relatlimab (BMS-986016)

P2, N=266, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Apr 2025 --> Oct 2025

P1, N=32, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2025 --> Aug 2027 | Trial primary completion date: Mar 2025 --> Mar 2027

Nivolumab and relatlimab combination therapy can modulate the tumor microenvironment in patients with both IO-refractory and IO-naïve melanoma. Further research is needed to identify patients who will most benefit from anti-LAG-3/PD-(L)1 agents, and to elucidate the mechanisms of action of, and resistance to, this combination therapy in patients with advanced melanoma.

This study is the first cohort analysis of hypophysitis in patients treated with relatlimab-nivolumab compared to nivolumab monotherapy. Combination treatment with relatlimab-nivolumab confers a significantly higher risk of developing adrenal insufficiency, likely secondary to hypophysitis, compared to nivolumab alone.

P1, N=35, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | Trial completion date: Jul 2025 --> Jul 2024

P1/2, N=14, Terminated, Multiple Myeloma Research Consortium | Trial completion date: Dec 2024 --> Aug 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2023 --> Aug 2024; Pharmaceutical support has been discontinued.

P1/2, N=162, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting

P2, N=92, Not yet recruiting, Duke University

We found that the novel tri-specific tribodies activated human peripheral blood mononuclear cells more efficiently than clinically validated mAbs (atezolizumab, pembrolizumab, and relatlimab) either used alone or in combination with 53 P, leading to a stronger tumor cytotoxicity and cytokines release. We shed light on the molecular basis of this potentiated anti-tumor activity by evidencing that the insertion of the anti-PD-L1 moiety in 53L10 led not only to stronger binding of the tri-specific to tumor cells but also efficiently blocked the effects of increased PD-L1 on tumor cells, induced by IFNγ secretion also due to T-cell activation. These results are important also for the design of novel T-cell engagers targeting other tumor antigens.

P2, N=59, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed | Trial completion date: Feb 2025 --> Sep 2024

P3, N=360, Recruiting, Immatics US, Inc. | Not yet recruiting --> Recruiting

No abstract available

While ORR did not meet prespecified expansion criteria in any treatment arm, the safety profile of the combinations was manageable. FRACTION-GC represents a novel adaptive protocol for testing multiple combination immunotherapies.

P2, N=20, Recruiting, Melanoma Institute Australia | Not yet recruiting --> Recruiting

The nivolumab/relatlimab combination is licensed only for PDL-1-negative melanoma and reimbursed in seven countries of Europe. Tebentafusp is reimbursed in 15 countries and talimogene laherpervec in 5. In 2024, adjuvant treatments for stage III melanoma are reimbursed in 22 countries for dabrafenib/trametinib and 24 of 27 for anti-PD1 antibodies. Pembrolizumab and nivolumab are reimbursed in 15 and 8 countries, respectively, for stage IIB/IIC disease.While there have been improvements in the reimbursement of metastatic melanoma treatments in Europe, challenges and discrepancies remain. Further efforts at European and global levels are needed to harmonize and enhance access to cancer medicines.

P2, N=468, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Sep 2025 --> Jan 2026

P2, N=266, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Dec 2024 --> Apr 2025

P3, N=360, Not yet recruiting, Immatics US, Inc.

P2, N=90, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Mar 2027 --> Jul 2027 | Trial primary completion date: Mar 2027 --> Jul 2027

P2, N=80, Recruiting, Dan Zandberg | Trial completion date: Sep 2027 --> Sep 2026 | Trial primary completion date: May 2027 --> May 2026

P1/2, N=21, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Apr 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P3, N=680, Recruiting, Immunocore Ltd | Trial primary completion date: Dec 2026 --> Oct 2027

Results showed antitumour activity and manageable safety with NIVO + RELA. Findings also support NIVO + IPI as an effective combination regimen in IO-naive patients with aRCC.

P2, N=30, Not yet recruiting, University of California, San Diego | Initiation date: Oct 2024 --> Jan 2025

P2, N=27, Active, not recruiting, Jose Lutzky, MD | Trial completion date: Dec 2026 --> Jan 2026 | Trial primary completion date: Dec 2024 --> Jan 2024

P2, N=385, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed

These monoclonal antibodies target immune checkpoints, including cytotoxic T-lymphocyte-associated protein 4 (ipilimumab and tremelimumab), programmed death 1 (nivolumab, pembrolizumab, cemiplimab, and dostarlimab), programmed death ligand 1 (atezolizumab, avelumab, and durvalumab), and lymphocyte activation gene 3 (relatlimab), and effectively augment the immune response against tumor cells. Despite clinical improvements with immunomodulatory therapy, with corticosteroids the mainstay of treatment, mortality remains high, particularly in those with associated myocarditis or respiratory failure requiring intubation, where mortality occurs in up to 50%. ICI withdrawal can lead to cancer progression and death, highlighting a need for improved approaches to ICI rechallenge, performed in limited patients with variable success to date.

P1/2, N=162, Recruiting, Bristol-Myers Squibb | Trial primary completion date: Jun 2024 --> Oct 2025

P2, N=90, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Phase classification: P1 --> P2

P1/2, N=30, Not yet recruiting, M.D. Anderson Cancer Center

P1, N=33, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting

P2/3, N=135, Not yet recruiting, Linnaeus Therapeutics, Inc. | Phase classification: P3 --> P2/3

Immune checkpoint inhibitors (ICIs) have shown great success, with FDA-approved drugs like PD-1 inhibitors (Nivolumab, Pembrolizumab, Cemiplimab), PD-L1 inhibitors (Atezolizumab, Durvalumab, Avelumab), and CTLA-4 inhibitors (Ipilimumab, Tremelimumab), alongside LAG-3 inhibitor Relatlimab. This review aims to fill this gap by providing an analysis of the current clinical status of ICIs, emerging biomarkers, mechanisms of resistance, strategies to enhance therapeutic efficacy, and assessment of adverse effects. This review is crucial to furthering our understanding of ICIs and optimizing their application in cancer therapy.

P2, N=42, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

Currently, with the approval of relatlimab, a LAG-3 blocking antibody, a third player, has been used in the fight against cancer...However, the complex biology of LAG-3 may hinder its full development as a therapeutic alternative. In this review, we provide in-depth insight into the biology of LAG-3 and its current and future development in cancer treatment.

P2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P2, N=30, Not yet recruiting, University of California, San Diego

P3, N=135, Not yet recruiting, Linnaeus Therapeutics, Inc.

P2, N=42, Completed, John Kirkwood | Active, not recruiting --> Completed | Trial completion date: Jul 2027 --> Jul 2024 | Trial primary completion date: Jul 2027 --> Jul 2024

Our retrospective review at a tertiary cancer center of patients with stage 3 and 4 melanoma treated with NIVO-RELA revealed an overall response rate (ORR) of 39%, with notable improvements in median PFS and ORR, especially in first-line treated patients. Our study highlights the superior efficacy of NIVO-RELA over previous reports, demonstrating its significant potential in the treatment landscape of advanced melanoma.

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

P1, N=32, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Feb 2025 --> Aug 2025 | Trial primary completion date: Sep 2024 --> Mar 2025