Opdualag (nivolumab/relatlimab-rmbw) / BMS, Ono Pharma - LARVOL DELTA

Nivolumab plus relatlimab in advanced melanoma: RELATIVITY-047 4-year update. (PubMed, Eur J Cancer) - P2/3 | "With 4 years of follow-up, nivolumab plus relatlimab demonstrated durable improvement in outcomes versus nivolumab monotherapy for patients with previously untreated advanced melanoma. The durable benefit observed comes at a lower toxicity cost compared with other immuno-oncology combinations."

Journal • Melanoma • Oncology • Solid Tumor

Nivolumab/relatlimab versus nivolumab/ipilimumab for metastatic melanoma: A retrospective, propensity-matched cohort study. (ASCO 2025) - "These results indicate that in the treatment of advanced melanoma with dual checkpoint inhibitor therapy, the combination of relatlimab plus nivolumab confers improved mortality at three years over ipilimumab plus nivolumab. One limitation of this study is that we were not able to control for molecular markers including PDL-1 status, mutational profile, or extent of metastatic disease. Further research including prospective studies accounting for these factors will be needed to confirm these results."

IO biomarker • Metastases • Retrospective data • Melanoma • Oncology • Solid Tumor • PD-L1

Long-term follow-up of patterns of melanoma early and late recurrence after adjuvant anti-PD1 therapy. (ASCO 2025) - "Of the 60 pts who received systemic therapy only after recurrence, ORR to rechallenge w aPD1, anti-CTLA4 + aPD1, targeted therapy +/- aPD1, TVEC/other injectables +/- aPD1, Opdualag and chemo were 57%, 26%, 62%, 30%, 0% and 0%; including those w early PD, ORR of 0% (0/2), 25% (5/20), 63% (5/8), 22% (2/9), 0% (0/1) and NA; and w late PD, ORR of 80% (4/5), 29% (2/7), 60% (3/5), 100% (1/1), 0% (0/1) and 100% (1/1)... With the known longest follow up, half of pts w high risk resected melanoma developed PD after adj aPD1, and 2/3rds of those are early PD. Half of resectable relapse can be managed by sx followed by adj ICI w/o further PD. Most of the late PD rechallenged w aPD1 can still respond."

Clinical • Melanoma • Oncology • Solid Tumor

Nivolumab plus relatlimab vs nivolumab alone for the adjuvant treatment of completely resected stage III–IV melanoma: Primary results from RELATIVITY-098. (ASCO 2025) - P3 | "NIVO + RELA did not result in significant RFS improvement vs NIVO alone as adjuvant treatment for pts after complete resection of stage III–IV melanoma. The safety profile of NIVO + RELA in this setting was generally consistent with results from RELATIVITY-047. A robust biomarker analysis for the study is currently underway."

Clinical • Late-breaking abstract • Melanoma • Oncology • Solid Tumor • RELA

RELATIVITY-020: Intracranial (IC) activity of nivolumab + relatlimab (NIVO + RELA) in patients (pts) with PD-(L)1 refractory melanoma with melanoma brain metastases (MBM). (ASCO 2025) - P1/2 | "Pts had a median (range) of 2 (1–10) prior therapies, including anti-PD-(L)1 (100%), anti-CTLA-4 (63%, including 44% NIVO + ipilimumab), BRAF/MEKi (26%), and brain radiotherapy (81%, with 26% receiving the radiotherapy < 3 mo prior to first dose)... A previous Part D report of this study showed a heavily pre-treated anti-PD-(L)1 refractory melanoma pt population with 12% ORR in response to NIVO + RELA irrespective of tumor location; here a subpopulation of similar pts with IC lesions compared favorably: 22% ORR and 63% CBR per CNS-specific modified RECIST v1.1. Prospective and larger studies are needed to confirm these findings. aCR+PR; bCR+PR+SD; CR, complete response; IC, intracranial; NR, not reached; PD, progressive disease; PR, partial response; SD stable disease; UTD, unable to determine."

Clinical • IO biomarker • Hepatology • Melanoma • Oncology • Solid Tumor • BRAF • RELA

Randomized dose evaluation of nivolumab + relatlimab (NIVO + RELA) in patients (pts) with advanced melanoma: Results from RELATIVITY-020. (ASCO 2025) - P1/2 | "Although the 480/480 dose yielded higher ORR and LAG-3 occupancy levels than the 480/160 dose, it did not translate into improved survival outcomes or differences in Th1 cytokine levels. The 1L 480/480 dose also led to a higher rate of d/c due to TRAEs than the 480/160 dose. RF 480/480 dosing yielded similar results to RF 480/160 dosing from RELATIVITY-020 Part D. NR, not reached."

Clinical • Metastases • Melanoma • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • LAG3 • RELA

Efficacy and safety of first-line (1L) nivolumab plus relatlimab (NIVO + RELA) versus NIVO plus ipilimumab (NIVO + IPI) in advanced melanoma: An updated indirect treatment comparison (ITC) with 4-year follow-up data. (ASCO 2025) - "Consistent with previous results, this updated ITC with longer follow-up from RELA-047 suggests that 1L treatment with NIVO + RELA may have comparable efficacy to NIVO + IPI in pts with advanced melanoma, including most—but not all—subgroups. Results should be interpreted with caution given differences in study design and changes in the treatment landscape over time. Efficacy outcomes after weighting.NR: not reached; HR/OR are NIVO+RELA vs NIVO+IPI."

Clinical • IO biomarker • Metastases • Melanoma • Oncology • Solid Tumor • BRAF • RELA

“Based on the review of the data on safety and efficacy, the benefit-risk balance of Opdualag (nivolumab/relatlimab) in the approved indication(s) remains unchanged.” (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC) Minutes of meeting on 7 – 10 Apr 2025: “Nevertheless, the product information should be updated to include myasthenia gravis as a warning and as an undesirable effect with a frequency ‘uncommon’. In addition, the product information should be updated to reflect the available data regarding the safety of patients with pre-existing autoimmune disease (AID). Therefore, the current terms of the marketing authorization(s) should be varied”

PRAC • Melanoma • Oncology • Skin Cancer • Solid Tumor

ASCO: Bristol Myers CMO brushes off LAG-3 concern in lung cancer after Opdualag’s adjuvant melanoma flop (Fierce Pharma) - P3 | N=1,190 | RELATIVITY-098 (NCT05002569) | Sponsor: Bristol-Myers Squibb | "Despite its success in advanced melanoma, Bristol Myers Squibb’s fixed-dose PD-1/LAG-3 combo, Opdualag, failed to move the needle in resected skin cancer...At a minimum follow-up of 23.4 months, Opdualag—a combo of Opdivo and the LAG-3 antibody relatlimab—showed no difference from Opdivo alone in terms of patients' risk of disease recurrence or death. About 39% of patients in both arms of the trial had experienced recurrence or passed away...At the two-year mark, 62% of patients in the Opdualag arm remained alive without recurrence, versus 63.6% in the Opdivo group. The median recurrence-free survival time was not reached for the Opdualag arm, while it was 33.1 months for the control group....Two treatment-related deaths happened in the 547-patient Opdualag arm, compared with one case in the 546-subject Opdivo arm."

P3 data • Melanoma • Skin Cancer

Cost per outcome of nivolumab + relatlimab vs BRAF + MEK inhibitor combinations for first-line treatment of BRAF-mutant advanced melanoma. (PubMed, J Manag Care Spec Pharm) - "To compare the health care costs, cost per progression-free life-year (PFLY), and cost per life-year (LY) of NIVO + RELA vs dabrafenib plus trametinib (DAB + TRAM), encorafenib plus binimetinib (ENCO + BINI), and vemurafenib plus cobimetinib (VEM + COBI) as 1L treatment for BRAF-mutated, unresectable or metastatic melanoma...NIVO + RELA showed improved LYs and PFLYs at lower cost than all 3 BRAFi/MEKi comparators over 5 years. These results support the economic value of NIVO + RELA for patients with previously untreated, BRAF-mutated, unresectable or metastatic melanoma."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor • RELA

Indirect Comparisons Shows Relatlimab/Nivolumab Has Comparable Outcomes to Ipilimumab/Nivolumab in Advanced Melanoma (OncLive) - P2/3 | N=714 | RELATIVITY-047 (NCT03470922) | Sponsor: Bristol-Myers Squibb | "Findings presented in a poster presentation at the 2025 ASCO Annual Meeting showed that after balancing key baseline characteristics for the nivolumab/relatlimab (n = 339) and nivolumab/ipilimumab groups (n = 297), investigator-assessed progression-free survival (PFS; HR, 1.08; 95% CI, 0.89-1.33) and overall survival (OS; HR, 0.95; 95% CI, 0.76-1.19) outcomes after weighting were similar between both groups. The median PFS in each arm, respectively, was 12.0 months (95% CI, 8.2-17.1) vs 11.2 months (95% CI, 8.5-18.1). Additionally, the median OS was 64.5 months (95% CI, 38.6-not reached [NR]) with relatlimab vs NR (95% CI, 37.1-NR) with ipilimumab."

P2/3 data • Melanoma

Neo-MCC: Neoadjuvant Nivolumab and Relatlimab in Merkel Cell Carcinoma (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Melanoma Institute Australia | Trial primary completion date: Apr 2026 ➔ Dec 2026

Trial primary completion date • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

RELATIVITY-098: A Study to Assess Adjuvant Immunotherapy With Nivolumab Plus Relatlimab Versus Nivolumab Alone After Complete Resection of Stage III-IV Melanoma (clinicaltrials.gov) - P3 | N=1190 | Terminated | Sponsor: Bristol-Myers Squibb | Trial completion date: Nov 2029 ➔ Apr 2025 | Active, not recruiting ➔ Terminated; Inability to meet protocol objectives

Monotherapy • Trial completion date • Trial termination • Melanoma • Oncology • Solid Tumor

Safety and efficacy of pembrolizumab plus personal dendritic cell vaccines in elderly patients with metastatic melanoma (AACR 2025) - P1b | "An 82-year-old male with stage 4c received pembrolizumab while DC-ATA was manufactured, then because of new brain metastases, received opdualag with DC-ATA. In elderly patients with advanced melanoma, it appears that DC-ATA can be administered concurrently with anti-PD-1 without increased toxicity and with no decrease in efficacy. Additional testing of this combined immunotherapy is warranted."

Clinical • Metastases • Melanoma • Oncology • Solid Tumor • CSF2 • IL4

Mice humanized for the immune system as validated tool for therapeutic antibody development (AACR 2025) - "We developed the human A375 melanoma model in huCD34+ NCG mice to evaluate the combination strategy of relatlimab (anti-LAG-3 antibody) and nivolumab (anti-PD-1 antibody) approved at the beginning of 2024 as a first-line treatment for specific melanoma indications...We also developed huPBMC mice that exhibit exclusively T-cell lineage and are suitable option to evaluate T-cell engagers like the CD3xEpCAM bispecific antibody, solitomab...Mice humanized for the immune system exhibiting either multiple lineages (CD34+ huNCG) or just T-cell lineage (huPBMC) proved themselves suitable tools to assess non-mouse cross-reactive anti-tumor immunotherapy assets. Expertise in handling such models and deep knowledge in their benefits and limitations are required to selecting the most valuable model to perform preclinical studies predictive of human therapeutic response."

Preclinical • Breast Cancer • Melanoma • Oncology • Solid Tumor • CD34

Opdualag: Data readout from P3 RELATIVITY-1093 trial (NCT06561386) for stage 4 recurrent non-squamous 1L NSCLC in 2030 (Bristol-Myers Squibb) - Q1 2025 Results

P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Oncology

Opdualag: Data readout from P3 RELATIVITY-127 trial (NCT05625399) for 1L melanoma in H2 2025 (Bristol-Myers Squibb) - Q1 2025 Results

P3 data • Melanoma • Oncology

A Study to Evaluate Whether Participants With Melanoma Prefer Subcutaneous vs Intravenous Administration of Nivolumab and Nivolumab + Relatlimab Fixed-dose Combinations (clinicaltrials.gov) - P2 | N=100 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Trial primary completion date: Aug 2025 ➔ Apr 2025

Trial primary completion date • Melanoma • Oncology • Solid Tumor

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=245 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | N=178 ➔ 245

Enrollment change • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Trial of Relatlimab, Nivolumab, and Ipilimumab in Patients With Asymptomatic and Symptomatic Melanoma Brain Metastases (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Stanford University | Initiation date: Feb 2025 ➔ Jul 2025

Trial initiation date • Melanoma • Oncology • Solid Tumor

CA209-6D9: Pilot Study of Nivolumab w/Ipilimumab or Relatlimab in Surgically Resectable Melanoma Brain Metastases (clinicaltrials.gov) - P1 | N=1 | Completed | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting ➔ Completed | N=16 ➔ 1 | Trial completion date: Jun 2025 ➔ Aug 2024

Enrollment change • Trial completion • Trial completion date • Melanoma • Oncology • Solid Tumor

A Randomized Phase 2 Trial of Nivolumab, Relatlimab Plus Ipilimumab vs. Nivolumab Plus Ipilimumab in First-line Advanced Renal Cell Carcinoma (RCC) (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Suspended ➔ Recruiting

Enrollment open • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A Phase 3 trial of fixed-dose combination of fianlimab + cemiplimab vs relatlimab + nivolumab in patients with unresectable or metastatic melanoma (EADO-WCM 2025) - P1, P3 | "Methods This is a randomised, open-label, multicentre (in ∼80 sites across North America), Phase 3 trial (NCT06246916), the fixed-dose combination (FDC) of fianlimab + cemiplimab versus the FDC of relatlimab + nivolumab will be compared in pts with unresectable/metastatic melanoma. Additional endpoints include duration of response, disease control rate, investigator-assessed ORR and PFS, safety, pharmacokinetics and immunogenicity. Results N/A Conclusions N/A"

Clinical • Metastases • P3 data • Melanoma • Oncology • Solid Tumor • PD-L1

A Randomized Phase 2 Trial of Nivolumab, Relatlimab Plus Ipilimumab vs. Nivolumab Plus Ipilimumab in First-line Advanced Renal Cell Carcinoma (RCC) (clinicaltrials.gov) - P2 | N=15 | Suspended | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Suspended

Trial suspension • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

RELATIVITY-020: An Investigational Immuno-therapy Study to Assess the Safety, Tolerability and Effectiveness of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors (clinicaltrials.gov) - P1/2 | N=1499 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed

Trial completion • Bladder Cancer • Cervical Cancer • Colorectal Cancer • Gastric Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor