Pembrolizumab and Lenvatinib in Patients With Brain Metastases From Melanoma or Renal Cell Carcinoma

NCT04955743 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 2000030391
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2, Simon's 2-stage designed study with 2 cohorts of anti-PD-1/PD-L1 experienced patients with untreated brain metastases: 1) melanoma and 2) renal cell carcinoma (RCC).

Conditions

Melanoma; Renal Cell Carcinoma; Brain Metastases; PD1/PD-L1 Experienced; Pembrolizumab; Lenvatinib; Metastatic Melanoma

Outcome Measures

Primary Outcomes (1)

• Best brain metastasis response rate (BMRR)

  Best brain metastasis response rate (BMRR), defined as PR and CR per modified RECIST 1.1.

  up to 2 years from the start of treatment

Secondary Outcomes (4)

• Best overall objective response rate

  up to 2 years from the start of treatment

• Progression Free Survival (PFS)

  up to 2 years from the start of treatment or to time of disease progression

• Overall Survival (OS)

  up to 2 years from the start of treatment or to time of death

• Duration of brain metastasis response

  up to 2 years from the start of treatment

Study Arms (2)

Cohort 1: Melanoma

EXPERIMENTAL

Participants who are melanoma (PD-1/PD-L1-experienced)

Drug: Pembrolizumab; Drug: Lenvatinib

Cohort 2: Renal Cell Carcinoma

EXPERIMENTAL

Participants who are Renal Cell Carcinoma (PD-1/PD-L1 experienced).

Drug: Pembrolizumab; Drug: Lenvatinib

Interventions

Pembrolizumab DRUG

200 mg intravenous (IV) is administered every 3 weeks

Cohort 1: Melanoma; Cohort 2: Renal Cell Carcinoma

Lenvatinib DRUG

20 mg orally (PO) is administered daily

Cohort 1: Melanoma; Cohort 2: Renal Cell Carcinoma

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of melanoma or RCC and untreated metastatic brain disease will be enrolled in this study.
• Male participants: A male participant must agree to use a contraception as detailed in the protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance per protocol during the treatment period and for at least 120 days after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have histologic or cytologic confirmation from any body site of metastatic melanoma irrespective of BRAF mutation status or renal cell carcinoma irrespective of histologic subtype.
• Patients who have had prior resection or biopsy of a CNS and/or extracranial metastasis will be required to provide a formalin-fixed, paraffin embedded (FFPE) specimen from tumor taken at the time of surgery, if available. Fresh biopsies of a metastatic lesion should be performed if clinically able.
• Note: Participants are not required to have new or repeat brain metastasis biopsies for enrollment on the trial.
• Note: For those who have never had CNS brain metastasis biopsies, tissue of an accessible extracranial lesion will be obtained pre-treatment, unless deemed not possible by the treating physician and upon discussion with PI. In this case, archival extracranial metastatic tissue will be suitable.
• Have at least one brain metastasis that is at least 5 mm AND twice the MRI slice thickness, but less than or equal to 3 cm, which is asymptomatic, has not been previously radiated, and is not requiring immediate local therapy or steroids. Lesions situated in a previously irradiated area are considered allowed if measurable per the aforementioned criteria and if progression has been demonstrated. Patients with any lesion(s) \>3 cm can be enrolled provided the following: (1) the lesion must receive local treatment prior to initiation of study drugs (either by stereotactic radiosurgery or resection), (2) the patient is not symptomatic from the lesion(s) once local therapy has been administered, and (3) at least one additional, non-treated lesion between 5 mm and 3 cm is still present.
• Prior treatment for either the Melanoma or RCC cohorts may include: Patients must have received at least 2 doses of an anti-PD-1/PD-L1 drug at some point in their treatment course. Any number of prior treatments including PD-1/PD-L1 inhibitors are allowed. Anti-PD-1/PD-L1 does not have to be the most recent therapy. Patients with melanoma who developed brain metastasis within 6 months of the last dose of adjuvant anti-PD-1 can be enrolled.
• Life expectancy of at least 3 months.
• A history of radiotherapy for brain metastases is allowed up to 1 week before study treatment provided that neurologic sequelae are resolved, and that measurable untreated target lesion(s) remain.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation.

You may not qualify if:

• Symptomatic melanoma or RCC brain metastases at the time of therapy initiation.
• Active use of corticosteroids to control CNS symptoms, unless steroid requirement has been decreasing and currently on ≤10 mg of prednisone or its equivalent without CNS symptoms for 7 days or more.
• Overt hemorrhage from CNS metastases.
• Presence of leptomeningeal disease.
• Unable to undergo MRI imaging (either due to such conditions as inability to lie flat for the scan duration, incompatible medical devices at risk for malfunction, and foreign metal objects that pose a safety risk for imaging).
• A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received anti-cancer therapy including investigational agents within 14 days prior to allocation or less than 4 weeks from prior immunomodulating antibody (excluding anti-PD1/PD-L1).
• Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy, rash, and/or alopecia may be eligible.
• Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received prior CNS radiotherapy within 1 week of start of study treatment. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or is requiring active treatment.

Sponsors & Collaborators

• Yale University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06517-3534, United States

Location

MeSH Terms

Conditions

Melanoma; Carcinoma, Renal Cell; Brain Neoplasms

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Harriet Kluger, MD

  Professor of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: None (Open Label)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 28, 2021
• First Posted: July 9, 2021
• Study Start: February 9, 2022
• Primary Completion: May 28, 2025
• Study Completion: May 28, 2025
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)