Opdualag (nivolumab/relatlimab)

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.

P3, N=680, Not yet recruiting, Immunocore Ltd

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

OBJECTIVES: Due to lack of head-to-head randomized clinical trials comparing NIVO+RELA vs BRAF/MEK inhibitors for first-line treatment of BRAF-mutant aMel, we evaluated the efficacy of NIVO+RELA vs dabrafenib+trametinib (DAB+TRAM), encorafenib+binimetinib (ENCO+BINI), and vemurafenib+cobimetinib (VEM+COBI) via MAICs... These MAICs suggest long-term (after 12 months) OS advantage of NIVO+RELA over DAB+TRAM, ENCO+BINI, and COBI+VEM for first-line treatment of BRAF-mutant aMel.

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

Palliative therapy with Opdualag (Nivolumab-Relatlimab) was initiated. These cases emphasize the importance of considering primary melanoma as a possible diagnosis when evaluating patients with GI manifestations and no history of cutaneous melanoma. Figure: Colonoscopy and Endoscopy finding images

Upon confirmation of metastatic melanoma to the stomach and lungs, the patient was initiated on immunotherapy regimen of Nivolumab and Relatlimab-rmbw. Therefore, close attention to GI symptoms followed by imaging and endoscopic evaluation can result in earlier intervention and progression-free survival. Figure: Left: PET scan with relative thickening of the mid to distal gastric walls with associated focal uptake Right: EGD findings of two ulcerated polypoid masses in the anterior wall of the stomach measuring 4cm (top) and 1.5cm (bottom)

Additional analyses will be presented. Table: 1103P

Table: LBA51 Select changes in peripheral blood 4 weeks post first dose suggesting RELA-specific activity NIVO NIVO+RELA %Δa P %Δa P sLAG-3+ CD4+FoxP3− (conventional) 0 NS 166.7 **** sLAG-3+ CD4+ 16.7 NS 142.9 **** sLAG-3+ naïve CD4+ −9.10 NS 40.0 **** sLAG-3+ TE CD8+ 12.5 NS 491.7 **** cLAG-3+ TE CD8+ 5.9 NS 66.7 **** sLAG-3+ naïve CD8+ 0 NS 60.0 **** CD38+ HLADR+ TE CD8+ 7.4 NS 30.8 *** sLAG-3+ CD56+ CD16+ (int) NK 9.10 NS 117.4 **** sLAG-3+ NK 0 NS 50.0 **** sLAG-3+ CD56− CD16+ (mature) NK 10.5 NS 40.2 ** aMedian.c, cytoplasmic; int, intermediate; NS, nonsignificant; s, surface; TE, terminal effector. *<0.05; **<0.01; ***<0.001; ****<0.0001 by Wilcoxon test.

No abstract available

Ongoing trials are studying the combination of LAG-3 antibodies with PD-1 inhibitors in multiple cancers and settings. The low toxicity of the combination may also allow for further layering of additional therapeutic approaches such as chemotherapy, oncolytic viruses, cellular therapies, and possibly novel cytokines, among others.

P1, N=36, Recruiting, Carlo Contreras | Trial completion date: Dec 2024 --> Dec 2025

P1, N=24, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Initiation date: Jan 2023 --> Jun 2023

This manuscript, describing the pharmacological aspects of eleven anticancer novel drug therapies approved by the FDA, shall serve as a helpful document for cancer patients, concerned academicians, researchers, and clinicians, especially oncologists.

P2, N=43, Recruiting, Memorial Sloan Kettering Cancer Center

Ongoing clinical trials studying the use of relatlimab and associated areas of active investigation are also highlighted. This review strives to inform practicing dermatologists on the use of relatlimab-nivolumab as an approved first-line dual checkpoint inhibitor for metastatic melanoma in appropriate clinical cases.

Results from the RELATIVITY-047 trial show that the PFS benefit with NIVO + RELA FDC over NIVO was obtained with stable patient-reported HRQoL, supporting NIVO + RELA as a first-line treatment option for patients with advanced melanoma.

P1/2, N=1499, Active, not recruiting, Bristol-Myers Squibb | Trial primary completion date: Sep 2023 --> Sep 2024

P1/2, N=24, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting

Dual inhibition therapy in the RELATIVITY-047 trial significantly improved progression-free survival in metastatic melanoma. This article discusses the presence of a possible synergistic interaction between LAG-3 and PD-1 in the tumor microenvironment and the utility of targeting both immune checkpoint inhibitors as an effective way to bypass resistance and increase treatment efficacy.

While the safety profile is more favorable than that of ipilimumab plus nivolumab, no significant survival benefit has yet been demonstrated with the new combination over nivolumab monotherapy. The approval of relatlimab plus nivolumab by both the Food and Drug Administration and the European Medicines Agency expands the arsenal of treatment options for melanoma but raises new questions in clinical practice and a re-evaluation of currently established treatment standards and sequences.