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

NCT03006887 | Completed Phase 1 Results

• 2 other identifiers: E7080-J081-115KEYNOTE 523
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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 \[excluding uveal melanoma\]).

Conditions

Solid Tumors

Keywords

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; non-uveal melanoma; E7080; lenvatinib; pembrolizumab; Japan

Outcome Measures

Primary Outcomes (2)

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

  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

  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 Outcomes (21)

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

  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

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

  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

  Cycle 1 Day 1: 0-24 hours

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

  Cycle 1 Day 1: 0-24 hours

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

  Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours

Study Arms (1)

lenvatinib 20 mg plus pembrolizumab 200 mg

EXPERIMENTAL

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; Drug: pembrolizumab

Interventions

lenvatinib DRUG

lenvatinib capsules

lenvatinib 20 mg plus pembrolizumab 200 mg

pembrolizumab DRUG

pembrolizumab intravenous infusion

lenvatinib 20 mg plus pembrolizumab 200 mg

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eisai Co., Ltd.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Eisai Trial Site 1

Chuo-ku, Tokyo, Japan

Location

Related Publications (1)

• Kitano S, Fujiwara Y, Shimizu T, Iwasa S, Yonemori K, Kondo S, Shimomura A, Koyama T, Ebata T, Ikezawa H, Hayata N, Minoshima Y, Miura T, Kubota T, Yamamoto N. A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2022 Dec;90(6):523-529. doi: 10.1007/s00280-022-04480-w. Epub 2022 Oct 26.

  PMID: 36289094 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Endometrial Neoplasms; Carcinoma, Transitional Cell; Squamous Cell Carcinoma of Head and Neck

Interventions

lenvatinib; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma, Squamous Cell; Head and Neck Neoplasms

Results Point of Contact

• Title: Inquiry Service
• Organization: Eisai, Inc.

eisai-chiken_hotline@hhc.eisai.co.jp

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2016
• First Posted: December 30, 2016
• Study Start: January 12, 2017
• Primary Completion: April 15, 2020
• Study Completion: April 15, 2020
• Last Updated: May 20, 2021
• Results First Posted: May 20, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)