Trial Outcomes & Findings for Lenvatinib in Combination With Pembrolizumab Versus Treatment of Physician's Choice in Participants With Advanced Endometrial Cancer (MK-3475-775/E7080-G000-309 Per Merck Standard Convention [KEYNOTE-775]) (NCT NCT03517449)

Last Updated: 2025-06-15

Results Overview

PFS was defined as the time from the date of randomization to the date of the first documentation of disease progression, as determined by Blinded Independent Central Review (BICR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter \[mm\]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

827 participants

Primary outcome timeframe

From the date of randomization to the date of the first documentation of disease progression or death, whichever occurred first or up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)

Results posted on

2025-06-15

Participant Flow

Participants took part in the study at 167 investigative sites in Argentina, Australia, Brazil, Canada, Colombia, France, Germany, Ireland, Israel, Italy, Japan, Korea, Mexico, New Zealand, Poland, Russia, Spain, Taiwan, Turkey, United Kingdom and the United States. Results in this summary are reported based on the primary completion date (26 October 2020) of the study.

A total of 1178 participants were screened, of which 351 were screen failures and 827 were enrolled and randomized, out of which 794 participants were treated.

Participant milestones

Participant milestones
Measure	Lenvatinib 20 mg + Pembrolizumab 200 mg Participants with Endometrial cancer (EC) received lenvatinib 20 milligrams (mg) orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study.	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel Participants with EC received either doxorubicin 60 milligrams per square meter (mg/m\^2) intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m\^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m\^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
Overall Study STARTED	411	416
Overall Study Treated	406	388
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	411	416

Reasons for withdrawal

Reasons for withdrawal
Measure	Lenvatinib 20 mg + Pembrolizumab 200 mg Participants with Endometrial cancer (EC) received lenvatinib 20 milligrams (mg) orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study.	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel Participants with EC received either doxorubicin 60 milligrams per square meter (mg/m\^2) intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m\^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m\^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
Overall Study Death	184	236
Overall Study Lost to Follow-up	0	2
Overall Study Withdrawal by Subject	7	26
Overall Study Participants Ongoing	220	152

Baseline Characteristics

Lenvatinib in Combination With Pembrolizumab Versus Treatment of Physician's Choice in Participants With Advanced Endometrial Cancer (MK-3475-775/E7080-G000-309 Per Merck Standard Convention [KEYNOTE-775])

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lenvatinib 20 mg + Pembrolizumab 200 mg n=411 Participants Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study.	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel n=416 Participants Participants with EC received either doxorubicin 60 mg/m\^2 intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m\^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m\^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.	Total n=827 Participants Total of all reporting groups
Age, Continuous	63.2 Years STANDARD_DEVIATION 9.1 • n=5 Participants	63.8 Years STANDARD_DEVIATION 9.2 • n=7 Participants	63.5 Years STANDARD_DEVIATION 9.1 • n=5 Participants
Sex: Female, Male Female	411 Participants n=5 Participants	416 Participants n=7 Participants	827 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	60 Participants n=5 Participants	73 Participants n=7 Participants	133 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	308 Participants n=5 Participants	287 Participants n=7 Participants	595 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	43 Participants n=5 Participants	56 Participants n=7 Participants	99 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) Asian	85 Participants n=5 Participants	92 Participants n=7 Participants	177 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	17 Participants n=5 Participants	14 Participants n=7 Participants	31 Participants n=5 Participants
Race (NIH/OMB) White	261 Participants n=5 Participants	246 Participants n=7 Participants	507 Participants n=5 Participants
Race (NIH/OMB) More than one race	7 Participants n=5 Participants	13 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	36 Participants n=5 Participants	44 Participants n=7 Participants	80 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of randomization to the date of the first documentation of disease progression or death, whichever occurred first or up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)

Population: The ITT population included all randomized participants.

Outcome measures

Outcome measures
Measure	Lenvatinib 20 mg + Pembrolizumab 200 mg n=411 Participants Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study.	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel n=416 Participants Participants with EC received either doxorubicin 60 mg/m\^2 intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m\^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m\^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
Progression-free Survival (PFS)	7.2 Months Interval 5.7 to 7.6	3.8 Months Interval 3.6 to 4.2

PRIMARY outcome

Timeframe: From the date of randomization until the date of death from any cause or up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)

Population: The ITT population included all randomized participants.

OS was defined as the time from the date of randomization to the date of death due to any cause. Participants who were lost to follow-up and those who were alive at the date of data cut-off were censored at the date the participant was last known alive, or date of data cut-off, whichever occurred first.

Outcome measures

Outcome measures
Measure	Lenvatinib 20 mg + Pembrolizumab 200 mg n=411 Participants Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study.	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel n=416 Participants Participants with EC received either doxorubicin 60 mg/m\^2 intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m\^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m\^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
Overall Survival (OS)	18.3 Months Interval 15.2 to 20.5	11.4 Months Interval 10.5 to 12.9

SECONDARY outcome

Timeframe: From date of randomization up to first documentation of PD or date of death, whichever occurred first up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)

Population: The ITT population included all randomized participants.

ORR was defined as the percentage of participants who had best overall response of either complete response (CR) or partial response (PR) as determined by BICR per RECIST 1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (\<) 10mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Outcome measures
Measure	Lenvatinib 20 mg + Pembrolizumab 200 mg n=411 Participants Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study.	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel n=416 Participants Participants with EC received either doxorubicin 60 mg/m\^2 intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m\^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m\^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
Objective Response Rate (ORR)	31.9 Percentage of participants Interval 27.4 to 36.6	14.7 Percentage of participants Interval 11.4 to 18.4

SECONDARY outcome

Timeframe: At baseline (prior to first dose of study drug), on Day 1 of each subsequent cycle (cycle length of either 21 or 28 days), and at the post-treatment visit (up to 5 years and 5 months)

EORTC QLQ-C30 was a questionnaire which included 30 questions that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores are transformed to a range of 0 to 100 using a standard EORTC algorithm. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem. Data for this outcome measure will be reported after study completion.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)

Population: Safety analysis population included all randomized participants who received at least 1 dose of study treatment.

TEAEs was defined as AEs that occurred (or worsened, if present at Baseline) after the first dose of study drug through 28 days after the last dose of study drug. AE was defined as any untoward medical occurrence in a participants or clinical study participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. A SAE was defined as any untoward medical occurrence at any dose if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. irAE was defined as any unfavorable and unintended immune-related sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.

Outcome measures

Outcome measures
Measure	Lenvatinib 20 mg + Pembrolizumab 200 mg n=406 Participants Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study.	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel n=388 Participants Participants with EC received either doxorubicin 60 mg/m\^2 intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m\^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m\^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Immune-Related Adverse Events (irAEs) Participants With TEAEs	405 Participants	386 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Immune-Related Adverse Events (irAEs) Participants With SAEs	214 Participants	118 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Immune-Related Adverse Events (irAEs) Participants With irAEs	273 Participants	17 Participants

SECONDARY outcome

Timeframe: From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)

Population: Safety analysis population included all randomized participants who received at least 1 dose of study treatment.

TEAEs was defined as those AEs that occurred (or worsened, if present at Baseline) after the first dose of study drug through 30 days after the last dose of study drug. An AE was defined as any untoward medical occurrence in a participants or clinical study participant temporally associated with the use of study treatment, whether or not considered related to the study treatment.

Outcome measures

Outcome measures
Measure	Lenvatinib 20 mg + Pembrolizumab 200 mg n=406 Participants Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study.	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel n=388 Participants Participants with EC received either doxorubicin 60 mg/m\^2 intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m\^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m\^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
Percentage of Participants Discontinued Study Treatment Due to TEAEs	33.0 Percentage of participants	8.0 Percentage of participants

SECONDARY outcome

Timeframe: From the date of randomization to the date of discontinuation of study treatment due to TEAEs (up to 5 years 5 months)

Time to treatment failure due to toxicity was defined as the time from the date of randomization to the date a participant discontinued study treatment due to TEAEs. Data for this outcome measure will be reported after study completion.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1: 0.5-10 hours post-dose; Cycle 1 Day 15: 0-12 hours post-dose; Cycle 2 Day 1: 0.5-10 hours post-dose (each cycle length=21 days)

Population: The population pharmacokinetic analysis set includes all the participants who have received at least 1 dose of study treatment with documented dosing history in the lenvatinib plus pembrolizumab arm, and have measurable plasma levels of lenvatinib. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Sparse pharmacokinetic (PK) samples were collected and analyzed using a population PK approach to estimate PK parameters. Individual predicted CL/F for lenvatinib was then derived from the PK model. The data was collected and analyzed for lenvatinib plus pembrolizumab arm only.

Outcome measures

Outcome measures
Measure	Lenvatinib 20 mg + Pembrolizumab 200 mg n=403 Participants Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study.	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel Participants with EC received either doxorubicin 60 mg/m\^2 intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m\^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m\^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
Model Predicted Apparent Total Clearance (CL/F) for Lenvatinib	4.69 liter per hour (L/h) Standard Deviation 1.39	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1: 0.5-10 hours post-dose; Cycle 1 Day 15: 0-12 hours post-dose; Cycle 2 Day 1: 0.5-10 hours post-dose (each cycle length=21 days)

Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Individual predicted AUC for lenvatinib was then derived from the PK model. The data was collected and analyzed for lenvatinib plus pembrolizumab arm only.

Outcome measures

Outcome measures
Measure	Lenvatinib 20 mg + Pembrolizumab 200 mg n=403 Participants Participants with EC received lenvatinib 20 mg orally, once daily, plus pembrolizumab 200 mg intravenously, every 3 weeks in each 21-day cycle. Participants continued to receive treatment until disease progression, development of unacceptable toxicity, withdrawal of consent, completion of 35 treatments (approximately 2 years) with pembrolizumab, or sponsor termination of the study.	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel Participants with EC received either doxorubicin 60 mg/m\^2 intravenously, every 3 weeks, in each 21-day treatment cycle, or paclitaxel 80 mg/m\^2 intravenously, weekly (3 weeks on/1 week off), in each 28-day treatment cycle. Participants continued to receive treatment until a lifetime cumulative dose of 500 mg/m\^2 doxorubicin, a maximum dose of paclitaxel per standard of care, or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
Model Predicted Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib	4134 nanogramhour per milliliter (ngh/mL) Standard Deviation 1350	—

Adverse Events

Lenvatinib 20 mg + Pembrolizumab 200 mg

Serious events: 214 serious events

Other events: 404 other events

Deaths: 184 deaths

Treatment of Physician's Choice: (TPC) Doxorubicin or Paclitaxel

Serious events: 118 serious events

Other events: 379 other events

Deaths: 236 deaths

Serious adverse events

Other adverse events

Additional Information

Eisai Medical Information

Eisai Inc.

Phone: 1-888-274-2378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place