Metastatic Triple Negative Breast Cancer
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Brief summary
In this study, participants with metastatic triple negative breast cancer (mTNBC) will be randomly assigned to receive either single agent pembrolizumab or single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines, consisting of either capecitabine, eribulin, gemcitabine, or vinorelbine. The primary study hypothesis is that pembrolizumab extends overall survival compared to TPC.
Interventions
BIOLOGICALpembrolizumab
DRUGcapecitabine
DRUGeribulin
DRUGgemcitabine
DRUGvinorelbine
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Centrally confirmed Stage IV/M1 mTNBC * Newly obtained tumor biopsy from metastatic site * Central determination of programmed cell death ligand 1 (PD-L1) tumor status * Received either one or two prior systemic treatments for metastatic breast cancer and have documented disease progression on or after the most recent therapy * Previously treated with an anthracycline and/or taxane in the neoadjuvant/adjuvant or metastatic setting * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start * Adequate organ function
Exclusion criteria
* Participation in another clinical trial within 4 weeks * Monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks * Chemotherapy, targeted small molecule therapy, or radiation therapy within at least 2 weeks * Active autoimmune disease that required systemic treatment in the past 2 years * Diagnosed with immunodeficiency or receiving systemic steroid therapy or another form of immunosuppressive therapy within 7 days * Known additional malignancy that required treatment or progressed in last 5 years * Known active brain metastases and/or carcinomatous meningitis * Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand-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 protein 4 \[CTLA-4\], OX-40, CD137) or previously participated in any pembrolizumab (MK-3475) clinical studies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival in Participants With Programmed Cell Death Ligand 1 (PD-L1) With Combined Positive Score (CPS) ≥10 | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | Overall survival (OS) was defined as the time from randomization to death due to any cause. |
| Overall Survival in Participants With PD-L1 CPS ≥1 | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | Overall survival (OS) was defined as the time from randomization to death due to any cause. |
| Overall Survival in All Participants | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | Overall survival (OS) was defined as the time from randomization to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | Progression-Free Survival (PFS), based on BICR assessment per RECIST 1.1, was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. |
| Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | Progression-Free Survival (PFS), based on BICR assessment per RECIST 1.1, was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. |
| Progression-Free Survival Per RECIST 1.1 in All Participants | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | Progression-Free Survival (PFS), based on BICR assessment per RECIST 1.1, was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. |
| Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 Who Had a Confirmed Response | Up to approximately 36 months (from time of first documented evidence of CR or PR through Final Analysis database cutoff date of 11-April-2019) | For participants with PD-L1 CPS ≥10 who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, Duration of Response (DOR) was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR. |
| Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 Who Had a Confirmed Response | Up to approximately 36 months (from time of first documented evidence of CR or PR through Final Analysis database cutoff date of 11-April-2019) | For participants with PD-L1 CPS ≥1 who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, Duration of Response (DOR) was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR. |
| Overall Response Rate Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With PD-L1 CPS ≥10 | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | Overall Response Rate (ORR), based on a Blinded Independent Central Review (BICR) assessment per RECIST 1.1, was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions). |
| Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | Disease Control Rate (DCR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease for at least 24 weeks (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.\]) |
| Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | Disease Control Rate (DCR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease for at least 24 weeks (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.\]) |
| Disease Control Rate Per RECIST 1.1 in All Participants | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | Disease Control Rate (DCR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease for at least 24 weeks (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.\]) |
| Number of Participants Who Experienced One or More Adverse Events | Up to approximately 60 months | An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. |
| Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | Up to approximately 60 months | An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. |
| Duration of Response Per RECIST 1.1 in All Participants Who Had a Confirmed Response | Up to approximately 36 months (from time of first documented evidence of CR or PR through Final Analysis database cutoff date of 11-April-2019) | For participants who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, Duration of Response (DOR) was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR. |
| Overall Response Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | Overall Response Rate (ORR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions). |
| Overall Response Rate Per RECIST 1.1 in All Participants | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | Overall Response Rate (ORR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions). |
Participant flow
Pre-assignment details
Per protocol, response/progression or adverse events during the second pembrolizumab course were not counted towards efficacy outcome measures or safety outcome measures respectively.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab Participants received pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations (up to \
2 years). Qualified participants who received first course of pembrolizumab but continued to experience disease progression may have, at investigator's discretion, initiated a second course of pembrolizumab at 200 mg IV Q3W for up to 17 administrations (up to \
1 year). | 312 |
| Chemotherapy Participants received capecitabine, eribulin, gemcitabine, or vinorelbine as single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines. | 310 |
| Total | 622 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 274 | 262 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Sponsor Decision | 27 | 15 |
| Overall Study | Withdrawal by Subject | 11 | 32 |
Baseline characteristics
| Characteristic | Chemotherapy | Total | Pembrolizumab |
|---|---|---|---|
| Age, Continuous | 52.6 Years STANDARD_DEVIATION 11.2 | 52.0 Years STANDARD_DEVIATION 11.3 | 51.4 Years STANDARD_DEVIATION 11.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 101 Participants | 188 Participants | 87 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 17 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 12 Participants | 24 Participants | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 22 Participants | 13 Participants |
| Race (NIH/OMB) White | 180 Participants | 363 Participants | 183 Participants |
| Sex: Female, Male Female | 308 Participants | 620 Participants | 312 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 283 / 312 | 289 / 310 | 0 / 8 |
| other Total, other adverse events | 259 / 309 | 263 / 292 | 4 / 8 |
| serious Total, serious adverse events | 65 / 309 | 60 / 292 | 1 / 8 |
Outcome results
Primary
Overall Survival in All Participants
Overall survival (OS) was defined as the time from randomization to death due to any cause.
Time frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Population: All participants who were included in a treatment group at randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Overall Survival in All Participants | 9.9 Months |
| Chemotherapy | Overall Survival in All Participants | 10.8 Months |
p-value: 0.380295% CI: [0.82, 1.15]Regression, Cox
Primary
Overall Survival in Participants With PD-L1 CPS ≥1
Overall survival (OS) was defined as the time from randomization to death due to any cause.
Time frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Population: All participants with PD-L1 CPS ≥1 who were included in a treatment group at randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Overall Survival in Participants With PD-L1 CPS ≥1 | 10.7 Months |
| Chemotherapy | Overall Survival in Participants With PD-L1 CPS ≥1 | 10.2 Months |
p-value: 0.072895% CI: [0.69, 1.06]Regression, Cox
Primary
Overall Survival in Participants With Programmed Cell Death Ligand 1 (PD-L1) With Combined Positive Score (CPS) ≥10
Overall survival (OS) was defined as the time from randomization to death due to any cause.
Time frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Population: All participants with PD-L1 CPS ≥10 who were included in a treatment group at randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Overall Survival in Participants With Programmed Cell Death Ligand 1 (PD-L1) With Combined Positive Score (CPS) ≥10 | 12.7 Months |
| Chemotherapy | Overall Survival in Participants With Programmed Cell Death Ligand 1 (PD-L1) With Combined Positive Score (CPS) ≥10 | 11.6 Months |
p-value: 0.057495% CI: [0.57, 1.06]Regression, Cox
Secondary
Disease Control Rate Per RECIST 1.1 in All Participants
Disease Control Rate (DCR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease for at least 24 weeks (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.\])
Time frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Population: All participants who were included in a treatment group at randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Disease Control Rate Per RECIST 1.1 in All Participants | 12.2 Percentage of participants |
| Chemotherapy | Disease Control Rate Per RECIST 1.1 in All Participants | 18.7 Percentage of participants |
p-value: 0.987795% CI: [-12.2, -0.8]Miettinen & Nurminen method
Secondary
Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1
Disease Control Rate (DCR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease for at least 24 weeks (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.\])
Time frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Population: All participants with PD-L1 CPS ≥1 who were included in a treatment group at randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 | 14.3 Percentage of participants |
| Chemotherapy | Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 | 15.8 Percentage of participants |
p-value: 0.670195% CI: [-8.6, 5.5]Miettinen & Nurminen method
Secondary
Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥10
Disease Control Rate (DCR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease for at least 24 weeks (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.\])
Time frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Population: All participants with PD-L1 CPS ≥10 who were included in a treatment group at randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 | 19.8 Percentage of participants |
| Chemotherapy | Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 | 17.3 Percentage of participants |
p-value: 0.338895% CI: [-8.7, 13.5]Miettinen & Nurminen method
Secondary
Duration of Response Per RECIST 1.1 in All Participants Who Had a Confirmed Response
For participants who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, Duration of Response (DOR) was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR.
Time frame: Up to approximately 36 months (from time of first documented evidence of CR or PR through Final Analysis database cutoff date of 11-April-2019)
Population: All randomized participants, regardless of whether or not they received study treatment, who demonstrated a confirmed response (CR or PR). Participants were included in the treatment arm to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Duration of Response Per RECIST 1.1 in All Participants Who Had a Confirmed Response | 12.2 Months |
| Chemotherapy | Duration of Response Per RECIST 1.1 in All Participants Who Had a Confirmed Response | NA Months |
Secondary
Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 Who Had a Confirmed Response
For participants with PD-L1 CPS ≥10 who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, Duration of Response (DOR) was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR.
Time frame: Up to approximately 36 months (from time of first documented evidence of CR or PR through Final Analysis database cutoff date of 11-April-2019)
Population: All randomized participants with PD-L1 CPS ≥10, whether or not they received study treatment, who demonstrated a confirmed response (CR or PR). Participants were included in the treatment arm to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 Who Had a Confirmed Response | NA Months |
| Chemotherapy | Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 Who Had a Confirmed Response | 7.1 Months |
Secondary
Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 Who Had a Confirmed Response
For participants with PD-L1 CPS ≥1 who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, Duration of Response (DOR) was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR.
Time frame: Up to approximately 36 months (from time of first documented evidence of CR or PR through Final Analysis database cutoff date of 11-April-2019)
Population: All randomized participants with PD-L1 CPS ≥1, regardless of whether or not they received study treatment, who demonstrated a confirmed response (CR or PR). Participants were included in the treatment arm to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 Who Had a Confirmed Response | 12.2 Months |
| Chemotherapy | Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 Who Had a Confirmed Response | NA Months |
Secondary
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time frame: Up to approximately 60 months
Population: All randomized participants who received at least 1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | 14 Participants |
| Chemotherapy | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | 16 Participants |
Secondary
Number of Participants Who Experienced One or More Adverse Events
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time frame: Up to approximately 60 months
Population: All randomized participants who received at least 1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Number of Participants Who Experienced One or More Adverse Events | 285 Participants |
| Chemotherapy | Number of Participants Who Experienced One or More Adverse Events | 281 Participants |
Secondary
Overall Response Rate Per RECIST 1.1 in All Participants
Overall Response Rate (ORR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions).
Time frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Population: All participants who were included in a treatment group at randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Overall Response Rate Per RECIST 1.1 in All Participants | 9.6 Percentage of participants |
| Chemotherapy | Overall Response Rate Per RECIST 1.1 in All Participants | 10.6 Percentage of participants |
p-value: 0.662995% CI: [-5.9, 3.8]Miettinen & Nurminen method
Secondary
Overall Response Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1
Overall Response Rate (ORR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions).
Time frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Population: All participants with PD-L1 CPS ≥1 who were included in a treatment group at randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Overall Response Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 | 12.3 Percentage of participants |
| Chemotherapy | Overall Response Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 | 9.4 Percentage of participants |
p-value: 0.175295% CI: [-3.3, 9.2]Miettinen & Nurminen method
Secondary
Overall Response Rate Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With PD-L1 CPS ≥10
Overall Response Rate (ORR), based on a Blinded Independent Central Review (BICR) assessment per RECIST 1.1, was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions).
Time frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Population: All participants with PD-L1 CPS ≥10 who were included in a treatment group at randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Overall Response Rate Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With PD-L1 CPS ≥10 | 17.7 Percentage of participants |
| Chemotherapy | Overall Response Rate Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With PD-L1 CPS ≥10 | 9.2 Percentage of participants |
p-value: 0.045795% CI: [-1.4, 18.4]Miettinen & Nurminen method
Secondary
Progression-Free Survival Per RECIST 1.1 in All Participants
Progression-Free Survival (PFS), based on BICR assessment per RECIST 1.1, was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Time frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Population: All participants who were included in a treatment group at randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Progression-Free Survival Per RECIST 1.1 in All Participants | 2.1 Months |
| Chemotherapy | Progression-Free Survival Per RECIST 1.1 in All Participants | 3.3 Months |
p-value: 195% CI: [1.33, 1.92]Regression, Cox
Secondary
Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥1
Progression-Free Survival (PFS), based on BICR assessment per RECIST 1.1, was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Time frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Population: All participants with PD-L1 CPS ≥1 who were included in a treatment group at randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 | 2.1 Months |
| Chemotherapy | Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 | 3.1 Months |
p-value: 0.996495% CI: [1.08, 1.68]Regression, Cox
Secondary
Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥10
Progression-Free Survival (PFS), based on BICR assessment per RECIST 1.1, was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Time frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Population: All participants with PD-L1 CPS ≥10 who were included in a treatment group at randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 | 2.1 Months |
| Chemotherapy | Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 | 3.4 Months |
p-value: 0.793695% CI: [0.82, 1.59]Regression, Cox