Trial Outcomes & Findings for Efficacy and Safety of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) for Advanced Melanoma in Anti-Programmed Death-1/Programmed Death-Ligand 1 (PD-1/L1)-Exposed Participants (MK-7902-004/E7080-G000-225/LEAP-004) (NCT NCT03776136)

Last Updated: 2024-10-09

Results Overview

ORR was defined as the percentage of participants in the analysis population who have a confirmed Complete Response (CR: disappearance of all lesions) or a Partial Response (PR: ≥30% decrease in the sum of target lesion diameters without progression in other lesions) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR). Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

103 participants

Primary outcome timeframe

Up to approximately 55 months

Results posted on

2024-10-09

Participant Flow

Participant milestones

Participant milestones
Measure	Lenvatinib + Pembrolizumab Participants received lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
Overall Study STARTED	103
Overall Study Treated	103
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	103

Reasons for withdrawal

Reasons for withdrawal
Measure	Lenvatinib + Pembrolizumab Participants received lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
Overall Study Death	85
Overall Study Withdrawal by Subject	3
Overall Study Sponsor Decision	15

Baseline Characteristics

Efficacy and Safety of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) for Advanced Melanoma in Anti-Programmed Death-1/Programmed Death-Ligand 1 (PD-1/L1)-Exposed Participants (MK-7902-004/E7080-G000-225/LEAP-004)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lenvatinib + Pembrolizumab n=103 Participants Participants received lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
Age, Continuous	60.7 Years STANDARD_DEVIATION 13.4 • n=5 Participants
Sex: Female, Male Female	48 Participants n=5 Participants
Sex: Female, Male Male	55 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	100 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	98 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 55 months

Population: All participants who received at least one dose of study intervention.

Outcome measures

Outcome measures
Measure	Lenvatinib + Pembrolizumab n=103 Participants Participants received lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
Objective Response Rate (ORR)	21.4 Percentage of Participants Interval 13.9 to 30.5

SECONDARY outcome

Timeframe: Up to approximately 55 months

Population: All participants who received at least one dose of study intervention.

PFS was defined as the time from first day of study intervention to the first documented progressive disease (PD) per RECIST 1.1 by BICR, or death from any cause, whichever occurred first. Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). PFS was calculated using the nonparametric Kaplan-Meier method; participants who did not experience a PFS event were censored at the last disease assessment, or the last assessment before new anticancer treatment if new treatment was initiated.

Outcome measures

Outcome measures
Measure	Lenvatinib + Pembrolizumab n=103 Participants Participants received lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
Progression-free Survival (PFS)	4.2 Months Interval 3.5 to 6.3

SECONDARY outcome

Timeframe: Up to approximately 55 months

Population: All participants who received at least one dose of study intervention.

OS was defined as the time from the first day of study intervention to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was calculated using the nonparametric Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Lenvatinib + Pembrolizumab n=103 Participants Participants received lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
Overall Survival (OS)	14.0 Months Interval 10.8 to 18.3

SECONDARY outcome

Timeframe: Up to approximately 55 months

Population: All participants who received at least one dose of study intervention, and who experience a confirmed CR or PR.

For participants who demonstrated a confirmed Complete Response (CR: disappearance of all lesions) or Partial Response (PR: ≥30% decrease in the sum of target lesion diameters without progression in other lesions) per RECIST 1.1, DOR was defined as the time from first documented CR or PR until progressive disease (PD) or death from any cause, whichever occurs first. Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). DOR was calculated using the nonparametric Kaplan-Meier method for censored data.

Outcome measures

Outcome measures
Measure	Lenvatinib + Pembrolizumab n=22 Participants Participants received lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
Duration of Response (DOR)	8.5 Months Interval 3.2 to 40.8

SECONDARY outcome

Timeframe: Cycle 1 Day 1: 0.5 to 4 hours and 6 to 10 hours postdose; Cycle 1 Day 15: Predose and 2 to 12 hours postdose; Cycle 2 Day 1: Predose, 0.5 to 4 hours, and 6 to 10 hours post-dose (each cycle =21 days)

Population: All participants who received at least one dose of study intervention, and had data available for AUC0-inf.

AUC0-inf was defined as the area under the concentration-time curve from time zero extrapolated to infinity. Plasma blood samples collected at specified timepoints, were used to estimate AUC0-inf following Lenvatinib and Pembrolizumab administration. Based on the lenvatinib plasma concentration data obtained on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, a protocol specified population PK analysis was performed to characterize the steady state AUC0-inf of lenvatinib when co-administered with pembrolizumab.

Outcome measures

Outcome measures
Measure	Lenvatinib + Pembrolizumab n=103 Participants Participants received lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
Area Under the Concentration Time Curve of Lenvatinib From Time 0 to Infinity (AUC 0-inf)	3005 ng*hr/mL Geometric Coefficient of Variation 39.5

SECONDARY outcome

Timeframe: Up to approximately 55 months

Population: All participants who received at least one dose of study intervention.

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE is presented.

Outcome measures

Outcome measures
Measure	Lenvatinib + Pembrolizumab n=103 Participants Participants received lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
Number of Participants Who Experience At Least One Adverse Event (AE)	102 Participants

SECONDARY outcome

Timeframe: Up to approximately 48 months

Population: All participants who received at least one dose of study intervention.

Outcome measures

Outcome measures
Measure	Lenvatinib + Pembrolizumab n=103 Participants Participants received lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
Number of Participants Who Discontinue Study Treatment Due to an AE	15 Participants

Adverse Events

Lenvatinib + Pembrolizumab

Serious events: 48 serious events

Other events: 101 other events

Deaths: 86 deaths

Serious adverse events

Serious adverse events
Measure	Lenvatinib + Pembrolizumab n=103 participants at risk Participants received lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
Blood and lymphatic system disorders Febrile neutropenia	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Immune thrombocytopenia	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Acute coronary syndrome	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Bradycardia	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Supraventricular tachycardia	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Abdominal pain	1.9% 2/103 • Number of events 2 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Abdominal pain upper	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Colitis	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Diarrhoea	4.9% 5/103 • Number of events 5 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Enteritis	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Intestinal obstruction	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Intra-abdominal haematoma	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Melaena	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Nausea	1.9% 2/103 • Number of events 2 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Oesophagitis	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Pancreatitis	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Proctalgia	0.97% 1/103 • Number of events 2 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Proctitis	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders General physical health deterioration	1.9% 2/103 • Number of events 2 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Malaise	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Non-cardiac chest pain	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Pyrexia	1.9% 2/103 • Number of events 2 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Hepatobiliary disorders Biliary colic	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Hepatobiliary disorders Biliary obstruction	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Hepatobiliary disorders Cholecystitis acute	1.9% 2/103 • Number of events 2 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Hepatobiliary disorders Cholecystitis chronic	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Appendicitis	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Biliary sepsis	0.97% 1/103 • Number of events 2 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Escherichia bacteraemia	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Groin abscess	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Infection	1.9% 2/103 • Number of events 2 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Pelvic abscess	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Pneumonia	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Pneumonia aspiration	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Sepsis	3.9% 4/103 • Number of events 4 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Viral upper respiratory tract infection	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Wound infection	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Injury, poisoning and procedural complications Femoral neck fracture	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Injury, poisoning and procedural complications Muscle rupture	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Injury, poisoning and procedural complications Wound secretion	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Platelet count decreased	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Failure to thrive	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hyperglycaemia	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hyperkalaemia	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hyponatraemia	2.9% 3/103 • Number of events 4 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Malnutrition	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Fistula	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Cerebrovascular accident	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Horner's syndrome	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Syncope	1.9% 2/103 • Number of events 2 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Psychiatric disorders Confusional state	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Psychiatric disorders Disorientation	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Renal and urinary disorders Acute kidney injury	1.9% 2/103 • Number of events 3 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Renal and urinary disorders Renal impairment	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Renal and urinary disorders Urinary retention	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Skin and subcutaneous tissue disorders Skin ulcer	0.97% 1/103 • Number of events 1 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Vascular disorders Hypertension	1.9% 2/103 • Number of events 3 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.

Other adverse events

Other adverse events
Measure	Lenvatinib + Pembrolizumab n=103 participants at risk Participants received lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
Blood and lymphatic system disorders Anaemia	13.6% 14/103 • Number of events 15 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Neutropenia	6.8% 7/103 • Number of events 9 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Hypothyroidism	35.9% 37/103 • Number of events 39 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Abdominal pain	18.4% 19/103 • Number of events 27 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Abdominal pain upper	8.7% 9/103 • Number of events 13 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Constipation	31.1% 32/103 • Number of events 39 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Diarrhoea	48.5% 50/103 • Number of events 123 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Dry mouth	14.6% 15/103 • Number of events 18 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Gastrooesophageal reflux disease	11.7% 12/103 • Number of events 13 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Nausea	44.7% 46/103 • Number of events 64 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Stomatitis	13.6% 14/103 • Number of events 15 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Toothache	5.8% 6/103 • Number of events 6 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Vomiting	27.2% 28/103 • Number of events 51 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Asthenia	30.1% 31/103 • Number of events 59 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Fatigue	35.0% 36/103 • Number of events 44 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Mucosal inflammation	17.5% 18/103 • Number of events 30 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Oedema peripheral	5.8% 6/103 • Number of events 6 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Pyrexia	19.4% 20/103 • Number of events 23 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Upper respiratory tract infection	5.8% 6/103 • Number of events 6 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Urinary tract infection	14.6% 15/103 • Number of events 17 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Alanine aminotransferase increased	15.5% 16/103 • Number of events 19 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Amylase increased	9.7% 10/103 • Number of events 15 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Aspartate aminotransferase increased	12.6% 13/103 • Number of events 18 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Blood alkaline phosphatase increased	6.8% 7/103 • Number of events 9 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Blood magnesium decreased	5.8% 6/103 • Number of events 18 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Blood thyroid stimulating hormone increased	8.7% 9/103 • Number of events 12 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Haemoglobin decreased	6.8% 7/103 • Number of events 10 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Lipase increased	13.6% 14/103 • Number of events 14 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Neutrophil count decreased	5.8% 6/103 • Number of events 6 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Weight decreased	22.3% 23/103 • Number of events 25 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Decreased appetite	40.8% 42/103 • Number of events 58 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hypokalaemia	9.7% 10/103 • Number of events 15 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hypomagnesaemia	12.6% 13/103 • Number of events 23 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hyponatraemia	8.7% 9/103 • Number of events 9 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hypophosphataemia	5.8% 6/103 • Number of events 7 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Arthralgia	26.2% 27/103 • Number of events 39 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Back pain	19.4% 20/103 • Number of events 24 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Muscular weakness	5.8% 6/103 • Number of events 6 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Myalgia	14.6% 15/103 • Number of events 18 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Pain in extremity	10.7% 11/103 • Number of events 12 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Dizziness	17.5% 18/103 • Number of events 22 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Dysgeusia	11.7% 12/103 • Number of events 15 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Headache	28.2% 29/103 • Number of events 56 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Psychiatric disorders Insomnia	10.7% 11/103 • Number of events 12 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Renal and urinary disorders Proteinuria	22.3% 23/103 • Number of events 34 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Aphonia	6.8% 7/103 • Number of events 10 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Cough	11.7% 12/103 • Number of events 14 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Dysphonia	21.4% 22/103 • Number of events 24 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.8% 8/103 • Number of events 8 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.8% 6/103 • Number of events 8 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.7% 9/103 • Number of events 9 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Skin and subcutaneous tissue disorders Dry skin	10.7% 11/103 • Number of events 11 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	6.8% 7/103 • Number of events 8 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Skin and subcutaneous tissue disorders Pruritus	17.5% 18/103 • Number of events 19 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Skin and subcutaneous tissue disorders Rash	11.7% 12/103 • Number of events 15 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Skin and subcutaneous tissue disorders Vitiligo	5.8% 6/103 • Number of events 6 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Vascular disorders Hypertension	56.3% 58/103 • Number of events 88 • Up to approximately 55 months All-cause mortality and adverse events (AE): all participants who received ≥1 dose of treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
Publication restrictions are in place

Restriction type: OTHER