.1 by investigator is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.
PFS Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Up to ~43 months (through database cut-off date of 18-September-2019) PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. Per protocol PFS per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS per RECIST 1.1 by BICR was not planned or executed in Cohort B.
DCR Per RECIST 1.1 by Investigator in All Cohort A and Cohort B Participants Up to ~43 months (through database cut-off date of 18-September-2019) DCR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD \[at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD\]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 by investigator assessment. The percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by investigator is reported as the DCR, analyzed by test of binomial parameter, for all participants in Cohort A and Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Month 12 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by investigator is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.
ORR Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With Platinum-Free Interval (PFI)/Treatment-Free Interval (TFI) ≥3-6 Months Up to ~43 months (through database cut-off date of 18-September-2019) ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter. Per protocol the percentage of participants who experienced CR or PR per RECIST 1.1 by BICR is reported as the ORR for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI \>3-6 months subgroup analysis of ORR per RECIST 1.1 by BICR was not planned or executed in Cohort B.
ORR Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/ TFI >6-12 Months Up to ~43 months (through database cut-off date of 18-September-2019) ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter. Per protocol the percentage of participants who experienced CR or PR per RECIST 1.1 by BICR is reported as the ORR for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI \>6-12 months subgroup analysis of ORR per RECIST 1.1 by BICR was not planned or executed in Cohort B.
DOR Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Up to ~43 months (through database cut-off date of 18-September-2019) For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 based on BICR, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is a ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. Per protocol DOR analyzed by KM method is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months who had a CR or PR per RECIST 1.1 by BICR. Per protocol PFI/TFI ≥3-6 months subgroup analysis of DOR per RECIST 1.1 by BICR was not planned or executed in Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Month 12 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI \>6-12 months subgroup analysis of PFS rate at Month 12 per RECIST 1.1 by BICR was not planned or executed in Cohort B.
PFS Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Up to ~43 months (through database cut-off date of 18-September-2019) PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. PFS per RECIST 1.1 by investigator is reported here for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.
Per protocol PFS per RECIST 1.1 by investigator was analyzed in the subgroup of Cohort A and Cohort B participants with CPS ≥10.Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Month 12 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS Rate) at Month 12 per RECIST 1.1 by investigator is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.
DOR Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Up to ~43 months (through database cut-off date of 18-September-2019) For participants who demonstrated confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 based on BICR, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is a ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. Per protocol DOR analyzed by KM method is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months who had a CR or PR per RECIST 1.1 by BICR. Per protocol PFI/TFI \>6-12 months subgroup analysis of DOR per RECIST 1.1 by BICR was not planned or executed in Cohort B.
ORR Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/ TFI ≥3-6 Months Up to ~43 months (through database cut-off date of 18-September-2019) ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was analyzed by test of binomial parameter. Per protocol the percentage of participants who experienced CR or PR per RECIST 1.1 by investigator is reported as the ORR for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of ORR per RECIST 1.1 by investigator was not planned or executed in Cohort B.
DOR Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Up to ~43 months (through database cut-off date of 18-September-2019) For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. Per protocol DOR analyzed by KM method is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months who had a CR or PR per RECIST 1.1 by investigator. Per protocol PFI/TFI ≥3-6 months subgroup analysis of DOR per RECIST 1.1 by investigator was not planned or executed in Cohort B.
DOR Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Up to ~43 months (through database cut-off date of 18-September-2019) For participants who demonstrated confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by investigator assessment, DOR was defined as time from first documented CR or PR until PD or death, whichever occurs first. DOR for participants who didn't progress or die at time of analysis was censored at last tumor assessment. Per RECIST 1.1 PD is ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. Per protocol DOR analyzed by KM method is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months who had a CR or PR per RECIST 1.1 by investigator. Per protocol PFI/TFI \>6-12 months subgroup analysis of DOR per RECIST 1.1 by investigator was not planned or executed in Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Month 18 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 18 per RECIST 1.1 by investigator was not planned or executed in Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Month 18 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by investigator is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.
PFS Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Up to ~43 months (through database cut-off date of 18-September-2019) PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. PFS per RECIST 1.1 by investigator is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.
Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by Investigator in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Month 6 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. The percentage of participants with PFS (PFS Rate) at Month 6 per RECIST 1.1 by investigator is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.
DCR Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Up to ~43 months (through database cut-off date of 18-September-2019) DCR was defined as the percentage of participants in the analysis population who have a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD \[at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD\]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 based on BICR. Per protocol the percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by BICR is reported as the DCR, analyzed by test of binomial parameter, for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of DCR per RECIST 1.1 by BICR was not planned or executed in Cohort B.
DCR Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Up to ~43 months (through database cut-off date of 18-September-2019) DCR was defined as the percentage of participants in the analysis population who have a CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage to for PR nor sufficient increase for PD \[at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD\]) or NN (does not qualify for CR or PD) for ≥24 weeks per RECIST 1.1 based on BICR. Per protocol the percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by BICR is reported as the DCR, analyzed by test of binomial parameter, for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI \>6-12 months subgroup analysis of DCR per RECIST 1.1 by BICR was not planned or executed in Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Month 6 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI \>6-12 months subgroup analysis of PFS rate at Month 6 per RECIST 1.1 by BICR was not planned or executed in Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Month 12 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 12 per RECIST 1.1 by BICR was not planned or executed in Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Month 18 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 18 per RECIST 1.1 by BICR was not planned or conducted in Cohort B.
PFS Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Up to ~43 months (through database cut-off date of 18-September-2019) PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. Per protocol PFS per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI \>6-12 months subgroup analysis of PFS per RECIST 1.1 by investigator was not planned or executed in Cohort B.
Overall Survival (OS) in All Cohort A and Cohort B Participants Up to ~58.8 months (through database cut-off date of 18-March-2021) OS was defined as the time from the first dose of study drug to death due to any cause. OS analyzed by KM method is reported for all participants in Cohort A and Cohort B.
Percentage of Participants With OS (OS Rate) at Month 18 in All Cohort A and Cohort B Participants Month 18 OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 18 is reported for all participants in Cohort A and Cohort B.
OS in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Up to ~43 months (through database cut-off date of 18-September-2019) OS was defined as the time from the first dose of study drug to death due to any cause. OS analyzed by KM method is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.
Percentage of Participants With OS (OS Rate) at Month 18 in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Month 18 OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 18 is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.
PFS Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Up to ~43 months (through database cut-off date of 18-September-2019) PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. Per protocol PFS per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI \>6-12 months subgroup analysis of PFS per RECIST 1.1 by BICR was not planned or executed in Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by BICR in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Month 18 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by BICR is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI \>6-12 months subgroup analysis of PFS rate at Month 18 per RECIST 1.1 by BICR was not planned or executed in Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Month 12 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 12 per RECIST 1.1 by investigator was not planned or executed in Cohort B.
Percentage of Participants With OS (OS Rate) at Month 6 in All Cohort A and Cohort B Participants Month 6 OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 6 is reported for all participants in Cohort A and Cohort B.
Percentage of Participants With OS (OS Rate) at Month 6 in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Month 6 OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 6 is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.
Percentage of Participants With OS (OS Rate) at Month 18 in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Month 18 OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 18 is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.
Percentage of Participants With OS (OS Rate) at Month 12 in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Month 12 OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 12 is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.
Percentage of Participants With OS (OS Rate) at Month 6 in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Month 6 OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol the percentage of participants with OS (OS rate) at Month 6 is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of OS rate at Month 6 was not planned or executed in Cohort B.
ORR Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/ TFI >6-12 Months Up to ~43 months (through database cut-off date of 18-September-2019) ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on investigator assessment. ORR was analyzed by test of binomial parameter. Per protocol the percentage of participants who experienced CR or PR per RECIST 1.1 by investigator is reported as the ORR for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI \>6-12 months subgroup analysis of ORR per RECIST 1.1 by investigator was not planned or executed in Cohort B.
DCR Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Up to ~43 months (through database cut-off date of 18-September-2019) DCR was defined as the percentage of participants in the analysis population who have CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD \[at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD\]) or NN (doesn't qualify for CR or PD) for ≥24 weeks per RECIST 1.1 by investigator assessment. Per protocol percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by investigator is reported as DCR, analyzed by test of binomial parameter, for subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of DCR per RECIST 1.1 by investigator was not planned or executed in Cohort B.
DCR Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Up to ~43 months (through database cut-off date of 18-September-2019) DCR was defined as the percentage of participants in the analysis population who have CR (Disappearance of all target lesions) or PR (≥30% decrease in SOD of target lesions) or SD (Neither sufficient shrinkage for PR nor sufficient increase for PD \[at ≥20% increase in target lesion SOD and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD\]) or NN (doesn't qualify for CR or PD) for ≥24 weeks per RECIST 1.1 by investigator assessment. Per protocol percentage of participants who experienced CR, PR, SD or NN per RECIST 1.1 by investigator is reported as DCR, analyzed by test of binomial parameter, for subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI\>6-12 months subgroup analysis of DCR per RECIST 1.1 by investigator was not planned or executed in Cohort B.
PFS Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Up to ~43 months (through database cut-off date of 18-September-2019) PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. PFS was analyzed by KM method. Per protocol PFS per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS per RECIST 1.1 by investigator was not planned or executed in Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Month 6 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of PFS rate at Month 6 per RECIST 1.1 by investigator was not planned or executed in Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 12 Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Month 12 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 12 per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI \>6-12 months subgroup analysis of PFS rate at Month 12 per RECIST 1.1 by investigator was not planned or executed in Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 18 Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Month 18 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 18 per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI \>6-12 months subgroup analysis of PFS rate at Month 18 per RECIST 1.1 by investigator was not planned or executed in Cohort B.
OS in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Up to ~43 months (through database cut-off date of 18-September-2019) OS was defined as the time from the first dose of study drug to death due to any cause. OS analyzed by KM method is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.
Number of Participants Who Experienced an Adverse Event (AE) Up to ~58.8 months (through database cut-off date of 18-March-2021) An AE was defined as any untoward medical occurrence in a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE could 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 medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. As specified by the protocol, the number of participants who experienced at least one AE is reported here for all participants in Cohort A and Cohort B.
Percentage of Participants With PFS (PFS Rate) at Month 6 Per RECIST 1.1 by Investigator in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Month 6 PFS was defined as the time from first dose of study treatment to the first documented PD per RECIST 1.1 by investigator assessment, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and an absolute SOD increase of ≥5 mm. The appearance of ≥1 new lesion is also PD. Per protocol the percentage of participants with PFS (PFS rate) at Month 6 per RECIST 1.1 by investigator is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI \>6-12 months subgroup analysis of PFS rate at Month 6 per RECIST 1.1 by investigator was not planned or executed in Cohort B.
Percentage of Participants With OS (OS Rate) at Month 12 in All Cohort A and Cohort B Participants Month 12 OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 12 is reported for all participants in Cohort A and Cohort B.
Percentage of Participants With OS (OS Rate) at Month 24 in All Cohort A and Cohort B Participants Month 24 OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 24 is reported for all participants in Cohort A and Cohort B.
Percentage of Participants With OS (OS Rate) at Month 6 in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1 Month 6 OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 6 is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥1.
Percentage of Participants With OS (OS Rate) at Month 12 in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Month 12 OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol the percentage of participants with OS (OS rate) at Month 12 is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI \>6-12 months subgroup analysis of OS rate at Month 12 was not planned or executed in Cohort B.
Percentage of Participants With OS (OS Rate) at Month 12 in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10 Month 12 OS was defined as the time from the first dose of study drug to death due to any cause. The percentage of participants with OS (OS rate) at Month 12 is reported for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by IHC as CPS ≥10.
Percentage of Participants With OS (OS Rate) at Month 6 in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Month 6 OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol the percentage of participants with OS (OS rate) at Month 6 is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI \>6-12 months subgroup analysis of OS rate at Month 6 was not planned or executed in Cohort B.
Percentage of Participants With OS (OS Rate) at Month 18 in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Month 18 OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol the percentage of participants with OS (OS rate) at Month 18 is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI \>6-12 months subgroup analysis of OS rate at Month 18 was not planned or executed in Cohort B.
OS in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Up to ~43 months (through database cut-off date of 18-September-2019) OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol OS analyzed by KM method is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of OS was not planned or executed in Cohort B.
Percentage of Participants With OS (OS Rate) at Month 12 in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Month 12 OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol the percentage of participants with OS (OS rate) at Month 12 is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of OS rate at Month 12 was not planned or executed in Cohort B.
OS in Subgroup of Cohort A Participants With PFI/TFI >6-12 Months Up to ~43 months (through database cut-off date of 18-September-2019) OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol OS analyzed by KM method is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) \>6-12 months. Per protocol PFI/TFI \>6-12 months subgroup analysis of OS was not planned or executed in Cohort B.
Percentage of Participants With OS (OS Rate) at Month 18 in Subgroup of Cohort A Participants With PFI/TFI ≥3-6 Months Month 18 OS was defined as the time from the first dose of study drug to death due to any cause. Per protocol the percentage of participants with OS (OS rate) at Month 18 is reported for the subgroup of Cohort A participants with PFI/TFI (duration from end of treatment to disease recurrence) ≥3-6 months. Per protocol PFI/TFI ≥3-6 months subgroup analysis of OS rate at Month 18 was not planned or executed in Cohort B.
Number of Participants Who Discontinued Study Treatment Due to an AE Up to ~58.8 months (through database cut-off date of 18-March-2021) An AE was defined as any untoward medical occurrence in a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE could 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 medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. As specified by the protocol, the number of participants who discontinued study treatment due to an AE is reported here for all participants in Cohort A and Cohort B.