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

May 19, 2021 updated by: Eisai Co., Ltd.

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

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]).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Tokyo
      • Chuo-ku, Tokyo, Japan
        • EISAI Trial Site 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically and/or cytologically confirmed selected solid tumor types that have progressed after treatment with standard therapies or for which there are no other appropriate therapies available.

The selected tumor types are: 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)

  • At least 1 measurable target lesion according to modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
  • Participants must have an Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) of 0 to 1.
  • Adequate liver function as evidenced by bilirubin ≤1.5×ULN and alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3×ULN (in the case of liver metastases ≤5×ULN). In case ALP is >3×ULN (in the absence of liver metastases) or >5×ULN (in the presence of liver metastases) AND the participant also is known to have bone metastases, the liver-specific ALP must be separated from the total and used to assess the liver function instead of the total ALP.
  • Males or females age ≥20 years at the time of informed consent
  • Life expectancy of 12 weeks or more
  • Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol

Exclusion Criteria:

  • Prior anticancer treatment within 28 days (or 5 times the half-life time, whichever is shorter) or any investigational agent within 28 days prior to the first dose of study drugs. All toxicities related to prior treatments must be resolved to Grade ≤1 (except alopecia).
  • Prior treatment with lenvatinib or any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, excluding cancer types such as melanoma and non-small cell lung cancer where prior treatment with one anti-PD-1, anti-PD-L1, or anti-PD-L2 agent is allowed
  • Participants must have recovered adequately from any complications from major surgery prior to starting therapy.
  • New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months
  • Prolongation of QTc (Fridericia formula) interval to >480 milliseconds (ms)
  • Active infection (any infection requiring systemic treatment)
  • Participant is known to be positive for Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C
  • Known intolerance to either of the study drugs (or any of the excipients)
  • History of organ allograft
  • Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis, or has a history of interstitial lung disease
  • Females who are breastfeeding or pregnant at Screening or Baseline.
  • Females of childbearing potential.
  • Participants must be on a stable dose of the same oral hormonal contraceptive product for at least 4 weeks before dosing with study drug and for the duration of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: lenvatinib 20 mg plus pembrolizumab 200 mg
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.
Drug: lenvatinib
lenvatinib capsules
Drug: pembrolizumab
pembrolizumab intravenous infusion

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: From the first dose until 30 days after the last dose (approximately 2 years 7 months)
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.
From the first dose until 30 days after the last dose (approximately 2 years 7 months)
Number of Participants With Dose-limiting Toxicities
Time Frame: Cycle 1 (Cycle length=21 days)
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.
Cycle 1 (Cycle length=21 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
Time Frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 7 months
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.
From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 7 months
Duration of Response (DOR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
Time Frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 7 months.
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.
From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 7 months.
Cmax: Maximum Plasma Concentration of Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 1: 0-24 hours
Cycle 1 Day 1: 0-24 hours
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 1: 0-24 hours
Cycle 1 Day 1: 0-24 hours
T1/2: Terminal Half-life of Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
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
Time Frame: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 1: 0-24 hours
Cycle 1 Day 1: 0-24 hours
Vz/F: Apparent Volume of Distribution at Terminal Phase of Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
CL/F: Apparent Total Clearance Following Oral Dosing of Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 1: 0-24 hours
Cycle 1 Day 1: 0-24 hours
MRT: Mean Residence Time of Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
Css,Max: Maximum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 15: 0-24 hours
Cycle 1 Day 15: 0-24 hours
Css,Min: Minimum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 15: 0-24 hours
Cycle 1 Day 15: 0-24 hours
Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 15: 0-24 hours
Cycle 1 Day 15: 0-24 hours
AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 15: 0-24 hours
Cycle 1 Day 15: 0-24 hours
Clss/F: Apparent Total Clearance Following Oral Administration at Steady State of Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 15: 0-24 hours
Cycle 1 Day 15: 0-24 hours
Css,Av: Average Steady State Plasma Concentration of Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 15: 0-24 hours
Cycle 1 Day 15: 0-24 hours
Rac (Cmax): Accumulation Index of Cmax for Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours
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
Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours
Rac (AUC): Accumulation Index of AUC for Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours
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.
Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours
Lambda z: Terminal Phase Elimination Rate Constant of Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
PTF: Peak-trough Fluctuation Ratio of Lenvatinib in Combination With Pembrolizumab
Time Frame: Cycle 1 Day 15: 0-24 hours
The peak trough fluctuation within complete dosing interval at steady state, calculated as PTF (%) = ([Cmax - Cmin]/Cav ) multiplied by 100
Cycle 1 Day 15: 0-24 hours
Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status for Pembrolizumab
Time Frame: Day 1 of Cycles 1, 2, 4, 6, and 8 and every 4 cycles thereafter; within 30 days after discontinuation or until the initiation of other anticancer treatment, whichever is earlier (Cycle length=21 days); up to 31 months
Day 1 of Cycles 1, 2, 4, 6, and 8 and every 4 cycles thereafter; within 30 days after discontinuation or until the initiation of other anticancer treatment, whichever is earlier (Cycle length=21 days); up to 31 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eisai Co., Ltd.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 12, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 15, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 15, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 27, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 29, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 30, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 20, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 19, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • E7080-J081-115
  • KEYNOTE 523 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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