Lenvatinib Plus Pembrolizumab In Patients With Immune Checkpoint Inhibitor Naïve Metastatic Uveal Melanoma

NCT05308901 | Active Not Recruiting Phase 2 Results FDA Drug

• 1 other identifier: 2021000802
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy of lenvatinib and pembrolizumab to treat metastatic uveal melanoma.

Conditions

Melanoma, Uveal

Keywords

Melanoma; Uveal; Pembrolizumab; Phase 2; Lenvatinib

Outcome Measures

Primary Outcomes (1)

• Evaluate the Effect of Lenvatinib Plus Pembrolizumab on Progression Free Survival

  Progression free survival, defined as the time from enrollment to the first documented evidence of disease progression or death.

  An average of 6 months and 7 days from the time of enrollment.

Secondary Outcomes (3)

• Evaluate the Objective Response Rate Resulting From Treatment With Lenvatinib Plus Pembrolizumab

  6 weeks after treatment discontinuation

• Evaluate the Effect of Treatment With Lenvatinib Plus Pembrolizumab on Overall Survival

  12 weeks post treatment discontinuation

• Evaluate the Safety and Tolerability of Treatment With Lenvatinib Plus Pembrolizumab in Patients With Metastatic Uveal Melanoma

  30 days after last treatment dose, on average 5 months from the start of treatment.

Study Arms (1)

Pembrolizumab + Lenvatinib

EXPERIMENTAL

Lenvatinib 20 mg daily plus pembrolizumab 200 mg IV every 3 weeks.

Drug: Pembrolizumab; Drug: Lenvatinib

Interventions

Pembrolizumab DRUG

200 mg IV every 3 weeks for a maximum of 2 years.

Also known as: Keytruda

Pembrolizumab + Lenvatinib

Lenvatinib DRUG

20 mg daily for a maximum of 2 years.

Pembrolizumab + Lenvatinib

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 metastatic uveal melanoma will be enrolled in this study.
• Male participants must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose of Lenvatinib and refrain from donating sperm during this period.
• Female participants are eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days post pembrolizumab or post Lenvatinib whichever occurs last.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have measurable disease based on iRECIST. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. If slides are only available, ten slides would be required. Newly obtained biopsies are preferred to archived tissue.
• 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 first dose of study intervention.
• Have adequate organ function as defined in the following table (Table 2). Specimens must be collected within 7 days prior to the start of study intervention.
• Subjects must agree to undergo paired fresh tumor biopsy specimens (to be collected pre-treatment and day #15). Subjects with tumor metastases that are not amenable to image guided biopsies or who have a contraindication to biopsy (including but not limited to anticoagulation therapy that cannot be interrupted for a biopsy) are still eligible for participation in the clinical trial without undergoing biopsies.

You may not qualify if:

• A WOCBP who has a positive serum pregnancy test within 24 hours prior to the first dose of study intervention (see Appendix 3).
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137). Prior therapy with Tebentafusp is permitted. Prior liver directed therapy is permitted (including but not limited to radioembolization, chemoembolization, immunoembolization, radio-frequency ablation, external beam radiation and resection).
• Participants previously treated with radiation therapy must have recovered from all radiation-related toxicities and not require corticosteroids.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed-virus vaccines and mRNA vaccines are allowed.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing 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 has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, early stage bladder cancer, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
• Has had an allogenic tissue/solid organ transplant.

Sponsors & Collaborators

• Providence Health & Services: lead
• Merck Sharp & Dohme LLC: collaborator
• Eisai Inc.: collaborator

Study Sites (1)

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

MeSH Terms

Conditions

Uveal Melanoma; Melanoma

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; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Dr. Matthew Taylor
• Organization: Providence Portland Medical Center

canrsrchstudies@providence.org

503-215-1979

Study Officials

• Matthew Taylor, MD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: April 4, 2022
• Study Start: August 2, 2022
• Primary Completion: December 3, 2024
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 25, 2025
• Results First Posted: July 25, 2025

Record last verified: 2025-07

Locations

US (1)