Urothelial Cancer
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2), bladder cancer
Brief summary
This is a study using pembrolizumab (MK-3475, KEYTRUDA®) for first-line treatment of participants with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy. The primary study objective is to determine the objective response rate (ORR) in all participants and by programmed cell death ligand 1 (PD-L1) status. With Amendment 4, once a participant has achieved the study objective or the study has ended, the participant will be discontinued from this study and will be enrolled in an extension study to continue protocol-defined assessments and treatment.
Detailed description
Participants receiving pembrolizumab who attain a complete response (CR) may consider stopping trial treatment if they meet criteria for holding therapy. Participants who stop trial treatment after receiving 24 months of trial treatment for reasons other than progressive disease (PD) or intolerability, or participants who attain a CR and stop trial treatment may be eligible for up to one year of retreatment upon experiencing PD.
Interventions
BIOLOGICALpembrolizumab
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra (transitional cell and mixed transitional/non-transitional cell histologies) * Ineligible for cisplatin therapy * No prior systemic chemotherapy for metastatic disease (adjuvant or neoadjuvant platinum-based chemotherapy with recurrence \>12 months since completion of therapy is allowed) * Available tissue from a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated * Measurable disease * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 * Adequate organ function * Female participants of childbearing potential have a negative urine or serum pregnancy test; surgically sterile, or willing to use 2 acceptable methods of birth control, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment * Male participants must be willing to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study treatment
Exclusion criteria
* Disease that is suitable for local therapy administered with curative intent * Currently participating or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study treatment * Prior anti-cancer monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier * Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from AEs due to a previously administered agent * Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cancer * Known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Active autoimmune disease that has required systemic treatment in past 2 years * Evidence of interstitial lung disease or active non-infectious pneumonitis * Active infection requiring systemic therapy * Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of study treatment * Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor * Known human immunodeficiency virus (HIV) * Known active Hepatitis B or C * Received a live virus vaccine within 30 days of planned start of study treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | Up to approximately 80.5 months | ORR was determined in all participants and 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) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | Up to approximately 80.5 months | ORR was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. ORR 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) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | Up to approximately 80.5 months | ORR was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. ORR 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) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | Up to approximately 80.5 months | DOR was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, and had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death and was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | Up to approximately 80.5 months | PFS was determined in all participants. PFS 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 as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | Up to approximately 80.5 months | PFS was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. PFS 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 as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | Up to approximately 80.5 months | PFS was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. PFS 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 as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Overall Survival (OS) in All Participants | Up to approximately 80.5 months | OS was determined for all participants and was defined as the time from randomization to death due to any cause. OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | Up to approximately 80.5 months | OS was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay. OS was defined as the time from randomization to death due to any cause. OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | Up to approximately 80.5 months | OS was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. OS was defined as the time from randomization to death due to any cause. OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Progression Free Survival Rate (PFS Rate) at Month 6 in All Participants | Month 6 | The PFS rate was determined in all participants at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | Month 6 | The PFS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | Month 6 | The PFS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | Month 12 | The PFS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | Month 12 | The PFS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Overall Survival Rate (OS Rate) at Month 6 in All Participants | Month 6 | The OS rate was determined for all participants at Month 6 and was defined as the time from randomization to death due to any cause. OS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | Month 6 | The OS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 6. OS was defined as the time from randomization to death due to any cause. OS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | Month 6 | The OS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 6. OS was defined as the time from randomization to death due to any cause. OS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Overall Survival Rate (OS Rate) at Month 12 in All Participants | Month 12 | The OS rate was determined for all participants at Month 12 and was defined as the time from randomization to death due to any cause. OS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | Month 12 | The OS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 12. OS was defined as the time from randomization to death due to any cause. OS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | Month 12 | The OS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 12. OS was defined as the time from randomization to death due to any cause. OS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Programmed Cell Death Ligand 1 (PD-L1) Expression Status | Day 1 | PD-L1 expression status was determined as the percent of disease tumor cells, from newly obtained tumor biopsies, demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. The assay uses a Combined Positive Score (CPS) as a measure of PD-L1 positivity. The CPS is calculated as the number of PD-L1-positive cells divided by the number of viable tumor cells analyzed multiplied by 100. A CPS of \<1% = negative; ≥1% = positive; and ≥10% = strongly positive. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Number of Participants Who Experienced At Least One Adverse Event (AE) | Up to approximately 80.5 months | An AE was defined as any untoward medical occurrence in a participant administered a study treatment and did not necessarily 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. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | Up to approximately 26 months | An AE was defined as any untoward medical occurrence in a participant administered a study treatment and did not necessarily 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. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Progression Free Survival Rate (PFS Rate) at Month 12 in All Participants | Month 12 | The PFS rate was determined in all participants at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | Up to approximately 80.5 months | DOR was determined in participants who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death and was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | Up to approximately 80.5 months | DOR was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, and had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death and was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in All Participants | Up to approximately 80.5 months | ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | Up to approximately 80.5 months | ORR was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
| Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | Up to approximately 80.5 months | ORR was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis. |
Participant flow
Recruitment details
Participants were eligible to receive second course treatment with pembrolizumab if they met criteria for re-treatment. Per protocol, only data generated during the initial course of treatment contributed to efficacy and safety outcome measures.
Pre-assignment details
Results are based on a database cutoff date of 18-February-2022.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab 200 mg Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year. | 374 |
| Total | 374 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 25 |
| Overall Study | Death | 273 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Participation in study terminated by Sponsor | 39 |
| Overall Study | Physician Decision | 13 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Screen failure | 1 |
| Overall Study | Withdrawal by Subject | 19 |
Baseline characteristics
| Characteristic | Pembrolizumab 200 mg |
|---|---|
| Age, Continuous | 73.0 Years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 326 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 26 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 332 Participants |
| Sex: Female, Male Female | 86 Participants |
| Sex: Female, Male Male | 288 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 305 / 374 | 8 / 13 |
| other Total, other adverse events | 342 / 370 | 12 / 13 |
| serious Total, serious adverse events | 190 / 370 | 6 / 13 |
Outcome results
Primary
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
ORR was determined in all participants and 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) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment during the initial course of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | 28.9 Percentage of participants |
Primary
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
ORR was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. ORR 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) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | 32.6 Percentage of participants |
Primary
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
ORR was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. ORR 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) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 strong positive expression of ≥10% CPS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | 47.3 Percentage of participants |
Secondary
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
DOR was determined in participants who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death and was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and who had a confirmed CR or confirmed PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg | Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | 33.4 Months |
Secondary
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
DOR was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, and had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death and was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment during the initial course of treatment, had a PD-L1 positive expression of ≥1% CPS, and who had a confirmed CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg | Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | 35.8 Months |
Secondary
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
DOR was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, and had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death and was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment during the initial course of treatment, had a PD-L1 strong positive expression of ≥10% CPS, and who had a confirmed CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg | Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | NA Months |
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 did not necessarily 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. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 26 months
Population: All participants who received at least one dose of study treatment during the initial course of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab 200 mg | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 62 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 did not necessarily 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. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment during the initial course of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab 200 mg | Number of Participants Who Experienced At Least One Adverse Event (AE) | 361 Participants |
Secondary
Overall Survival (OS) in All Participants
OS was determined for all participants and was defined as the time from randomization to death due to any cause. OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment during the initial course of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg | Overall Survival (OS) in All Participants | 11.3 Months |
Secondary
Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
OS was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay. OS was defined as the time from randomization to death due to any cause. OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg | Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | 12.4 Months |
Secondary
Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
OS was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. OS was defined as the time from randomization to death due to any cause. OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 strong positive expression of ≥10% CPS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg | Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | 18.5 Months |
Secondary
Overall Survival Rate (OS Rate) at Month 12 in All Participants
The OS rate was determined for all participants at Month 12 and was defined as the time from randomization to death due to any cause. OS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Month 12
Population: All participants who received at least one dose of study treatment during the initial course of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Overall Survival Rate (OS Rate) at Month 12 in All Participants | 46.9 Percentage of participants |
Secondary
Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
The OS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 12. OS was defined as the time from randomization to death due to any cause. OS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Month 12
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | 50.9 Percentage of participants |
Secondary
Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
The OS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 12. OS was defined as the time from randomization to death due to any cause. OS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Month 12
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 strong positive expression of ≥10% CPS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | 60.7 Percentage of participants |
Secondary
Overall Survival Rate (OS Rate) at Month 6 in All Participants
The OS rate was determined for all participants at Month 6 and was defined as the time from randomization to death due to any cause. OS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Month 6
Population: All participants who received at least one dose of study treatment during the initial course of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Overall Survival Rate (OS Rate) at Month 6 in All Participants | 67.0 Percentage of participants |
Secondary
Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
The OS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 6. OS was defined as the time from randomization to death due to any cause. OS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Month 6
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | 71.3 Percentage of participants |
Secondary
Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
The OS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 6. OS was defined as the time from randomization to death due to any cause. OS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Month 6
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 strong positive expression of ≥10% CPS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | 76.3 Percentage of participants |
Secondary
Programmed Cell Death Ligand 1 (PD-L1) Expression Status
PD-L1 expression status was determined as the percent of disease tumor cells, from newly obtained tumor biopsies, demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. The assay uses a Combined Positive Score (CPS) as a measure of PD-L1 positivity. The CPS is calculated as the number of PD-L1-positive cells divided by the number of viable tumor cells analyzed multiplied by 100. A CPS of \<1% = negative; ≥1% = positive; and ≥10% = strongly positive. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Day 1
Population: All participants who received at least one dose of study treatment during the initial course of treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pembrolizumab 200 mg | Programmed Cell Death Ligand 1 (PD-L1) Expression Status | PD-L1 CPS <1% | 79 Participants |
| Pembrolizumab 200 mg | Programmed Cell Death Ligand 1 (PD-L1) Expression Status | PD-L1 CPS ≥1% to <10% | 172 Participants |
| Pembrolizumab 200 mg | Programmed Cell Death Ligand 1 (PD-L1) Expression Status | PD-L1 CPS ≥10% | 110 Participants |
| Pembrolizumab 200 mg | Programmed Cell Death Ligand 1 (PD-L1) Expression Status | Unknown | 9 Participants |
Secondary
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
PFS was determined in all participants. PFS 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 as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment during the initial course of treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg | Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants | 2.5 Months |
Secondary
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
PFS was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. PFS 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 as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg | Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | 3.4 Months |
Secondary
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
PFS was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. PFS 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 as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 strong positive expression of ≥10% CPS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg | Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | 4.9 Months |
Secondary
Progression Free Survival Rate (PFS Rate) at Month 12 in All Participants
The PFS rate was determined in all participants at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Month 12
Population: All participants who received at least one dose of study treatment during the initial course of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Progression Free Survival Rate (PFS Rate) at Month 12 in All Participants | 22.9 Percentage of participants |
Secondary
Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
The PFS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Month 12
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | 25.8 Percentage of participants |
Secondary
Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
The PFS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Month 12
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 strong positive expression of ≥10% CPS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | 38.6 Percentage of participants |
Secondary
Progression Free Survival Rate (PFS Rate) at Month 6 in All Participants
The PFS rate was determined in all participants at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Month 6
Population: All participants who received at least one dose of study treatment during the initial course of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Progression Free Survival Rate (PFS Rate) at Month 6 in All Participants | 34.0 Percentage of participants |
Secondary
Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
The PFS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Month 6
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | 37.9 Percentage of participants |
Secondary
Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
The PFS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Month 6
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 strong positive expression of ≥10% CPS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | 49.0 Percentage of participants |
Other Pre-specified
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in All Participants
ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment during the initial course of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in All Participants | 30.5 Percentage of participants |
Other Pre-specified
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
ORR was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥1% CPS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | 34.4 Percentage of participants |
Other Pre-specified
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
ORR was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Time frame: Up to approximately 80.5 months
Population: All participants who received at least one dose of study treatment, during the initial course of treatment, and had a PD-L1 positive expression of ≥10% CPS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | 49.1 Percentage of participants |