Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Lung Neoplasms

Melanoma

Carcinoma, Renal Cell

Carcinoma, Transitional Cell

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Lenvatinib

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants with selected tumors will receive oral lenvatinib at a starting dose of 20 milligrams (mg) once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks (Q3W) on a 21-day treatment cycle until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.

lenvatinib

pembrolizumab

This is an open-label Phase 1b study designed to confirm the tolerability and safety of lenvatinib in combination with pembrolizumab in participants with selected solid tumors (non-small cell lung cancer, predominantly clear cell renal cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, or melanoma \[excluding uveal melanoma\]).

Phase 1b Trial of Lenvatinib Plus Pembrolizumab in Participants With Selected Solid Tumors

An Open-Label Phase 1b Trial of Lenvatinib Plus Pembrolizumab in Subjects With Selected Solid Tumors

A TEAE was defined as an adverse event (AE) that emerged during the time from the first dose of study drug to 30 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. A Serious AE is any untoward medical occurrence that at any dose: resulted in death; was life threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death) required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria.

A DLT is defined as any of the following: any of the hematological or nonhematological toxicities specified in the protocol that are considered to be at least possibly related to lenvatinib and/or pembrolizumab occurring during Cycle 1; failed to administer greater than or equal to 75 percent (%) of the planned dosage of lenvatinib as a result of treatment-related toxicity during Cycle 1; participants who discontinued due to treatment-related toxicity in Cycle 1; greater than a 2-week delay in starting pembrolizumab in Cycle 2 because of a treatment-related toxicity, even if the toxicity does not meet DLT criteria.

ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) for target and non-target lesions. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 millimeter (mm). 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. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ.

DOR was defined as time from the first documented of CR or PR to the date of first documentation of disease progression (PD) (based on modified RECIST 1.1) or death (whichever occurs first). CR was defined as the disappearance of all target lesions and non-target lesions. 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. PD for target lesion, was defined as a minimum 20% increase and a minimum 5 mm absolute increase in sum of diameters compared to nadir, or PD for non-target lesion(s) or unequivocal new lesion(s). Nadir was defined as lowest measure sum of diameters of target lesions at any time point from baseline onward. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ. DOR = Date of PD/death (whichever occurs first) - Date of first CR or PR + 1.

Rac (Cmax) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Rac (Cmax) = Css,max on Cycle 1 Day 15 / Cmax on Cycle 1 Day 1

Rac (AUC) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Rac (AUC) = AUC(0-t) on Cycle 1 Day 15 / AUC(0-t) on Cycle 1 Day 1.

The peak trough fluctuation within complete dosing interval at steady state, calculated as PTF (%) = (\[Cmax - Cmin\]/Cav ) multiplied by 100

Merck Sharp & Dohme LLC

Eisai Co., Ltd.

Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).

Lenvatinib 20 mg Plus Pembrolizumab 200 mg

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The safety analysis set included all participants who received at least 1 dose of study drug.

Inquiry Service

TEAEs

SAEs

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

The DLT set included all participants who completed Cycle 1 without major protocol deviation with at least 75% of study drug compliance and were assessed for DLT, and participants who experienced DLT during Cycle 1.

Number of Participants With Dose-limiting Toxicities

The efficacy analysis set included all participants who received at least 1 dose of study drug.

Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

The efficacy analysis set included all participants who received at least 1 dose of study drug. Here overall number analyzed "N" included the participants who had CR or PR.

Duration of Response (DOR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.

Cmax: Maximum Plasma Concentration of Lenvatinib in Combination With Pembrolizumab

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Lenvatinib in Combination With Pembrolizumab

Cycle 1 Day 1

Cycle 1 Day 15

The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed "N" included the participants who were evaluable for the outcome measure.

T1/2: Terminal Half-life of Lenvatinib in Combination With Pembrolizumab

AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Lenvatinib in Combination With Pembrolizumab

AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Lenvatinib in Combination With Pembrolizumab

Vz/F: Apparent Volume of Distribution at Terminal Phase of Lenvatinib in Combination With Pembrolizumab

The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here, overall number analyzed "N" are the participants who were evaluable for the outcome measure.

CL/F: Apparent Total Clearance Following Oral Dosing of Lenvatinib in Combination With Pembrolizumab

MRT: Mean Residence Time of Lenvatinib in Combination With Pembrolizumab

Css,Max: Maximum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab

Css,Min: Minimum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab

Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Lenvatinib in Combination With Pembrolizumab

AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Lenvatinib in Combination With Pembrolizumab

Clss/F: Apparent Total Clearance Following Oral Administration at Steady State of Lenvatinib in Combination With Pembrolizumab

Css,Av: Average Steady State Plasma Concentration of Lenvatinib in Combination With Pembrolizumab

Rac (Cmax): Accumulation Index of Cmax for Lenvatinib in Combination With Pembrolizumab

Rac (AUC): Accumulation Index of AUC for Lenvatinib in Combination With Pembrolizumab

Lambda z: Terminal Phase Elimination Rate Constant of Lenvatinib in Combination With Pembrolizumab

PTF: Peak-trough Fluctuation Ratio of Lenvatinib in Combination With Pembrolizumab

Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status for Pembrolizumab

Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 milligram (mg), capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing Dose limiting toxicities (DLTs). In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).

Spots Global Cancer Trial Database for Phase 1b Trial of Lenvatinib Plus Pembrolizumab in Participants With Selected Solid Tumors

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Study Description

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