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

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

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

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

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

Agilent PD-L1 IHC 28-8 pharmDx Receives EU IVDR Certification as a Companion Diagnostic Test for Non-small Cell Lung Cancer and Melanoma Indications (Businesswire) - "Agilent Technologies Inc...announced its PD-L1 IHC 28-8 pharmDx kit has received two new companion diagnostic indications approvals under EU IVDR1, expanding the eligibility of treatment to early-stage non-small cell lung cancer (NSCLC) and previously untreated advanced melanoma patients....PD-L1 IHC 28-8 pharmDx is approved for exclusive use with the Agilent Autostainer Link 48 advanced staining solution....When used in conjunction with the PD-L1 IHC 28-8 pharmDx as a companion test, in the European Union: (a) resectable NSCLC patients with PD-L1 expression ≥1% and at high risk of recurrence may be eligible for treatment with Bristol Myers Squibb’s OPDIVO (nivolumab) in combination with platinum based chemotherapy; and (b) patients 12 years of age and older with tumor cell PD-L1 expression < 1% that have previously untreated advanced (metastatic or unresectable) melanoma may be eligible for treatment with Bristol Myers Squibb’s Opdualag (nivolumab and relatlimab)."

Diagnostic • Melanoma • Non Small Cell Lung Cancer • Oncology

RELATIVITY-047: A Study of Relatlimab Plus Nivolumab Versus Nivolumab Alone in Participants With Advanced Melanoma (clinicaltrials.gov) - P2/3 | N=714 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Dec 2025 ➔ Dec 2030

Trial completion date • Melanoma • Oncology • Solid Tumor

CA209-1451: Neoadjuvant Opdualag Versus Nivolumab for Resectable High-Risk Basal Cell Carcinoma (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: University of California, San Diego | Trial completion date: Feb 2028 ➔ May 2028 | Initiation date: Jan 2025 ➔ May 2025 | Trial primary completion date: Feb 2028 ➔ May 2028

Trial completion date • Trial initiation date • Trial primary completion date • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Pseudoprogression in patients with metastatic melanoma treated with Nivolumab-Relatlimab (Opdualag): our experience. (EADO-WCM 2025) - "Further studies are needed to better characterize the features and frequency of pseudoprogression and to explore whether it may be associated with long-term responses or specific toxicities. Our observation suggest that pseudoprogression may occur more frequently under nivolumab-relatlimab treatment than with other ICIs, potentially reflecting a unique mechanism related to LAG-3 blockade"

Clinical • IO biomarker • Metastases • Endocrine Disorders • Gastrointestinal Disorder • Melanoma • Musculoskeletal Pain • Nephrology • Oncology • Renal Disease • Solid Tumor • BRAF • PD-L1

Opdualag-Associated Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits: A Case Report (NKF-SCM 2025) - "Immunotherapy was discontinued, and treatment with prednisone resulted in improved renal function, allowing for discontinuation of dialysis.Results This case is the first known instance of Opdualag-associated PGNMID. The patient's underlying conditions may have predisposed him to renal injury, exacerbated by immune checkpoint inhibition.Conclusion This case underscores the importance of recognizing immune checkpoint inhibitor-related kidney injury and the role of renal biopsy in diagnosis. Early detection and management, including the discontinuation of immunotherapy and initiation of corticosteroids, can lead to favorable outcomes in patients with PGNMID."

Case report • Clinical • Cardiovascular • Chronic Kidney Disease • Diabetes • Glomerulonephritis • Hematological Malignancies • Hypertension • Lupus Nephritis • Melanoma • Metabolic Disorders • Monoclonal Gammopathy • Nephrology • Oncology • Pulmonary Disease • Renal Disease • Solid Tumor

Erratum: First-Line Nivolumab Plus Relatlimab Versus Nivolumab Plus Ipilimumab in Advanced Melanoma: An Indirect Treatment Comparison Using RELATIVITY-047 and CheckMate 067 Trial Data. (PubMed, J Clin Oncol) - No abstract available

Journal • Melanoma • Oncology • Solid Tumor

RELATIVITY-127: A Study of Subcutaneous Nivolumab + Relatlimab Fixed-dose Combination (FDC) in Previously Untreated Metastatic or Unresectable Melanoma (clinicaltrials.gov) - P3 | N=570 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2025 ➔ Nov 2027

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

Single-cell transcriptomic landscape indicates the potential role of immunotherapy in metastatic pancreatic angiosarcoma (ENETS 2025) - "CONCLUSION Our findings outlined an immunosuppressive and angiogenic tumour ecosystem in pancreatic angiosarcoma liver metastasis. However, immunotherapies targeting LAG3, PD-L1 and CD86 (e.g., Isatuximab, Opdualag and Abatacept) and anti-angiogenic agents may be therapeutically effective and worthy of subsequent exploration."

Metastases • Angiosarcoma • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • CD86 • CDK4 • CTLA4 • EGFR • HIF1A • LAG3 • PD-1

Bristol Myers Squibb Reports Fourth Quarter and Full-Year Financial Results for 2024 (Businesswire) - "Growth Portfolio worldwide revenues increased to $22.6 billion compared to $19.4 billion in the prior year period, representing growth of 17% on a reported basis, or 19% when adjusted for foreign exchange impacts. Growth Portfolio revenues were primarily driven by higher demand for Reblozyl, Breyanzi, Camzyos and Opdualag."

Commercial • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Mantle Cell Lymphoma • Melanoma • Myelodysplastic Syndrome

Bristol Myers Squibb Provides Update on Phase 3 RELATIVITY-098 Trial (Businesswire) - "Bristol Myers Squibb...announced the Phase 3 RELATIVITY-098 trial evaluating Opdualag (nivolumab and relatlimab-rmbw) for the adjuvant treatment of patients with completely resected stage III-IV melanoma did not meet its primary endpoint of recurrence-free survival (RFS). The safety profile of Opdualag observed in this analysis was consistent with the known profiles of nivolumab and relatlimab....'Patients whose tumors are completely resected before treatment may not have sufficient antitumor T cells in place for Opdualag to have its maximal effect'."

P3 data • Melanoma

CA236-0001: A Study of BMS-986482 Alone or as Combination Therapy in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=413 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • 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 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Trial primary completion date: Feb 2026 ➔ Dec 2024

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

Orphan Drug Designations and Approvals (FDA) - Generic Name: nivolumab and relatlimab-rmbw, Trade Name: Opdualag, Date Designated: 08/18/2017, Orphan Designation: Treatment of stage IIb to IV melanoma, Orphan Designation Status: Designated/Approved.

Orphan drug • Melanoma

OPAL-1: A Study Assessing KB707 for the Treatment of Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=240 | Recruiting | Sponsor: Krystal Biotech, Inc. | N=140 ➔ 240 | Trial completion date: Jul 2026 ➔ Jul 2027 | Trial primary completion date: Jul 2026 ➔ Jul 2027

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

SUPRAME-ACTengine® IMA203 vs. Investigator's Choice of Treatment in Previously Treated, Unresectable or Metastatic Cutaneous Melanoma (clinicaltrials.gov) - P3 | N=360 | Recruiting | Sponsor: Immatics US, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Cutaneous Melanoma • Melanoma • Oncology • Skin Cancer • Solid Tumor