Non-small Cell Lung Cancer
Conditions
Keywords
PD-1, PD1, PD-L1, PDL1
Brief summary
In this study, participants with programmed cell death ligand 1 (PD-L1)-positive non-small cell lung cancer (NSCLC) will be randomized to receive single agent pembrolizumab for up to 35 treatments or standard of care (SOC) platinum-based chemotherapy (carboplatin + paclitaxel or carboplatin + pemetrexed for 4 to 6 21-day cycles). Participants in the platinum-based chemotherapy arms with non-squamous tumor histologies may receive pemetrexed maintenance therapy after the 4 to 6 cycles of chemotherapy. The primary study hypothesis is that pembrolizumab prolongs overall survival (OS) compared to SOC chemotherapy.
Detailed description
Pembrolizumab-treated participants, who attain a confirmed complete response (CR) or who stop trial treatment after 35 administrations of study medication for reasons other than disease progression or intolerability, may consider stopping trial treatment. These participants may be eligible for re-treatment with pembrolizumab monotherapy after they have experienced radiographic disease according to protocol-defined criteria. Response or progression in the Second Course Phase will not count towards the objective response rate (ORR) and progression free survival (PFS) endpoints in this trial. The global study for MK-3475-042 enrolled 1274 participants. Of the 1274 total participants enrolled in the global study, 92 were also enrolled in the China extension study for MK-3475-042 (NCT03850444).
Interventions
BIOLOGICALpembrolizumab
DRUGcarboplatin
DRUGpaclitaxel
DRUGpemetrexed
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
* Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSCLC * PD-L1 positive tumor * Measureable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 * Life expectancy of at least 3 months * No prior systemic chemotherapy for the treatment of the participant's advanced or metastatic disease (treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior to diagnosis of advanced or metastatic disease) * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Adequate organ function * No prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy * Submission of formalin-fixed diagnostic tumor tissue (in the case of participants having received adjuvant systemic therapy, the tissue should be taken after completion of this therapy) * Female participants of childbearing potential must have a negative urine or serum pregnancy test and must be willing to use two adequate barrier methods of contraception or a barrier method plus a hormonal method starting with the screening visit through 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapeutic agents used in the study * Male participants with a female partner(s) of child-bearing potential must be willing to use two adequate barrier methods of contraception from screening through 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapeutic agents used in the study
Exclusion criteria
* Epidermal growth factor receptor (EGFR)-sensitizing mutation and/or is echinoderm microtubule-associated protein-like 4(EML4) gene/anaplastic lymphoma kinase (ALK) gene fusion positive * Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study therapy * No tumor specimen evaluable for PD-L1 expression by the central study laboratory * Squamous histology and received carboplatin in combination with paclitaxel in the adjuvant setting * Is receiving systemic steroid therapy ≤3 days prior to the first dose of study therapy or receiving any other form of immunosuppressive medication with the exception of daily steroid replacement therapy * The NSCLC can be treated with curative intent with either surgical resection and/or chemoradiation * Expected to require any other form of systemic or localized antineoplastic therapy while on study * Any prior systemic cytotoxic chemotherapy, biological therapy or major surgery within 3 weeks of the first dose of study therapy; received lung radiation therapy \>30 Gy within 6 months of the first dose of study therapy * Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) * Known central nervous system metastases and/or carcinomatous meningitis * Active autoimmune disease that has required systemic treatment in the past 2 years * Had allogeneic tissue/solid organ transplantation * Interstitial lung disease or history of pneumonitis that has required oral or IV steroids * Has received or will receive a live vaccine within 30 days prior to the first study therapy (seasonal flu vaccines that do not contain live vaccine are permitted) * Active infection requiring intravenous systemic therapy * Known history of human immunodeficiency virus (HIV) * Known active Hepatitis B or C * Regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol) * Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50% | Up to approximately 44 months | OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥50% is presented. |
| Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20% | Up to approximately 44 months | OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥20% is presented. |
| Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1% | Up to approximately 44 months | OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥1% is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50% | Up to approximately 44 months | PFS was determined for participants with a TPS of ≥50% and 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, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥50% is presented. |
| Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20% | Up to approximately 44 months | PFS was determined for participants with a TPS of ≥20% and 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, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥20% is presented. |
| Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1% | Up to approximately 44 months | PFS was determined for participants with a TPS of ≥1% and 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, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥1% is presented. |
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50% | Up to approximately 44 months | ORR was determined for participants with a TPS of ≥50%. ORR was determined per RECIST 1.1 and 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 of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥50% and who experienced a CR or PR is presented. |
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20% | Up to approximately 44 months | ORR was determined for participants with a TPS of ≥20%. ORR was determined per RECIST 1.1 and 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 of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥20% and who experienced a CR or PR is presented. |
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1% | Up to approximately 44 months | ORR was determined for participants with a TPS of ≥1%. ORR was determined per RECIST 1.1 and 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 of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥1% and who experienced a CR or PR is presented. |
| Number of Participants Who Experienced At Least One Adverse Event (AE) | Up to approximately 38 months | An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE 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 study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented. |
| Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | Up to approximately 35 months | An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which did 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 study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented. |
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Recruitment details
Of the 1275 participants randomized (pembrolizumab=638, chemotherapy=637), 1 participant assigned to receive pembrolizumab died prior to randomization and was randomized in error. The intent to treat population was defined as participants alive at the time of randomization, so the actual randomized population included 637 participants in each arm.
Pre-assignment details
Pembrolizumab-treated participants, who attained a confirmed complete response (CR) or who stopped trial treatment after 35 administrations of study medication for reasons other than disease progression or intolerability, could consider stopping trial treatment. These participants may have been eligible for re-treatment with pembrolizumab monotherapy after they had experienced radiographic disease as per protocol-defined criteria.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles) | 637 |
| Chemotherapy (SOC Treatment) Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m\^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m\^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m\^2 by IV infusion on Day 1 Q3W | 637 |
| Total | 1,274 |
Baseline characteristics
| Characteristic | Pembrolizumab | Total | Chemotherapy (SOC Treatment) |
|---|---|---|---|
| Age, Continuous | 62.5 Years STANDARD_DEVIATION 9.9 | 62.8 Years STANDARD_DEVIATION 9.7 | 63.1 Years STANDARD_DEVIATION 9.4 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS=0 | 197 Participants | 389 Participants | 192 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS=1 | 439 Participants | 884 Participants | 445 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS=2 | 1 Participants | 1 Participants | 0 Participants |
| Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status TPS=<1% | 0 Participants | 0 Participants | 0 Participants |
| Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status TPS=1-19% | 224 Participants | 456 Participants | 232 Participants |
| Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status TPS=20-49% | 114 Participants | 219 Participants | 105 Participants |
| Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status TPS=≥50% | 299 Participants | 599 Participants | 300 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 10 Participants | 15 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 189 Participants | 376 Participants | 187 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 23 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 30 Participants | 49 Participants | 19 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 398 Participants | 810 Participants | 412 Participants |
| Sex: Female, Male Female | 187 Participants | 372 Participants | 185 Participants |
| Sex: Female, Male Male | 450 Participants | 902 Participants | 452 Participants |
| Tumor Histology Non-squamous | 395 Participants | 783 Participants | 388 Participants |
| Tumor Histology Squamous | 242 Participants | 491 Participants | 249 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 528 / 637 | 582 / 637 | 18 / 34 |
| other Total, other adverse events | 535 / 636 | 577 / 615 | 21 / 34 |
| serious Total, serious adverse events | 261 / 636 | 193 / 615 | 8 / 34 |
Outcome results
Primary
Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1%
OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥1% is presented.
Time frame: Up to approximately 44 months
Population: The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥1%.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1% | 16.4 Months |
| Chemotherapy (SOC Treatment) | Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1% | 12.1 Months |
p-value: 0.001395% CI: [0.71, 0.93]Log Rank
Primary
Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20%
OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥20% is presented.
Time frame: Up to approximately 44 months
Population: The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥20%.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20% | 18.0 Months |
| Chemotherapy (SOC Treatment) | Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20% | 13.0 Months |
p-value: 0.001295% CI: [0.65, 0.91]Log Rank
Primary
Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50%
OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥50% is presented.
Time frame: Up to approximately 44 months
Population: The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥50%.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50% | 20.0 Months |
| Chemotherapy (SOC Treatment) | Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50% | 12.2 Months |
p-value: 0.000395% CI: [0.58, 0.86]Log Rank
Secondary
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which did 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 study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented.
Time frame: Up to approximately 35 months
Population: The analysis population consisted of all participants who received ≥1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 126 Participants |
| Chemotherapy (SOC Treatment) | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 93 Participants |
Secondary
Number of Participants Who Experienced At Least One Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE 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 study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented.
Time frame: Up to approximately 38 months
Population: The analysis population consisted of all participants who received ≥1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Number of Participants Who Experienced At Least One Adverse Event (AE) | 608 Participants |
| Chemotherapy (SOC Treatment) | Number of Participants Who Experienced At Least One Adverse Event (AE) | 606 Participants |
Secondary
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%
ORR was determined for participants with a TPS of ≥1%. ORR was determined per RECIST 1.1 and 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 of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥1% and who experienced a CR or PR is presented.
Time frame: Up to approximately 44 months
Population: The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥1%.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1% | 27.2 Percentage of participants |
| Chemotherapy (SOC Treatment) | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1% | 26.5 Percentage of participants |
p-value: 0.40695% CI: [-4.2, 5.4]Stratified Miettinen and Nurminen
Secondary
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%
ORR was determined for participants with a TPS of ≥20%. ORR was determined per RECIST 1.1 and 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 of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥20% and who experienced a CR or PR is presented.
Time frame: Up to approximately 44 months
Population: The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥20%.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20% | 33.2 Percentage of participants |
| Chemotherapy (SOC Treatment) | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20% | 28.9 Percentage of participants |
p-value: 0.074495% CI: [-1.7, 10.9]Stratified Miettinen and Nurminen
Secondary
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%
ORR was determined for participants with a TPS of ≥50%. ORR was determined per RECIST 1.1 and 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 of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥50% and who experienced a CR or PR is presented.
Time frame: Up to approximately 44 months
Population: The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥50%.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50% | 39.1 Percentage of participants |
| Chemotherapy (SOC Treatment) | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50% | 32.0 Percentage of participants |
p-value: 0.035395% CI: [-0.6, 14.6]Stratified Miettinen and Nurminen
Secondary
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%
PFS was determined for participants with a TPS of ≥1% and 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, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥1% is presented.
Time frame: Up to approximately 44 months
Population: The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥1%.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1% | 5.4 Months |
| Chemotherapy (SOC Treatment) | Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1% | 6.6 Months |
p-value: 0.796495% CI: [0.93, 1.19]Log Rank
Secondary
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%
PFS was determined for participants with a TPS of ≥20% and 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, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥20% is presented.
Time frame: Up to approximately 44 months
Population: The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥20%.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20% | 6.2 Months |
| Chemotherapy (SOC Treatment) | Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20% | 6.7 Months |
p-value: 0.213495% CI: [0.8, 1.1]Log Rank
Secondary
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%
PFS was determined for participants with a TPS of ≥50% and 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, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥50% is presented.
Time frame: Up to approximately 44 months
Population: The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥50%.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50% | 6.5 Months |
| Chemotherapy (SOC Treatment) | Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50% | 6.4 Months |
p-value: 0.02695% CI: [0.69, 1]Log Rank