1126P - A phase II study of nivolumab/relatlimab in metastatic uveal melanoma

Background

Metastatic uveal melanoma (UM) is a difficult to treat rare malignancy. Lymphocyte activation gene 3(LAG-3) is an immune checkpoint receptor associated with T cell exhaustion highly expressed in uveal melanoma CD8+ T cells (Durante et al.). Relatlimab is a human LAG-3 specific blocking antibody currently approved in combination with PD-1 blocking antibody nivolumab in metastatic cutaneous melanoma. Here we report the results of a phase 2 study in patients with metastatic uveal melanoma (MUM).

Methods

A Simon two-stage minimax design was used. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), median duration of response (mDOR), and safety (AEs). The null hypothesis (ORR=5%) is rejected if 4 or more responses are observed in 27 patients.

Results

As of 1/31/2024, 27 patients were enrolled and treated. No prior PD-1, CTLA-4 and/or LAG-3 blocking antibody treatment was allowed. Patients were treated with nivolumab 480 mg/relatlimab 160 mg IV q4wks to progression or intolerable toxicity. At a median follow -up of 11.2 months, the ORR in the 26 evaluable patients was 7.7% (2/26).) SD and PD were 42.3% (6/18) and 50% (10/18) respectively. 92.6% of patients experienced treatment related adverse events (TRAE). Of 173 TRAE, 88.9%,66.7% and 25.9% were grade 1, 2 and 3, respectively. There were no grade 4/5 AEs. The most common TRAEs were fatigue (55.6%), ALT elevation (40.7%), AST elevation (29.6%) arthralgias (25.9%) and hypothyroidism (25.9%). There were 10 grade 3 TRAE in 7 patients. Six serious adverse reactions (SAE) were seen in 3 patients; one was considered treatment related and 5 were due to PD. Additional results of secondary outcomes will be presented. Results of extensive correlative studies will be submitted as a separate abstract.

Conclusions

Nivolumab + relatlimab is safe but is associated with a low response rate in MUM.

Clinical trial identification

NCT04552223.

Editorial acknowledgement

Legal entity responsible for the study

University of Miami.

Funding

Bristol Myers Squibb.

Disclosure

J. Lutzky: Financial Interests, Personal, Other, reviewed grant applications for department of defense: general dynamics; Financial Interests, Personal, Advisory Board: Regeneron, Immunocore; Financial Interests, Personal, Other, safety monitoring committee: agenus, Celldex; Financial Interests, Institutional, Research Grant, Funding for institutional trial: BMS; Financial Interests, Institutional, Local PI: Trisalus, Takeda, Vyriad, Tango, Immunocore, Replimune, Oncohost, Dragonfly, Iovance, Ideaya. L. Hernandez-Aya: Financial Interests, Personal, Advisory Board: replimune; Financial Interests, Institutional, Local PI: BMS, Immatics, AsherBio, Immunocore; Financial Interests, Institutional, Local PI, Local PI: Replimune. Z. Correa: Financial Interests, Personal and Institutional, Local PI, Local PI for clinical trials: Castle Biosciences, Inc; Financial Interests, Personal and Institutional, Local PI, upcoming COMPASS trial: Aura Biosciences, Inc; Financial Interests, Personal and Institutional, Local PI, local PI for the Darovasertib for uveal melanoma and Co-PI for the metastatic Daro + Crizotnib for metastatic uveal melanoma: Ideaya Biosciences, Inc. J.W. Harbour: Financial Interests, Personal, Advisory Board: Castle Biosciences, Aura Biosciences, IDEAYA Biosciences; Financial Interests, Personal, Royalties: Washington University in St. Louis; Financial Interests, Personal and Institutional, Local PI: IDEAYA Biosciences, Aura Biosciences; Non-Financial Interests, Leadership Role: Collaborative Ocular Oncology Group. All other authors have declared no conflicts of interest.