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])

• ClinicalTrials.gov Identifier: NCT03517449
• Recruitment Status: Active, not recruiting
• First Posted: May 7, 2018
• Results First Posted: November 17, 2021
• Last Update Posted: October 18, 2023
• Sponsor: Eisai Inc.
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Eisai Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Endometrial Neoplasms
• Interventions: Drug: Pembrolizumab; Drug: Lenvatinib; Drug: Paclitaxel; Drug: Doxorubicin
• Enrollment: 827

Participant Flow

Recruitment Details	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.
Pre-assignment Details	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.

Arm/Group Title	Lenvatinib 20 mg + Pembrolizumab 200 mg	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
Arm/Group Description	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.	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.
Period Title: Overall Study
Started	411	416
Treated	406	388
Completed	0	0
Not Completed	411	416
Reason Not Completed
Death	184	236
Lost to Follow-up	0	2
Withdrawal by Subject	7	26
Participants Ongoing	220	152

Baseline Characteristics

Arm/Group Title		Lenvatinib 20 mg + Pembrolizumab 200 mg	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel	Total
Arm/Group Description		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.	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 of all reporting groups
Overall Number of Baseline Participants		411	416	827
Baseline Analysis Population Description		The Intention-to-treat (ITT) population included all randomized participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	411 participants	416 participants	827 participants
		63.2 (9.1)	63.8 (9.2)	63.5 (9.1)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	411 participants	416 participants	827 participants
	Female	411 100.0%	416 100.0%	827 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	411 participants	416 participants	827 participants
	Hispanic or Latino	60 14.6%	73 17.5%	133 16.1%
	Not Hispanic or Latino	308 74.9%	287 69.0%	595 71.9%
	Unknown or Not Reported	43 10.5%	56 13.5%	99 12.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	411 participants	416 participants	827 participants
	American Indian or Alaska Native	4 1.0%	7 1.7%	11 1.3%
	Asian	85 20.7%	92 22.1%	177 21.4%
	Native Hawaiian or Other Pacific Islander	1 0.2%	0 0.0%	1 0.1%
	Black or African American	17 4.1%	14 3.4%	31 3.7%
	White	261 63.5%	246 59.1%	507 61.3%
	More than one race	7 1.7%	13 3.1%	20 2.4%
	Unknown or Not Reported	36 8.8%	44 10.6%	80 9.7%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants.

Arm/Group Title	Lenvatinib 20 mg + Pembrolizumab 200 mg	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
Arm/Group Description:	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.	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 Number of Participants Analyzed	411	416
Median (95% Confidence Interval); Unit of Measure: Months
	7.2; (5.7 to 7.6)	3.8; (3.6 to 4.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenvatinib 20 mg + Pembrolizumab 200 mg, Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95%; 0.47 to 0.66
	Estimation Comments	Regression, Cox method

2. Primary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants.

Arm/Group Title	Lenvatinib 20 mg + Pembrolizumab 200 mg	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
Arm/Group Description:	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.	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 Number of Participants Analyzed	411	416
Median (95% Confidence Interval); Unit of Measure: Months
	18.3; (15.2 to 20.5)	11.4; (10.5 to 12.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenvatinib 20 mg + Pembrolizumab 200 mg, Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; 0.51 to 0.75
	Estimation Comments	Regression, Cox method

3. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants.

Arm/Group Title	Lenvatinib 20 mg + Pembrolizumab 200 mg	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
Arm/Group Description:	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.	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 Number of Participants Analyzed	411	416
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	31.9; (27.4 to 36.6)	14.7; (11.4 to 18.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenvatinib 20 mg + Pembrolizumab 200 mg, Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Miettinen & Nurminen method
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percent
	Estimated Value	17.2
	Confidence Interval	(2-Sided) 95%; 11.5 to 22.9
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Health-Related Quality of Life (HRQoL) Assessed by European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQC30) Score
Description	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 (anticipated study completion date is November 2023).
Time Frame	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)

Outcome Measure Data Not Reported

5. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Immune-Related Adverse Events (irAEs)
Description	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.
Time Frame	From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lenvatinib 20 mg + Pembrolizumab 200 mg	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
Arm/Group Description:	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.	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 Number of Participants Analyzed	406	388
Measure Type: Count of Participants; Unit of Measure: Participants
Participants With TEAEs	405 99.8%	386 99.5%
Participants With SAEs	214 52.7%	118 30.4%
Participants With irAEs	273 67.2%	17 4.4%

6. Secondary Outcome

Title	Percentage of Participants Discontinued Study Treatment Due to TEAEs
Description	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.
Time Frame	From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lenvatinib 20 mg + Pembrolizumab 200 mg	Treatment of Physician's Choice (TPC): Doxorubicin or Paclitaxel
Arm/Group Description:	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.	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 Number of Participants Analyzed	406	388
Measure Type: Number; Unit of Measure: Percentage of participants
	33.0	8.0

7. Secondary Outcome

Title	Time to Treatment Failure Due to Toxicity
Description	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 (anticipated study completion date is November 2023).
Time Frame	From the date of randomization to the date of discontinuation of study treatment due to TEAEs (up to 5 years 5 months)

Outcome Measure Data Not Reported

8. Secondary Outcome

Title	Model Predicted Apparent Total Clearance (CL/F) for Lenvatinib
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lenvatinib 20 mg + Pembrolizumab 200 mg
Arm/Group Description:	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.
Overall Number of Participants Analyzed	403
Mean (Standard Deviation); Unit of Measure: liter per hour (L/h)
	4.69 (1.39)

9. Secondary Outcome

Title	Model Predicted Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lenvatinib 20 mg + Pembrolizumab 200 mg
Arm/Group Description:	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.
Overall Number of Participants Analyzed	403
Mean (Standard Deviation); Unit of Measure: nanogram*hour per milliliter (ng*h/mL)
	4134 (1350)

Adverse Events

Time Frame	From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Lenvatinib 20 mg + Pembrolizumab 200 mg	Treatment of Physician's Choice: (TPC) Doxorubicin or Paclitaxel
Arm/Group Description	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.	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.
All-Cause Mortality
	Lenvatinib 20 mg + Pembrolizumab 200 mg	Treatment of Physician's Choice: (TPC) Doxorubicin or Paclitaxel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	184/406 (45.32%)	236/388 (60.82%)
Serious Adverse Events
	Lenvatinib 20 mg + Pembrolizumab 200 mg	Treatment of Physician's Choice: (TPC) Doxorubicin or Paclitaxel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	214/406 (52.71%)	118/388 (30.41%)
Blood and lymphatic system disorders
Anaemia † 1	1/406 (0.25%)	9/388 (2.32%)
Febrile bone marrow aplasia † 1	0/406 (0.00%)	1/388 (0.26%)
Febrile neutropenia † 1	2/406 (0.49%)	16/388 (4.12%)
Leukocytosis † 1	0/406 (0.00%)	1/388 (0.26%)
Leukopenia † 1	0/406 (0.00%)	2/388 (0.52%)
Neutropenia † 1	1/406 (0.25%)	7/388 (1.80%)
Neutrophilia † 1	0/406 (0.00%)	1/388 (0.26%)
Pancytopenia † 1	1/406 (0.25%)	0/388 (0.00%)
Thrombocytopenia † 1	1/406 (0.25%)	1/388 (0.26%)
Thrombotic microangiopathy † 1	1/406 (0.25%)	0/388 (0.00%)
Cardiac disorders
Acute coronary syndrome † 1	2/406 (0.49%)	0/388 (0.00%)
Acute myocardial infarction † 1	3/406 (0.74%)	0/388 (0.00%)
Atrial fibrillation † 1	1/406 (0.25%)	2/388 (0.52%)
Bundle branch block left † 1	1/406 (0.25%)	0/388 (0.00%)
Cardiac failure † 1	0/406 (0.00%)	3/388 (0.77%)
Cardiac failure congestive † 1	0/406 (0.00%)	2/388 (0.52%)
Cardiogenic shock † 1	0/406 (0.00%)	2/388 (0.52%)
Left ventricular dysfunction † 1	0/406 (0.00%)	1/388 (0.26%)
Myocardial infarction † 1	1/406 (0.25%)	0/388 (0.00%)
Myocarditis † 1	1/406 (0.25%)	0/388 (0.00%)
Pericardial effusion † 1	1/406 (0.25%)	0/388 (0.00%)
Right ventricular dysfunction † 1	1/406 (0.25%)	0/388 (0.00%)
Sinus tachycardia † 1	1/406 (0.25%)	0/388 (0.00%)
Stress cardiomyopathy † 1	1/406 (0.25%)	0/388 (0.00%)
Supraventricular tachycardia † 1	0/406 (0.00%)	2/388 (0.52%)
Toxic cardiomyopathy † 1	0/406 (0.00%)	1/388 (0.26%)
Ventricular fibrillation † 1	1/406 (0.25%)	0/388 (0.00%)
Endocrine disorders
Adrenal insufficiency † 1	3/406 (0.74%)	0/388 (0.00%)
Adrenocorticotropic hormone deficiency † 1	1/406 (0.25%)	0/388 (0.00%)
Hyperthyroidism † 1	3/406 (0.74%)	0/388 (0.00%)
Hypophysitis † 1	1/406 (0.25%)	0/388 (0.00%)
Hypothyroidism † 1	2/406 (0.49%)	0/388 (0.00%)
Eye disorders
Iridocyclitis † 1	1/406 (0.25%)	0/388 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	4/406 (0.99%)	1/388 (0.26%)
Abdominal pain lower † 1	1/406 (0.25%)	0/388 (0.00%)
Anal fissure † 1	1/406 (0.25%)	0/388 (0.00%)
Ascites † 1	2/406 (0.49%)	2/388 (0.52%)
Colitis † 1	7/406 (1.72%)	1/388 (0.26%)
Colonic fistula † 1	0/406 (0.00%)	2/388 (0.52%)
Constipation † 1	3/406 (0.74%)	0/388 (0.00%)
Diarrhoea † 1	10/406 (2.46%)	3/388 (0.77%)
Diverticular perforation † 1	1/406 (0.25%)	0/388 (0.00%)
Duodenal obstruction † 1	0/406 (0.00%)	1/388 (0.26%)
Enterocolitis † 1	1/406 (0.25%)	0/388 (0.00%)
Gastritis erosive † 1	1/406 (0.25%)	0/388 (0.00%)
Gastrointestinal haemorrhage † 1	2/406 (0.49%)	0/388 (0.00%)
Gastrointestinal perforation † 1	2/406 (0.49%)	0/388 (0.00%)
Gastrointestinal toxicity † 1	0/406 (0.00%)	1/388 (0.26%)
Gastrooesophageal reflux disease † 1	1/406 (0.25%)	0/388 (0.00%)
Ileus † 1	4/406 (0.99%)	0/388 (0.00%)
Immune-mediated pancreatitis † 1	1/406 (0.25%)	0/388 (0.00%)
Intestinal fistula † 1	1/406 (0.25%)	0/388 (0.00%)
Intestinal obstruction * 1	5/406 (1.23%)	3/388 (0.77%)
Intestinal perforation † 1	3/406 (0.74%)	0/388 (0.00%)
Large intestinal obstruction † 1	1/406 (0.25%)	0/388 (0.00%)
Large intestine perforation † 1	2/406 (0.49%)	0/388 (0.00%)
Lower gastrointestinal haemorrhage † 1	1/406 (0.25%)	0/388 (0.00%)
Lower gastrointestinal perforation † 1	1/406 (0.25%)	0/388 (0.00%)
Malignant gastrointestinal obstruction † 1	1/406 (0.25%)	0/388 (0.00%)
Mechanical ileus † 1	1/406 (0.25%)	0/388 (0.00%)
Nausea † 1	3/406 (0.74%)	1/388 (0.26%)
Pancreatitis acute † 1	2/406 (0.49%)	0/388 (0.00%)
Proctalgia † 1	1/406 (0.25%)	0/388 (0.00%)
Rectal perforation † 1	1/406 (0.25%)	0/388 (0.00%)
Small intestinal obstruction † 1	3/406 (0.74%)	2/388 (0.52%)
Stomatitis † 1	0/406 (0.00%)	1/388 (0.26%)
Subileus † 1	2/406 (0.49%)	1/388 (0.26%)
Umbilical hernia † 1	1/406 (0.25%)	0/388 (0.00%)
Vomiting † 1	9/406 (2.22%)	3/388 (0.77%)
General disorders
Asthenia † 1	3/406 (0.74%)	2/388 (0.52%)
Catheter site inflammation † 1	0/406 (0.00%)	1/388 (0.26%)
Condition aggravated † 1	0/406 (0.00%)	1/388 (0.26%)
Death † 1	5/406 (1.23%)	3/388 (0.77%)
Device related thrombosis † 1	1/406 (0.25%)	0/388 (0.00%)
Fatigue † 1	2/406 (0.49%)	0/388 (0.00%)
General physical health deterioration † 1	3/406 (0.74%)	1/388 (0.26%)
Generalised oedema † 1	2/406 (0.49%)	0/388 (0.00%)
Hyperpyrexia † 1	0/406 (0.00%)	1/388 (0.26%)
Mucosal inflammation † 1	1/406 (0.25%)	0/388 (0.00%)
Multiple organ dysfunction syndrome † 1	1/406 (0.25%)	2/388 (0.52%)
Oedema peripheral † 1	1/406 (0.25%)	1/388 (0.26%)
Perforated ulcer † 1	1/406 (0.25%)	0/388 (0.00%)
Pyrexia † 1	8/406 (1.97%)	3/388 (0.77%)
Hepatobiliary disorders
Bile duct stone † 1	1/406 (0.25%)	0/388 (0.00%)
Biliary obstruction † 1	1/406 (0.25%)	0/388 (0.00%)
Cholangitis † 1	3/406 (0.74%)	0/388 (0.00%)
Cholecystitis † 1	7/406 (1.72%)	0/388 (0.00%)
Cholecystitis acute † 1	1/406 (0.25%)	0/388 (0.00%)
Hepatic failure † 1	1/406 (0.25%)	0/388 (0.00%)
Hepatic function abnormal † 1	2/406 (0.49%)	0/388 (0.00%)
Hepatitis † 1	1/406 (0.25%)	0/388 (0.00%)
Hepatobiliary disease † 1	0/406 (0.00%)	1/388 (0.26%)
Hepatotoxicity † 1	1/406 (0.25%)	0/388 (0.00%)
Immune-mediated hepatitis † 1	2/406 (0.49%)	0/388 (0.00%)
Liver disorder † 1	2/406 (0.49%)	0/388 (0.00%)
Immune system disorders
Anaphylactic reaction † 1	1/406 (0.25%)	0/388 (0.00%)
Anaphylactic shock † 1	1/406 (0.25%)	0/388 (0.00%)
Hypersensitivity † 1	3/406 (0.74%)	0/388 (0.00%)
Infections and infestations
Abdominal sepsis † 1	0/406 (0.00%)	1/388 (0.26%)
Appendicitis † 1	2/406 (0.49%)	0/388 (0.00%)
Appendicitis perforated † 1	1/406 (0.25%)	0/388 (0.00%)
Arthritis bacterial † 1	1/406 (0.25%)	0/388 (0.00%)
Bacteraemia † 1	1/406 (0.25%)	2/388 (0.52%)
Bacterial infection † 1	1/406 (0.25%)	0/388 (0.00%)
Cellulitis † 1	0/406 (0.00%)	2/388 (0.52%)
Cystitis † 1	1/406 (0.25%)	0/388 (0.00%)
Device related infection † 1	2/406 (0.49%)	2/388 (0.52%)
Diarrhoea infectious † 1	1/406 (0.25%)	0/388 (0.00%)
Encephalitis † 1	1/406 (0.25%)	0/388 (0.00%)
Escherichia bacteraemia † 1	1/406 (0.25%)	0/388 (0.00%)
Gastroenteritis † 1	3/406 (0.74%)	1/388 (0.26%)
Gastroenteritis Escherichia coli † 1	1/406 (0.25%)	0/388 (0.00%)
Gastroenteritis norovirus † 1	1/406 (0.25%)	0/388 (0.00%)
Infected fistula † 1	1/406 (0.25%)	0/388 (0.00%)
Infection † 1	2/406 (0.49%)	1/388 (0.26%)
Influenza † 1	2/406 (0.49%)	2/388 (0.52%)
Lower respiratory tract infection † 1	1/406 (0.25%)	0/388 (0.00%)
Meningitis bacterial † 1	1/406 (0.25%)	0/388 (0.00%)
Oesophageal candidiasis † 1	0/406 (0.00%)	1/388 (0.26%)
Pelvic abscess † 1	0/406 (0.00%)	1/388 (0.26%)
Peritonitis † 1	2/406 (0.49%)	0/388 (0.00%)
Pneumonia † 1	6/406 (1.48%)	3/388 (0.77%)
Postoperative wound infection † 1	3/406 (0.74%)	0/388 (0.00%)
Psoas abscess † 1	1/406 (0.25%)	0/388 (0.00%)
Pyelonephritis † 1	1/406 (0.25%)	1/388 (0.26%)
Pyelonephritis acute † 1	0/406 (0.00%)	1/388 (0.26%)
Retroperitoneal abscess † 1	0/406 (0.00%)	1/388 (0.26%)
Sepsis † 1	5/406 (1.23%)	5/388 (1.29%)
Septic shock † 1	0/406 (0.00%)	1/388 (0.26%)
Sialoadenitis † 1	1/406 (0.25%)	0/388 (0.00%)
Sinusitis † 1	1/406 (0.25%)	0/388 (0.00%)
Skin infection † 1	1/406 (0.25%)	0/388 (0.00%)
Staphylococcal bacteraemia † 1	1/406 (0.25%)	0/388 (0.00%)
Tonsillitis † 1	1/406 (0.25%)	0/388 (0.00%)
Upper respiratory tract infection † 1	1/406 (0.25%)	0/388 (0.00%)
Urinary tract infection † 1	13/406 (3.20%)	2/388 (0.52%)
Urosepsis † 1	1/406 (0.25%)	2/388 (0.52%)
Vaginal abscess † 1	1/406 (0.25%)	0/388 (0.00%)
Vaginal infection † 1	1/406 (0.25%)	0/388 (0.00%)
Wound infection † 1	1/406 (0.25%)	0/388 (0.00%)
Injury, poisoning and procedural complications
Craniocerebral injury † 1	1/406 (0.25%)	0/388 (0.00%)
Gastroenteritis radiation † 1	1/406 (0.25%)	0/388 (0.00%)
Postoperative ileus † 1	1/406 (0.25%)	0/388 (0.00%)
Radius fracture † 1	0/406 (0.00%)	1/388 (0.26%)
Skull fractured base † 1	1/406 (0.25%)	0/388 (0.00%)
Subdural haematoma † 1	0/406 (0.00%)	1/388 (0.26%)
Vascular procedure complication † 1	0/406 (0.00%)	1/388 (0.26%)
Wound dehiscence † 1	1/406 (0.25%)	0/388 (0.00%)
Investigations
Alanine aminotransferase increased † 1	0/406 (0.00%)	1/388 (0.26%)
Aspartate aminotransferase increased † 1	0/406 (0.00%)	1/388 (0.26%)
Blood alkaline phosphatase increased † 1	0/406 (0.00%)	1/388 (0.26%)
Blood creatine phosphokinase increased † 1	1/406 (0.25%)	0/388 (0.00%)
Blood creatinine increased † 1	1/406 (0.25%)	0/388 (0.00%)
ECG signs of myocardial ischaemia † 1	1/406 (0.25%)	0/388 (0.00%)
Ejection fraction decreased † 1	0/406 (0.00%)	1/388 (0.26%)
Electrocardiogram QT prolonged † 1	1/406 (0.25%)	0/388 (0.00%)
Lipase increased † 1	1/406 (0.25%)	0/388 (0.00%)
Transaminases increased † 1	1/406 (0.25%)	0/388 (0.00%)
Metabolism and nutrition disorders
Decreased appetite † 1	9/406 (2.22%)	0/388 (0.00%)
Dehydration † 1	5/406 (1.23%)	1/388 (0.26%)
Diabetes mellitus † 1	1/406 (0.25%)	0/388 (0.00%)
Diabetic ketoacidosis † 1	1/406 (0.25%)	0/388 (0.00%)
Electrolyte imbalance † 1	1/406 (0.25%)	0/388 (0.00%)
Hypercalcaemia † 1	1/406 (0.25%)	1/388 (0.26%)
Hyperglycaemia † 1	2/406 (0.49%)	0/388 (0.00%)
Hypochloraemia † 1	0/406 (0.00%)	1/388 (0.26%)
Hypoglycaemia † 1	1/406 (0.25%)	0/388 (0.00%)
Hypokalaemia † 1	3/406 (0.74%)	1/388 (0.26%)
Hypomagnesaemia † 1	1/406 (0.25%)	0/388 (0.00%)
Hyponatraemia † 1	2/406 (0.49%)	2/388 (0.52%)
Hypophosphataemia † 1	0/406 (0.00%)	1/388 (0.26%)
Malnutrition † 1	1/406 (0.25%)	0/388 (0.00%)
Type 1 diabetes mellitus † 1	3/406 (0.74%)	0/388 (0.00%)
Type 2 diabetes mellitus † 1	0/406 (0.00%)	1/388 (0.26%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/406 (0.25%)	0/388 (0.00%)
Arthritis † 1	2/406 (0.49%)	0/388 (0.00%)
Back pain † 1	1/406 (0.25%)	0/388 (0.00%)
Bone pain † 1	0/406 (0.00%)	1/388 (0.26%)
Fistula † 1	1/406 (0.25%)	0/388 (0.00%)
Myalgia † 1	1/406 (0.25%)	0/388 (0.00%)
Myositis † 1	2/406 (0.49%)	0/388 (0.00%)
Pain in extremity † 1	2/406 (0.49%)	0/388 (0.00%)
Pathological fracture † 1	0/406 (0.00%)	1/388 (0.26%)
Periarthritis † 1	1/406 (0.25%)	0/388 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma † 1	0/406 (0.00%)	1/388 (0.26%)
Myelodysplastic syndrome † 1	1/406 (0.25%)	0/388 (0.00%)
Plasma cell myeloma † 1	1/406 (0.25%)	0/388 (0.00%)
Tumour pain † 1	0/406 (0.00%)	1/388 (0.26%)
Nervous system disorders
Cerebral haemorrhage † 1	1/406 (0.25%)	0/388 (0.00%)
Cerebral infarction † 1	1/406 (0.25%)	0/388 (0.00%)
Cerebrovascular accident † 1	2/406 (0.49%)	3/388 (0.77%)
Encephalitis autoimmune † 1	1/406 (0.25%)	0/388 (0.00%)
Encephalopathy † 1	0/406 (0.00%)	1/388 (0.26%)
Haemorrhage intracranial † 1	1/406 (0.25%)	0/388 (0.00%)
Haemorrhagic stroke † 1	1/406 (0.25%)	0/388 (0.00%)
Headache † 1	2/406 (0.49%)	0/388 (0.00%)
Migraine † 1	1/406 (0.25%)	0/388 (0.00%)
Myasthenia gravis † 1	1/406 (0.25%)	0/388 (0.00%)
Nervous system disorder † 1	1/406 (0.25%)	0/388 (0.00%)
Neuralgia † 1	1/406 (0.25%)	0/388 (0.00%)
Optic neuritis † 1	1/406 (0.25%)	0/388 (0.00%)
Seizure † 1	0/406 (0.00%)	2/388 (0.52%)
Syncope † 1	1/406 (0.25%)	2/388 (0.52%)
Tremor † 1	1/406 (0.25%)	0/388 (0.00%)
Product Issues
Device dislocation † 1	0/406 (0.00%)	1/388 (0.26%)
Psychiatric disorders
Anxiety † 1	1/406 (0.25%)	1/388 (0.26%)
Assisted suicide † 1	1/406 (0.25%)	0/388 (0.00%)
Confusional state † 1	1/406 (0.25%)	0/388 (0.00%)
Delirium † 1	1/406 (0.25%)	1/388 (0.26%)
Renal and urinary disorders
Acute kidney injury † 1	8/406 (1.97%)	3/388 (0.77%)
Autoimmune nephritis † 1	1/406 (0.25%)	0/388 (0.00%)
Haematuria † 1	1/406 (0.25%)	1/388 (0.26%)
Haemorrhage urinary tract † 1	1/406 (0.25%)	0/388 (0.00%)
Hydronephrosis † 1	1/406 (0.25%)	0/388 (0.00%)
Nephrolithiasis † 1	0/406 (0.00%)	1/388 (0.26%)
Renal failure † 1	3/406 (0.74%)	1/388 (0.26%)
Renal injury † 1	1/406 (0.25%)	0/388 (0.00%)
Urinary tract obstruction † 1	1/406 (0.25%)	0/388 (0.00%)
Urogenital fistula † 1	1/406 (0.25%)	1/388 (0.26%)
Reproductive system and breast disorders
Female genital tract fistula † 1	3/406 (0.74%)	1/388 (0.26%)
Metrorrhagia † 1	1/406 (0.25%)	0/388 (0.00%)
Uterine haemorrhage † 1	1/406 (0.25%)	0/388 (0.00%)
Vaginal haemorrhage † 1	3/406 (0.74%)	0/388 (0.00%)
Respiratory, thoracic and mediastinal disorders
Aspiration † 1	0/406 (0.00%)	1/388 (0.26%)
Dyspnoea † 1	2/406 (0.49%)	1/388 (0.26%)
Dyspnoea exertional † 1	0/406 (0.00%)	1/388 (0.26%)
Epistaxis † 1	2/406 (0.49%)	0/388 (0.00%)
Pleural effusion † 1	1/406 (0.25%)	1/388 (0.26%)
Pneumonitis † 1	3/406 (0.74%)	0/388 (0.00%)
Pulmonary embolism † 1	4/406 (0.99%)	5/388 (1.29%)
Pulmonary hypertension † 1	1/406 (0.25%)	0/388 (0.00%)
Respiratory distress † 1	0/406 (0.00%)	1/388 (0.26%)
Respiratory failure † 1	1/406 (0.25%)	3/388 (0.77%)
Skin and subcutaneous tissue disorders
Drug eruption † 1	1/406 (0.25%)	0/388 (0.00%)
Palmar-plantar erythrodysaesthesia syndrome † 1	1/406 (0.25%)	0/388 (0.00%)
Rash † 1	1/406 (0.25%)	0/388 (0.00%)
Rash macular † 1	1/406 (0.25%)	0/388 (0.00%)
Stasis dermatitis † 1	1/406 (0.25%)	0/388 (0.00%)
Stevens-Johnson syndrome † 1	1/406 (0.25%)	0/388 (0.00%)
Toxic skin eruption † 1	1/406 (0.25%)	0/388 (0.00%)
Umbilical haemorrhage † 1	0/406 (0.00%)	1/388 (0.26%)
Vascular disorders
Aortic thrombosis † 1	1/406 (0.25%)	0/388 (0.00%)
Deep vein thrombosis † 1	1/406 (0.25%)	2/388 (0.52%)
Hypertension † 1	17/406 (4.19%)	0/388 (0.00%)
Hypotension † 1	2/406 (0.49%)	0/388 (0.00%)
Jugular vein thrombosis † 1	1/406 (0.25%)	0/388 (0.00%)
Pelvic venous thrombosis † 1	0/406 (0.00%)	1/388 (0.26%)
Thrombosis † 1	1/406 (0.25%)	0/388 (0.00%)
Vasculitis † 1	1/406 (0.25%)	0/388 (0.00%)
1 Term from vocabulary, MedDRA Version 23.1; † Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Lenvatinib 20 mg + Pembrolizumab 200 mg	Treatment of Physician's Choice: (TPC) Doxorubicin or Paclitaxel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	404/406 (99.51%)	379/388 (97.68%)
Blood and lymphatic system disorders
Anaemia † 1	105/406 (25.86%)	181/388 (46.65%)
Leukopenia † 1	28/406 (6.90%)	49/388 (12.63%)
Lymphopenia † 1	25/406 (6.16%)	30/388 (7.73%)
Neutropenia † 1	29/406 (7.14%)	124/388 (31.96%)
Thrombocytopenia † 1	43/406 (10.59%)	25/388 (6.44%)
Endocrine disorders
Hyperthyroidism † 1	44/406 (10.84%)	4/388 (1.03%)
Hypothyroidism † 1	231/406 (56.90%)	3/388 (0.77%)
Gastrointestinal disorders
Abdominal pain † 1	79/406 (19.46%)	52/388 (13.40%)
Abdominal pain upper † 1	53/406 (13.05%)	27/388 (6.96%)
Constipation † 1	104/406 (25.62%)	96/388 (24.74%)
Diarrhoea † 1	215/406 (52.96%)	75/388 (19.33%)
Dry mouth † 1	40/406 (9.85%)	11/388 (2.84%)
Dyspepsia † 1	27/406 (6.65%)	19/388 (4.90%)
Gastritis † 1	21/406 (5.17%)	2/388 (0.52%)
Gastrooesophageal reflux disease † 1	27/406 (6.65%)	8/388 (2.06%)
Haemorrhoids † 1	23/406 (5.67%)	7/388 (1.80%)
Nausea † 1	200/406 (49.26%)	178/388 (45.88%)
Stomatitis † 1	78/406 (19.21%)	46/388 (11.86%)
Vomiting † 1	145/406 (35.71%)	79/388 (20.36%)
General disorders
Asthenia † 1	94/406 (23.15%)	93/388 (23.97%)
Fatigue † 1	132/406 (32.51%)	107/388 (27.58%)
Malaise † 1	25/406 (6.16%)	19/388 (4.90%)
Mucosal inflammation † 1	48/406 (11.82%)	38/388 (9.79%)
Oedema peripheral † 1	48/406 (11.82%)	35/388 (9.02%)
Pyrexia † 1	54/406 (13.30%)	26/388 (6.70%)
Infections and infestations
Nasopharyngitis † 1	14/406 (3.45%)	24/388 (6.19%)
Urinary tract infection † 1	95/406 (23.40%)	38/388 (9.79%)
Investigations
Alanine aminotransferase increased † 1	86/406 (21.18%)	19/388 (4.90%)
Amylase increased † 1	29/406 (7.14%)	5/388 (1.29%)
Aspartate aminotransferase increased † 1	80/406 (19.70%)	16/388 (4.12%)
Blood alkaline phosphatase increased † 1	50/406 (12.32%)	14/388 (3.61%)
Blood bilirubin increased † 1	22/406 (5.42%)	7/388 (1.80%)
Blood cholesterol increased † 1	34/406 (8.37%)	7/388 (1.80%)
Blood creatinine increased † 1	44/406 (10.84%)	10/388 (2.58%)
Blood thyroid stimulating hormone increased † 1	52/406 (12.81%)	1/388 (0.26%)
Lipase increased † 1	44/406 (10.84%)	8/388 (2.06%)
Lymphocyte count decreased † 1	17/406 (4.19%)	23/388 (5.93%)
Neutrophil count decreased † 1	22/406 (5.42%)	94/388 (24.23%)
Platelet count decreased † 1	50/406 (12.32%)	22/388 (5.67%)
Weight decreased † 1	138/406 (33.99%)	22/388 (5.67%)
White blood cell count decreased † 1	20/406 (4.93%)	60/388 (15.46%)
Metabolism and nutrition disorders
Decreased appetite † 1	174/406 (42.86%)	82/388 (21.13%)
Dehydration † 1	21/406 (5.17%)	7/388 (1.80%)
Hypercholesterolaemia † 1	24/406 (5.91%)	7/388 (1.80%)
Hyperglycaemia † 1	36/406 (8.87%)	19/388 (4.90%)
Hypertriglyceridaemia † 1	51/406 (12.56%)	11/388 (2.84%)
Hypoalbuminaemia † 1	37/406 (9.11%)	18/388 (4.64%)
Hypokalaemia * 1	52/406 (12.81%)	26/388 (6.70%)
Hypomagnesaemia † 1	71/406 (17.49%)	26/388 (6.70%)
Hyponatraemia † 1	34/406 (8.37%)	16/388 (4.12%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	123/406 (30.30%)	31/388 (7.99%)
Back pain † 1	48/406 (11.82%)	29/388 (7.47%)
Myalgia † 1	71/406 (17.49%)	19/388 (4.90%)
Pain in extremity † 1	44/406 (10.84%)	21/388 (5.41%)
Nervous system disorders
Dizziness † 1	42/406 (10.34%)	22/388 (5.67%)
Dysgeusia † 1	40/406 (9.85%)	27/388 (6.96%)
Headache † 1	99/406 (24.38%)	34/388 (8.76%)
Neuropathy peripheral † 1	16/406 (3.94%)	22/388 (5.67%)
Psychiatric disorders
Insomnia † 1	33/406 (8.13%)	20/388 (5.15%)
Renal and urinary disorders
Dysuria † 1	22/406 (5.42%)	11/388 (2.84%)
Proteinuria † 1	117/406 (28.82%)	11/388 (2.84%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	53/406 (13.05%)	51/388 (13.14%)
Dysphonia † 1	93/406 (22.91%)	2/388 (0.52%)
Dyspnoea † 1	44/406 (10.84%)	41/388 (10.57%)
Epistaxis † 1	31/406 (7.64%)	10/388 (2.58%)
Oropharyngeal pain † 1	22/406 (5.42%)	9/388 (2.32%)
Skin and subcutaneous tissue disorders
Alopecia † 1	22/406 (5.42%)	120/388 (30.93%)
Dry skin † 1	28/406 (6.90%)	11/388 (2.84%)
Palmar-plantar erythrodysaesthesia syndrome † 1	86/406 (21.18%)	3/388 (0.77%)
Pruritus † 1	42/406 (10.34%)	12/388 (3.09%)
Rash † 1	61/406 (15.02%)	13/388 (3.35%)
Vascular disorders
Hypertension † 1	250/406 (61.58%)	20/388 (5.15%)
1 Term from vocabulary, MedDRA Version 23.1; † Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Eisai Medical Information
• Organization: Eisai Inc.
• Phone: 1-888-274-2378
• EMail: esi_oncmedinfo@eisai.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Makker V, Colombo N, Casado Herraez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D; Study 309-KEYNOTE-775 Investigators. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022 Feb 3;386(5):437-448. doi: 10.1056/NEJMoa2108330. Epub 2022 Jan 19.

• Responsible Party: Eisai Inc.
• ClinicalTrials.gov Identifier: NCT03517449
• Other Study ID Numbers: E7080-G000-309; 2017-004387-35 ( EudraCT Number ); MK3475-775 ( Other Identifier: Merck Protocol Number )
• First Submitted: April 25, 2018
• First Posted: May 7, 2018
• Results First Submitted: October 19, 2021
• Results First Posted: November 17, 2021
• Last Update Posted: October 18, 2023