Clinical trial NCT03006887: Phase 1b Trial of Lenvatinib Plus Pembrolizumab in Participants With Selected Solid Tumors
Official title: An Open-Label Phase 1b Trial of Lenvatinib Plus Pembrolizumab in Subjects With Selected Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-12-30
Enrollment: 6
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 \[excluding uveal melanoma\]).


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From the first dose until 30 days after the last dose (approximately 2 years 7 months)
measure: Number of Participants With Dose-limiting Toxicities
timeFrame: Cycle 1 (Cycle length=21 days)
Secondary outcomes:
measure: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
timeFrame: 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
measure: Duration of Response (DOR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
timeFrame: 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.
measure: Cmax: Maximum Plasma Concentration of Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 1: 0-24 hours
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 1: 0-24 hours
measure: T1/2: Terminal Half-life of Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
measure: 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
timeFrame: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
measure: AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 1: 0-24 hours
measure: Vz/F: Apparent Volume of Distribution at Terminal Phase of Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
measure: CL/F: Apparent Total Clearance Following Oral Dosing of Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 1: 0-24 hours
measure: MRT: Mean Residence Time of Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
measure: Css,Max: Maximum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 15: 0-24 hours
measure: Css,Min: Minimum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 15: 0-24 hours
measure: Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 15: 0-24 hours
measure: AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 15: 0-24 hours
measure: Clss/F: Apparent Total Clearance Following Oral Administration at Steady State of Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 15: 0-24 hours
measure: Css,Av: Average Steady State Plasma Concentration of Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 15: 0-24 hours
measure: Rac (Cmax): Accumulation Index of Cmax for Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours
measure: Rac (AUC): Accumulation Index of AUC for Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours
measure: Lambda z: Terminal Phase Elimination Rate Constant of Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
measure: PTF: Peak-trough Fluctuation Ratio of Lenvatinib in Combination With Pembrolizumab
timeFrame: Cycle 1 Day 15: 0-24 hours
measure: Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status for Pembrolizumab
timeFrame: 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
Other outcomes:
Locations:
city: Chuo-ku
country: Japan
facility: Eisai Trial Site 1
state: Tokyo
Study officials:
References:
citation: 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.