Trial Outcomes & Findings for Testing the Addition of the Immunotherapy Drug Pembrolizumab to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) in Stage III-IV or Recurrent Endometrial Cancer (NCT NCT03914612)

Last Updated: 2025-12-04

Results Overview

Progression free survival (PFS) Note: For arm 2 (dMMR Cohort), the point estimate and the upper limit of the confidence interval are not able to be estimated due to insufficient events.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

813 participants

Primary outcome timeframe

Duration of time from study entry to time of progression per RECIST criteria or death due to any cause, whichever occurs first. The interquartile range for follow-up was (6.37 months, 30.62 months). The maximum for follow-up was 37.85 months.

Results posted on

2025-12-04

Participant Flow

Participant milestones

Participant milestones
Measure	(dMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(dMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	113	112	295	293
Overall Study COMPLETED	113	112	295	293
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Testing the Addition of the Immunotherapy Drug Pembrolizumab to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) in Stage III-IV or Recurrent Endometrial Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	(dMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) n=113 Participants COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(dMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) n=112 Participants COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) n=295 Participants COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) n=293 Participants COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	Total n=813 Participants Total of all reporting groups
Age, Continuous	66 years n=3 Participants	67 years n=3 Participants	65 years n=6 Participants	66 years n=3 Participants	66 years n=15 Participants
Sex: Female, Male Female	113 Participants n=3 Participants	112 Participants n=3 Participants	295 Participants n=6 Participants	293 Participants n=3 Participants	813 Participants n=15 Participants
Sex: Female, Male Male	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=3 Participants	0 Participants n=15 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=3 Participants	5 Participants n=3 Participants	16 Participants n=6 Participants	21 Participants n=3 Participants	48 Participants n=15 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	99 Participants n=3 Participants	106 Participants n=3 Participants	273 Participants n=6 Participants	263 Participants n=3 Participants	741 Participants n=15 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants n=3 Participants	1 Participants n=3 Participants	6 Participants n=6 Participants	9 Participants n=3 Participants	24 Participants n=15 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=3 Participants	0 Participants n=3 Participants	2 Participants n=6 Participants	2 Participants n=3 Participants	6 Participants n=15 Participants
Race (NIH/OMB) Asian	4 Participants n=3 Participants	3 Participants n=3 Participants	14 Participants n=6 Participants	17 Participants n=3 Participants	38 Participants n=15 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=3 Participants	0 Participants n=3 Participants	3 Participants n=6 Participants	1 Participants n=3 Participants	4 Participants n=15 Participants
Race (NIH/OMB) Black or African American	9 Participants n=3 Participants	11 Participants n=3 Participants	51 Participants n=6 Participants	45 Participants n=3 Participants	116 Participants n=15 Participants
Race (NIH/OMB) White	86 Participants n=3 Participants	92 Participants n=3 Participants	212 Participants n=6 Participants	212 Participants n=3 Participants	602 Participants n=15 Participants
Race (NIH/OMB) More than one race	0 Participants n=3 Participants	0 Participants n=3 Participants	1 Participants n=6 Participants	1 Participants n=3 Participants	2 Participants n=15 Participants
Race (NIH/OMB) Unknown or Not Reported	12 Participants n=3 Participants	6 Participants n=3 Participants	12 Participants n=6 Participants	15 Participants n=3 Participants	45 Participants n=15 Participants

PRIMARY outcome

Timeframe: Duration of time from study entry to time of progression per RECIST criteria or death due to any cause, whichever occurs first. The interquartile range for follow-up was (6.37 months, 30.62 months). The maximum for follow-up was 37.85 months.

Population: Randomized population (with determinate MMR status)

Progression free survival (PFS) Note: For arm 2 (dMMR Cohort), the point estimate and the upper limit of the confidence interval are not able to be estimated due to insufficient events.

Outcome measures

Outcome measures
Measure	(dMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) n=112 Participants COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(dMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) n=113 Participants COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) n=295 Participants COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) n=293 Participants COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.
Progression-free Survival (PFS)	NA Months Interval 30.6 to The point estimate and the upper limit of the confidence interval are not able to be estimated due to insufficient events.	7.6 Months Interval 6.4 to 9.9	8.7 Months Interval 8.4 to 10.7	11.7 Months Interval 11.0 to 15.0

SECONDARY outcome

Timeframe: For the adverse event time frame, the interquartile range was (0.79 months, 3.42 months); the maximum was 28.39 months.

Population: All randomized patients

Assessed by Common Terminology Criteria for Adverse Events (CTCAE V5.0). The endpoint is the count of participants with an adverse event of grade 3 (or higher) by treatment group.

Outcome measures

Outcome measures
Measure	(dMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) n=109 Participants COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(dMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) n=106 Participants COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) n=274 Participants COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) n=276 Participants COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.
Adverse Events With Grade 3 (or Higher)	68 Participants	50 Participants	124 Participants	151 Participants

SECONDARY outcome

Timeframe: For the time frame for tumor response, the interquartile range was (2.27 months, 8.66 months) and the maximum was 36.37 months.

Population: Randomized patients with measurable disease

Assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1.

Outcome measures

Outcome measures
Measure	(dMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) n=92 Participants COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(dMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) n=92 Participants COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) n=234 Participants COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) n=212 Participants COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.
Objective Tumor Response	75 Participants	65 Participants	136 Participants	150 Participants

SECONDARY outcome

Timeframe: For the duration of objective response, the interquartile range is (4.24 months, 7.92 months); the maximum is 28.68 months.

Population: Randomized patients with objective tumor response

The time difference between the dates of first response and first progression; patients who do not progress are considered censored. Note: for Arm 2 (dMMR Cohort), the upper limit of the confidence interval is not able to be estimated due to an insufficient number of events.

Outcome measures

Outcome measures
Measure	(dMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) n=75 Participants COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(dMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) n=65 Participants COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) n=136 Participants COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) n=150 Participants COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.
Duration of Objective Response	28.7 Months Interval 20.2 to The upper limit of the confidence interval is not able to be estimated due to an insufficient number of events.	6.2 Months Interval 4.3 to 9.2	6.2 Months Interval 4.8 to 6.5	9.2 Months Interval 7.1 to 14.7

SECONDARY outcome

Timeframe: Time from study entry to time of death or the date of last contact, assessed up to 5 years

Overall Survival (OS). This endpoint will be assessed by Kaplan-Meier.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 0-54 weeks from start of treatment

Population: The pMMR patients who provided baseline and at least one follow-up QOL assessment.

QoL are collected in pMMR patients only and measured with the Function Assessment of Cancer Therapy -Endometrial Trial Outcome Index (FACT En-TOI). The FACT-En TOI scores range 0 - 120 with a larger score suggesting better or favorable state of QOL.

Outcome measures

Outcome measures
Measure	(dMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) n=248 Participants COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(dMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) n=254 Participants COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.
Quality of Life (QoL) in pMMR Patients Only 30 weeks	94.6 score Standard Deviation 15.7	95.7 score Standard Deviation 16.6	—	—
Quality of Life (QoL) in pMMR Patients Only Baseline	95.3 score Standard Deviation 16.7	94.5 score Standard Deviation 18.0	—	—
Quality of Life (QoL) in pMMR Patients Only 6 weeks	92.0 score Standard Deviation 15.5	94.1 score Standard Deviation 15.1	—	—
Quality of Life (QoL) in pMMR Patients Only 18 weeks	90.3 score Standard Deviation 16.2	93.4 score Standard Deviation 15.5	—	—
Quality of Life (QoL) in pMMR Patients Only 54 weeks	96.8 score Standard Deviation 15.0	93.5 score Standard Deviation 18.2	—	—

SECONDARY outcome

Timeframe: IHC testing values (for both central and institutional) were collected at baseline.

Population: Patients from Japan were excluded. Otherwise all patients with a valid institutional MMR IHC status and a valid centralized MMR IHC status at baseline.

Concordance between institutional MMR IHC testing and centralized MMR IHC. The concordance of institutional MMR IHC testing and centralized MMR IHC will be characterized by agreement statistics including the kappa statistic (e.g. Cohen's kappa coefficient).

Outcome measures

Outcome measures
Measure	(dMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) n=377 Participants COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(dMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) n=375 Participants COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin) COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.	(pMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin) COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.
Concordance Between Institutional Mismatch Repair (MMR) Immunohistochemistry (IHC) Testing and Centralized MMR IHC	0.8944 agreement score Interval 0.8438 to 0.945	0.9197 agreement score Interval 0.875 to 0.9644	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 0-54 weeks from start of treatment

Patient-reported neurotoxicity will be measured with FACT/GOG-Ntx subscale (short form).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 5 years

Will assess the effect of pembrolizumab on PFS and OS by PD-L1 (combined positive score \[CPS\]) within proficient MMR (pMMR) and deficient MMR (dMMR) populations. The effectiveness of pembrolizumab will be compared by PD-L1 status (CPS). A formal test will be conducted by examining the interaction term between pembrolizumab treatment (yes or no) with PD-L1 status. The association between PD-L1 CPS status and MMR IHC status will be assessed with odds ratios. A test may be conducted with a Fisher's Exact Test, and confidence intervals will be provided.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 5 years

Measures of association between PD-L1 IHC (CPS) and MMR IHC status. The concordance of institutional MMR IHC testing and centralized MMR IHC will be characterized by agreement statistics such as kappa statistics (e.g. Cohen's kappa coefficient).

Outcome measures

Outcome data not reported

Adverse Events

(dMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin)

Serious events: 50 serious events

Other events: 105 other events

Deaths: 16 deaths

(dMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin)

Serious events: 66 serious events

Other events: 107 other events

Deaths: 7 deaths

(pMMR Cohort): Arm 1: Active Comparator (Placebo, Paclitaxel, Carboplatin)

Serious events: 125 serious events

Other events: 256 other events

Deaths: 47 deaths

(pMMR Cohort): Arm 2: Experimental (Pembrolizumab, Paclitaxel, Carboplatin)

Serious events: 152 serious events

Other events: 258 other events

Deaths: 42 deaths

Serious adverse events

Other adverse events

Additional Information

Christopher Purdy on behalf of Mike Sill, PhD

NRG Oncology

Phone: (716) 845-1300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60