Opdualag (nivolumab/relatlimab-rmbw)

P1/2, N=140, Recruiting, Krystal Biotech, Inc. | Phase classification: P1 --> P1/2 | N=80 --> 140

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

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

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Dec 2024 --> Jul 2025

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

P3, N=800, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting

P1, N=1, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2026 --> Jun 2025 | Trial primary completion date: Dec 2025 --> Jun 2024

P3, N=800, Not yet recruiting, Bristol-Myers Squibb

Nivolumab plus relatlimab demonstrated similar efficacy to nivolumab plus ipilimumab in the overall population, including most-but not all-subgroups, and improved safety in patients with untreated advanced melanoma. Results should be interpreted with caution.

P3, N=560, Recruiting, Regeneron Pharmaceuticals | Not yet recruiting --> Recruiting

P3, N=400, Recruiting, Replimune Inc. | Not yet recruiting --> Recruiting

Pts are randomly assigned (2:1) to receive treatment with BMS-986213 (Arm A: nivolumab/relatlimab) IVQ4W or monotherapy with anti-PD-1 (Arm B: nivolumab) IVQ4W for up to 12 doses. Study enrolment is ongoing. A total of 270 pts will be pre-screened for ctDNA detection with a target accrual of 54 ctDNA-positive pts, of whom 36 will be randomized to Arm A and 18 to Arm B.

P1/2, N=1499, Active, not recruiting, Bristol-Myers Squibb | Trial primary completion date: Oct 2024 --> May 2024

P2, N=54, Recruiting, University Health Network, Toronto | Initiation date: May 2024 --> Jul 2024

P1, N=1, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Jan 2027 --> Dec 2025

P1, N=90, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | N=30 --> 90

P1/2, N=1499, Active, not recruiting, Bristol-Myers Squibb | Trial primary completion date: May 2024 --> Oct 2024

P2, N=20, Not yet recruiting, Melanoma Institute Australia | Trial completion date: Apr 2036 --> Jul 2036 | Initiation date: Apr 2024 --> Jul 2024 | Trial primary completion date: Jun 2026 --> Sep 2026

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

P1/2, N=1499, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Sep 2024 --> Jan 2025 | Trial primary completion date: Sep 2024 --> May 2024

Here, we report a case of an 89-year-old patient with metastatic melanoma to the liver, lung and lymph nodes, who underwent treatment with Opdualag (combining anti-PD-1 nivolumab and anti-lymphocyte-activation gene 3 relatlimab ICBs), and developed pseudoprogression after two cycles of therapy. The patient experienced a radiographic increase in liver metastatic lesion size, but was found to have a subsequent reduction in these lesions. The patient has been on therapy for 18 months without evidence of disease progression and continues to be clinically well-appearing.

P2, N=9, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=30 --> 9

P2, N=1500, Recruiting, Bristol-Myers Squibb | N=800 --> 1500 | Trial completion date: Aug 2025 --> Aug 2029 | Trial primary completion date: Aug 2025 --> Aug 2029

P1, N=1, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | N=24 --> 1

P2, N=54, Recruiting, University Health Network, Toronto

P2; Not yet recruiting --> Recruiting

P1, N=30, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Not yet recruiting --> Recruiting

P1, N=30, Not yet recruiting, H. Lee Moffitt Cancer Center and Research Institute

P2, N=20, Not yet recruiting, Melanoma Institute Australia

P3, N=700, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting

P3, N=680, Recruiting, Immunocore Ltd | Not yet recruiting --> Recruiting

P3, N=400, Not yet recruiting, Replimune Inc.

P1/2, N=1499, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Aug 2026 --> Sep 2024

P3, N=560, Not yet recruiting, Regeneron Pharmaceuticals

P2, N=274, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed

On 18 March 2022, the U.S. FDA approved the fixed-dose combination of relatlimab developed by Bristol Myers Squibb with nivolumab, under the brand name Opdualag for the treatment of unresectable or metastatic melanoma in adult and pediatric patients aged 12 and older. This study comprehensively describes the mechanism of action and clinical trials of relatlimab and a brief overview of immune checkpoint drugs currently used for the treatment of melanoma.

P1, N=80, Active, not recruiting, TriSalus Life Sciences, Inc. | Recruiting --> Active, not recruiting

P2, N=274, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Dec 2024 --> Jan 2024

P2, N=100, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting

P2, N=20, Not yet recruiting, Melanoma Institute Australia

No safety concerns were observed compared with monotherapy with treatment-related adverse events occurring in 18.9% of patients on combination therapy compared with 9.7% on nivolumab alone. The novel mechanism and improvement in progression-free survival compared with standard of care highlight the therapeutic advancement of nivolumab/relatlimab-rmbw in the treatment of unresectable and metastatic melanoma.

With additional follow-up, the combination of favezelimab and pembrolizumab continued to demonstrate sustained antitumor activity and manageable safety in patients with anti–PD-1–naive R/R cHL. Analyses are underway to identify biomarkers predictive of response to the combination of favezelimab and pembrolizumab. Further studies to investigate this combination are warranted.