relatlimab (BMS-986016) / BMS, Ono Pharmaceutical - LARVOL DELTA

Single-cell characterization of anti-LAG3+anti-PD1 treatment in melanoma patients. (PubMed, J Clin Invest) - P1/2 | "Anti-LAG3+anti-PD1 therapy has profound effects on NK cells and Tregs in addition to CD8+ T cells."

IO biomarker • Journal • Genetic Disorders • Immunology • Melanoma • Oncology • Skin Cancer • Solid Tumor • CD8

Neoadjuvant nivolumab and relatlimab in locally advanced MMR-deficient colon cancer: a phase 2 trial. (PubMed, Nat Med) - P2 | "These data add to the body of evidence in support of neoadjuvant immunotherapy regimens in dMMR CC. ClinicalTrials.gov identifier: NCT03026140 ."

IO biomarker • Journal • Metastases • P2 data • Colon Cancer • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Oncology • Solid Tumor

Nivolumab (NIVO) plus relatlimab with platinum-doublet chemotherapy (PDCT) vs NIVO + PDCT as first-line (1L) treatment (tx) for stage IV or recurrent NSCLC: Results from the randomized phase II RELATIVITY-104 study (ESMO 2024) - P2 | "In this head-to-head proof-of-concept phase 2 study, NIVO + RELA 360 mg + PDCT demonstrated improved clinical benefit vs NIVO + PDCT, particularly in PD-L1 ≥ 1% and NSQ pre-specified subgroups. Further phase 3 investigation is warranted. Table: LBA53 a(90% CI)bPart 1 RELA 360mg dose in PD-L1 ≥ 1% & NSQ (n = 22): mPFS 10.9 mo, ORR 50.0%."

Clinical • IO biomarker • Late-breaking abstract • Metastases • P2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • LAG3 • PD-1 • PD-L1 • RELA

Rectal Mucosal Melanoma: A Rare and Aggressive Malignancy Discovered on Routine Colonoscopy (ACG 2026) - "He enrolled in a trial involving sarilumab with ipilimumab, nivolumab, and relatlimab, then transitioned to ipilimumab plus nivolumab following rapid hepatic progression. Immunotherapy has demonstrated limited efficacy in mucosal subtypes, which harbor distinct molecular profiles and lower tumor mutational burden. This case highlights the importance of thorough pathologic analysis of rectal polyps and awareness of this rare but morbid diagnosis."

IO biomarker • Tumor mutational burden • Colonic Polyps • Cutaneous Melanoma • Gastroenterology • Gastrointestinal Disorder • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • SOX10 • TMB • VIM

Predicting Targeted and Immunotherapeutic Response Outcomes in Melanoma With Single-Cell Raman Spectroscopy and Artificial Intelligence. (PubMed, JCO Precis Oncol) - "Single-cell Raman spectroscopy combined with ML offers a scalable, prognostic platform to predict therapeutic resistance likelihood, with further potential to advance clinical, multiomic biomarker efforts for melanoma. Our approach may improve first- and second-line therapy selection assessments for precision medicine by providing rapid, nondestructive prediction of therapeutic response based on cellular spectral profiles."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor

Characterization of histology-dependent immunobiological differences in metastatic NSCLC: Implications for treatment with PD-1 and LAG-3 inhibitors. (ASCO 2025) - P3 | "For example, in the RELATIVITY-104 study, addition of the LAG-3 inhibitor relatlimab to anti-PD-1 + platinum-doublet chemotherapy (PDCT) showed improved clinical benefit among patients with PD-L1 ≥1%, which was further enriched with NSQ histology... These data provide a supporting mechanistic rationale for the use of tumor histology in addition to PD-L1 expression to identify patients who would benefit from the addition of a LAG-3 inhibitor to PD-1 inhibitor + PDCT."

IO biomarker • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • LAG3 • PD-L1 • PIK3CA

Zanzalintinib (zanza) + nivolumab (nivo) ± relatlimab (rela) in patients (pts) with previously untreated clear cell renal cell carcinoma (ccRCC): Results from an expansion cohort of the phase 1b STELLAR-002 study. (ASCO 2025) - P1 | "First-line zanza had acceptable tolerability in combination with nivo or nivo/rela with a low rate of PPE; zanza+nivo showed promising preliminary activity in pts with adv/met ccRCC."

Clinical • P1 data • Clear Cell Renal Cell Carcinoma • Dermatology • Genito-urinary Cancer • Hypertension • Oncology • Solid Tumor • AXL

Nivolumab plus relatlimab and nivolumab plus ipilimumab for patients with advanced renal cell carcinoma: results from the open-label, randomised, phase II FRACTION-RCC trial. (PubMed, ESMO Open) - "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."

IO biomarker • Journal • Metastases • P2 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • LAG3 • PD-L1 • RELA

Ocular Surface Disease as an Immune-related Adverse Event of Immune Checkpoint Inhibitor Therapy. (PubMed, Cornea) - "Immune-mediated scleritis generated the strongest disproportionality signal in this analysis among PD-1 inhibitors, although these estimates are based on small case counts and wide confidence intervals and should be regarded as hypothesis-generating. Sicca syndrome and keratitis were reported across multiple ICI classes, with the keratitis signals for nivolumab and pembrolizumab supported by the largest case counts. As a disproportionality analysis, this study cannot establish incidence, comparative risk, or causality; the findings support clinical vigilance and further epidemiologic study rather than definitive causal conclusions. Physicians managing ICI-treated patients should have a low threshold for ophthalmological referral when ocular symptoms arise."

Adverse events • Checkpoint inhibition • Journal • Conjunctivitis • Dry Eye Disease • Immunology • Keratitis • Ocular Infections • Ocular Inflammation • Oncology • Ophthalmology • Scleritis • Sjogren's Syndrome • LAG3

RELATIVITY-123: A phase 3, randomized, open-label study of nivolumab (NIVO) + relatlimab (RELA) fixed-dose combination (FDC) versus regorafenib or trifluridine + tipiracil (TAS-102) in later-line metastatic colorectal cancer (mCRC). (ASCO-GI 2023) - P3 | "The study initiated in April 2022 and is enrolling globally. Clinical trial information: NCT05328908."

Clinical • Metastases • P3 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • LAG3 • MSI • PD-L1 • RELA

CONgRAtS: A randomized phase II study of nivolumab±relatlimab in patients with TLS-positive soft-tissue sarcomas (ESMO 2025) - P2 | "Both arms exceeded historical benchmarks, confirming TLS-guided immunotherapy's clinical value. High-dimensional analyses from tumor and plasma samples are underway to define response mechanisms and refine future combinatorial strategies."

Clinical • IO biomarker • P2 data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • LAG3

Neoadjuvant Nivolumab with or without Relatlimab in Resectable NSCLC: Additional Analysis and Extended Follow-up (IASLC-WCLC 2024) - P2 | "The majority of recurrences were at distant sites. All relapsed patients received subsequent therapy without new safety signals."

Clinical • Cardiovascular • Hepatology • Liver Failure • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • LAG3

Lifileucel versus Nivolumab plus Relatlimab (NIVO+RELA) in anti–PD-(L)1-resistant advanced melanoma: A match-adjusted indirect comparison (MAIC) of efficacy outcomes (ESMO 2026) - No abstract available

Clinical • Metastases • Melanoma • Oncology • Solid Tumor • RELA

Unraveling relatlimab (RELA)-specific biology: Biomarker analyses in patients (pts) with metastatic non-small cell lung cancer (mNSCLC) treated with 1L nivolumab (NIVO) + RELA high-dose (HD) and platinum-doublet chemotherapy (PDCT). (ASCO 2025) - P2 | "Funded by Bristol Myers Squibb Clinical Trial Registration Number: NCT04623775 Background: The addition of RELA HD, a lymphocyte activation gene-3 (LAG-3) inhibitor, to NIVO + PDCT has improved clinical benefits vs NIVO + PDCT for pts with PD-L1 expression ≥1% and NSQ histology in RELATIVITY-104 study. These data represent the first in-depth biomarker analyses from a randomized phase 2 study to reveal that RELA can expand proliferating LAG-3 expressing T cells in NSCLC. NIVO + RELA HD + PDCT activity might be particularly robust in pts with NSQ histology and PD-L1 expression ≥1%, where CD8 T cells are enriched. The ongoing phase 3 RELATIVITY-1093 study is evaluating 1L NIVO + RELA HD + PDCT vs standard-of-care pembrolizumab + PDCT in mNSCLC."

Biomarker • Clinical • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • LAG3 • PD-L1 • RELA

SUPRAME: A phase 3 trial comparing IMA203, an engineered T-cell receptor expressing T cell therapy (TCR-T) vs investigator's choice in patients with previously treated advanced cutaneous melanoma. (ASCO 2025) - P3 | "Following lymphodepletion with cyclophosphamide (500 mg/m2 x 4 days) and fludarabine (30 mg/m2 x 4 days), 1-10x109 IMA203 TCR-T cells will be administered, followed by low-dose IL-2 (1mio IU daily x5 days, twice daily x5 days). Patients in the control arm will receive approved investigator's choice of standard treatment (nivolumab/relatlimab, nivolumab, ipilimumab, pembrolizumab, lifileucel (US), chemotherapy)...Secondary endpoints include OS, ORR, safety and patient-reported outcomes (EORTC QLQ-C30, EQ-5D-5L). The trial will enroll patients in the US and Europe."

Clinical • IO biomarker • Metastases • P3 data • Cutaneous Melanoma • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BRAF • HLA-A • PRAME

Long-Term Survival and Biomarker Analysis Evaluating Neoadjuvant Plus Adjuvant Relatlimab (anti-LAG3) and Nivolumab (anti-PD1) in Patients With Resectable Melanoma. (PubMed, J Clin Oncol) - P2 | "Gene expression analysis of longitudinally collected biospecimens from the trial identifies baseline upregulation of several immune modulatory pathways associated with MPR; by contrast, increased B7-H3 expression was associated with resistance. This work demonstrates the long-term benefit of neoadjuvant nivolumab and relatlimab and identifies a potentially targetable predictor of resistance to this combination therapy."

Biomarker • IO biomarker • Journal • Melanoma • Oncology • Solid Tumor • CD276

A phase 2 trial of IO102-IO103 and nivolumab-relatlimab in previously untreated, unresectable melanoma. (ASCO 2026) - P2 | "IO102-IO103 in combination with nivo-rela was associated with a higher objective response rate compared to historical data for nivo-rela alone, meeting the trial's primary endpoint. No unexpected safety signals were observed. These findings support the further clinical investigation of IO102-IO103 with nivo-rela as an initial treatment for unresectable melanoma."

IO biomarker • P2 data • Acute Kidney Injury • CNS Disorders • Endocrine Disorders • Eye Cancer • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Melanoma • Myositis • Nephrology • Neutropenia • Renal Disease • Solid Tumor • PD-L1

Nivolumab combination therapies in patients with advanced gastric and gastroesophageal junction cancer: the phase II FRACTION gastric cancer study. (PubMed, ESMO Open) - "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."

Journal • P2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • IDO1 • LAG3

Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial. (PubMed, Nat Med) - P2 | "Exploratory analyses provided insights into biological processes triggered by preoperative immunotherapy. This study establishes the feasibility and safety of dual targeting of PD-1 and LAG-3 before lung cancer surgery.ClinicalTrials.gov Indentifier: NCT04205552 ."

IO biomarker • Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

The DIET study: A randomized controlled trial of a high fiber diet intervention (HFDI) in patients (pts) with melanoma receiving immune checkpoint blockade (ICB). (ASCO 2024) - P2 | "ICB tx were PD1 monotherapy (n=22), ipilimumab + nivolumab (n=16), and nivolumab + relatlimab (n=7). In this fully-controlled feeding study among melanoma pts undergoing ICB tx, both arms of the intervention were well-tolerated. In contrast to our prior studies in cancer survivor populations, we noted a significant discontinuation rate, perhaps due to the challenges of participating in a fully-controlled feeding study while undergoing active cancer therapy. Ongoing analyses are interrogating the effects of the dietary intervention on the structure and function of the gut microbiome, circulating and stool metabolites, and systemic and anti-tumor immunity."

Checkpoint block • Checkpoint inhibition • Clinical • Anorexia • Constipation • Diabetes • Gastroenterology • Gastrointestinal Disorder • Melanoma • Metabolic Disorders • Oncology • Pain • Solid Tumor

Repurposing Anticancer Drugs in Parkinson's Treatment: Molecular Pathways Driving Neuroprotection and Therapeutic Advancement. (PubMed, Mol Neurobiol) - "Ixazomib enhances α-synuclein clearance via autophagy in preclinical models. Nilotinib showed poor CNS penetration (< 0.3% in CSF), resulting in worsening motor outcomes. Relatlimab, trehalose, and lapatinib demonstrated preclinical benefits through inhibition of α-synuclein spread, mTOR-independent autophagy, and multi-pathway neuroprotection, respectively. The AZA-PD Phase 2 trial (azathioprine) demonstrated a favourable safety and tolerability profile and offered valuable insights into peripheral immune modulation in early PD, though it did not meet its primary endpoint of slowing disease progression...Mechanistic convergence provides a rationale for repurposing drugs; however, clinical success requires addressing the unique challenges of neurodegeneration. Future approaches should focus on precision medicine, innovative delivery systems, and multi-target interventions rather than direct therapeutic translation."

Journal • Review • CNS Disorders • Immune Modulation • Immunology • Metabolic Disorders • Movement Disorders • Oncology • Parkinson's Disease • Targeted Protein Degradation

Phase Ib randomized open-label trial of sacituzumab govitecan plus nivolumab or sacituzumab govitecan plus nivolumab and relatlimab as second-line therapy metastatic triple negative breast cancer: SIMONE trial. (ASCO 2026) - P1/2 | " This is an ongoing investigator-initiated randomized, open-label, phase Ib study to assess safety and efficacy of SG plus nivolumab (n= 30 patients) or SG plus a fixed dose combination (FDC) of nivolumab and relatlimab (n = 30 patients) in patients with metastatic TNBC; NCT06963905. Exploratory endpoints include overall survival, and biomarkers of prediction of response and resistance. There will be a follow-up visit after the last study treatment administration or before starting a new anticancer treatment, whichever occurs first, followed by long-term/survival chart review follow-up every three months for 2 years."

Clinical • IO biomarker • Metastases • P1 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • LAG3 • PD-L1

Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses. (PubMed, Nat Med) - P1 | "Our findings provide insights into the safety profile of combined PD-1 and LAG-3 blockade in gastroesophageal cancer and highlight the potential of ctDNA analysis to dynamically assess systemic tumor burden during neoadjuvant ICI that may open a therapeutic window for future intervention. ClinicalTrials.gov registration: NCT03044613 ."

Circulating tumor DNA • IO biomarker • Journal • P1 data • Dermatitis • Dermatology • Esophageal Cancer • Fatigue • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Disorders • Immunology • Oncology • Solid Tumor • Thrombocytopenia • LAG3 • PD-L1

A phase II study of the interleukin-6 (IL-6) receptor blocking antibody sarilumab (Sari) in combination with ipilimumab (Ipi), nivolumab (Nivo) and relatlimab (Rela) in patients with unresectable stage III or stage IV melanoma. (ASCO 2025) - P2 | "Nivo, Rela, Ipi, + Sari demonstrated encouraging efficacy and tolerability. At 24 weeks, 63.6% BORR and 12.1% gr 3/4 irAE rate were observed. 2 patients had gr 4 toxicity; no gr 5 events were reported."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Immunology • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • BRAF • IL4 • IL6

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