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

Feasibility and Efficacy of Perioperative Nivolumab With or Without Relatlimab for Patients With Potentially Resectable Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jun 2026 ➔ Dec 2026 | Trial primary completion date: Jun 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • Hepatocellular Cancer • Oncology • Solid Tumor

Multidimensional, spatially resolved immunologic hallmarks of response to neoadjuvant immune checkpoint blockade (ICB) therapies. (ASCO 2025) - " To identify robust biomarkers of response to neoadjuvant ICB, we assembled a cohort of 58 stage III melanoma patients treated with neoadjuvant ICB [24 ipilimumab-nivolumab (IPI-NIVO), 21 NIVO-relatlimab (RELA), 13 PD1 mono] and deployed transformative technologies and computational methods, including single-cell FFPE sequencing, multiplexed FISH single-cell ST (MERFISH 305 genes), digital pathology, 3D open-top light-sheet imaging and AI-based computational pathology, to decipher the complex neoadjuvant ICB tumor ecosystem in response to therapy. Our investigations herein have provided a comprehensive characterization of the immune architectures, cellular communications and 3D large-scale morphologic organizations of the TME that drive response to neoadjuvant ICB therapy. We believe the results of this study will enable the development of robust predictive biomarkers to guide the design of next generation combination ICB therapies in the clinical trial setting for..."

Checkpoint block • Checkpoint inhibition • Clinical • IO biomarker • Melanoma • Oncology • Skin Cancer • Solid Tumor • RELA

Efficacy of neoadjuvant combination immune checkpoint inhibitor therapy in patients with resectable high grade melanomas: A systematic review and meta analysis of randomised control trials. (ASCO 2025) - "This meta analysis highlights the potential of neoadjuvant chemotherapy as an effective strategy for patients with high grade resectable melanomas.Our results demonstrate that both Ipilimumab and Nivolumab and Relatlimab and Nivolumab regimens are equally effective, providing clinicians with flexibility in treatment selection based on patient-specific factors. RCTs with more sample size are needed to arrive at more definite conclusions."

Checkpoint inhibition • Retrospective data • Review • 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

Real-world outcomes in patients with brain metastases secondary to melanoma treated with nivolumab/relatlimab. (ASCO 2025) - "The combination of anti-PD1 (nivolumab, nivo) and anti-cytotoxic T-lymphocyte antigen-4 (ipilimumab, ipi) has demonstrated the highest intracranial and extracranial response rates and durability. The combination of nivo-rela showed intracranial activity in patients with MBM, particularly in the 1L. Prospective trials are needed to confirm these findings and provide data on the optimal use of systemic and local therapies in this challenging patient population. Patient Demographics"

Clinical • IO biomarker • Real-world • Real-world evidence • Melanoma • Oncology • Solid Tumor

Zanzalintinib (zanza) + nivolumab (nivo) ± relatlimab (rela) in patients (pts) with advanced solid tumors: Results from two dose-escalation cohorts of the phase 1b STELLAR 002 study. (ASCO 2025) - P1 | "The tolerability of zanza + nivo and zanza + nivo/rela was manageable and consistent with each monotherapy agent. Preliminary safety, PK, and response data support selection of the 100-mg zanza dose in combination with nivo or nivo/rela for further investigation. Expansion cohorts are ongoing in various tumor types."

Clinical • Metastases • P1 data • Colorectal Cancer • Dermatology • Fatigue • Genito-urinary Cancer • Hypertension • Oncology • Prostate Cancer • Renal Cell Carcinoma • 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

Clinical outcomes of the DIET study: A randomized controlled phase 2 trial of a high fiber diet intervention (HFDI) in patients with melanoma receiving immune checkpoint blockade (ICB). (ASCO 2025) - P2 | "ICB regimens include pembrolizumab or nivolumab monotherapy (n = 19), ipilimumab + nivo (n = 16), and nivo + relatlimab (n = 7). Our study suggests potential benefits of HFDI on clinical outcomes and toxicity profile with ICB, warranting further study in Phase III trials powered for disease outcomes."

Checkpoint block • Checkpoint inhibition • Clinical • Clinical data • P2 data • Melanoma • Oncology • Solid Tumor

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

Clinical and biomarker analyses of first-line nivolumab and relatlimab (nivo-rela) in advanced or resectable melanoma (mel). (ASCO 2025) - "In a real-world setting, first-line nivo-rela in advanced mel resulted in potentially better PFS while in resectable pts the major pathologic response rate was lower than previously reported in clinical trials. Mel TME with high B7-H3 protein expression was enriched with M2-skewed macrophages and fibroblasts in association with non-response to nivo-rela. This finding warrants further investigation of B7-H3 targeting agents in mel pts"

Biomarker • Clinical • IO biomarker • Metastases • Cardiovascular • Endocrine Disorders • Melanoma • Nephrology • Oncology • Renal Disease • Solid Tumor • CD14 • CD163 • CD68 • CD8 • CTLA4 • FAP • LAG3 • PD-L1

A randomized, controlled, multicenter, phase 3 study of vusolimogene oderparepvec combined with nivolumab vs treatment of physician's choice in patients with advanced melanoma that has progressed on anti–PD-1 and anti–CTLA-4 therapy (IGNYTE-3). (ASCO 2025) - P2, P3 | "Among available treatments, combination anti–PD-1 (nivolumab) + anti–CTLA-4 (ipilimumab) therapy is associated with the highest ORR and best PFS and OS...Vusolimogene oderparepvec (VO; also known as RP1) is a selectively replication-competent herpes simplex virus type 1–based oncolytic immunotherapy that expresses human granulocyte-macrophage colony-stimulating factor and a fusogenic glycoprotein (GALV-GP-R–)...Patients (N = ~400) will receive VO + nivolumab or physician's choice (nivolumab + relatlimab, anti–PD-1 monotherapy rechallenge [nivolumab or pembrolizumab], or single-agent chemotherapy [dacarbazine, temozolomide, or paclitaxel/albumin-bound paclitaxel]). The primary endpoint of the study is OS; the key secondary endpoints are PFS and ORR per RECIST 1.1."

Clinical • IO biomarker • Metastases • P3 data • Cutaneous Melanoma • Herpes Simplex • Melanoma • Oncology • Solid Tumor

Phase I/Ib study of concurrent intravenous (IV) and intrathecal (IT) nivolumab (N) and relatlimab (R) for metastatic melanoma (MM) patients (pts) with leptomeningeal disease (LMD). (ASCO 2025) - P1 | "Most pertinent inclusion criteria are radiographic and/or CSF cytological evidence of LMD, ECOG PS of ≤ 2, ≤ 4 mg per 24 hours of dexamethasone (or the equivalent), with adequate organ function. CSF, blood and microbiome samples will be collected at various time points. The first patient was enrolled in October 2024 and accrual of patients is ongoing (NCT03025256)."

Clinical • IO biomarker • Metastases • P1 data • Melanoma • Oncology • Solid Tumor • CD8

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

Phase I/IIa dose finding study of triplet regimen of relatlimab (RELA), ipilimumab (IPI), and nivolumab (NIVO) in first-line therapy of metastatic melanoma (TRINITY). (ASCO 2025) - P1/2 | "Safely biopsiable lesions are required for pts enrolled in the PhII portion. This study is open for accrual at MD Anderson Cancer Center in Houston, Texas."

Clinical • Metastases • P1/2 data • Melanoma • Oncology • Solid Tumor • RELA

Real-world comparison of survival with nivolumab (NIVO) + relatlimab (RELA) vs NIVO + ipilimumab (IPI) in advanced melanoma. (ASCO 2025) - "This real-world study supports the ITC observation that NIVO + RELA and NIVO + IPI convey similar OS benefits for pts with advanced melanoma. The longer rwPFS for NIVO + RELA vs NIVO + IPI warrants additional research with longer follow-up and further evaluation of baseline characteristics, as the NIVO + IPI group had poorer prognostic factors. Important limitations included short follow-up, covariate missingness, and potential unmeasured confounding."

Clinical • Metastases • Real-world • Real-world evidence • Melanoma • Oncology • Solid Tumor • BRAF • PD-L1 • RELA

A phase 2 study to determine the clinical and pathological (path) response to neoadjuvant nivolumab (nivo) and relatlimab (rela) in stage II to IV (M0) resectable cutaneous squamous cell carcinoma (Neo-SCC). (ASCO 2025) - P2 | "In a larger NAT cemiplimab trial (N = 79) 51% pts achieved pCR (Gross et al...The De-Squamate cuSCC trial, evaluating NAT anti-PD1 monotherapy with pembrolizumab (N = 27), showed a 63% combined rate of pCR and clinical complete response (CCR) resulting in the de-escalation of surgery and post operative radiotherapy (RT) in 48% of pts, and avoidance of post-operative RT in 15% of pts (Ladwa et al...The sample size is powered to detect a difference > 25% in pCR rate with the historical control. Secondary endpoints include surgical/RT de-scalation rates, RFS, OS, safety/tolerability, surgical outcomes, QOL, and biomarker analyses."

Clinical • IO biomarker • P2 data • Genetic Disorders • Melanoma • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • LAG3

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

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

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

Neotrace: A multicenter phase II study of neoadjuvant sacituzumab govitecan plus zimberelimab followed by adjuvant zimberelimab with or without sacituzumab govitecan in patients with resectable non-small cell lung cancer. (ASCO 2025) - "Recent data from studies such as NEOpredict (which demonstrated a 100% surgical completion rate with neoadjuvant nivolumab with/without relatlimab), NeoCOAST-2 (which reported a 34% pathological complete response [pCR] rate using a neoadjuvant combination of an anti-TROP2 antibody drug conjugate [ADC], IO, and single-agent platinum, thereby surpassing the ~20% pCR rates achieved with neoadjuvant chemoimmunotherapy), and EVOKE-02 (which showed promising objective response rates of 69% and 44% with the anti-TROP2 ADC sacituzumab govitecan plus pembrolizumab in first-line metastatic NSCLC patients with PD-L1 ≥50% and PD-L1 0-49%, respectively) demonstrate that chemotherapy-sparing approaches may reduce toxicity while maintaining or enhancing efficacy. As of June 2025, the NeoTRACE study is recruiting 50 patients across 15 sites in Germany. EudraCT: 2024-517561-16."

Clinical • IO biomarker • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor • ALK • EGFR • PD-L1 • TACSTD2

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

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

Successful use of nivolumab and relatlimab as salvage therapy for metastatic uveal melanoma. (PubMed, Melanoma Res) - "In this case report, we present two heavily pretreated patients with metastatic uveal melanoma who had robust responses to combination nivolumab (PD-1 inhibitor) with relatlimab (LAG-3 inhibitor) as salvage treatment. We highlight the ongoing research of the uveal melanoma tumor immune microenvironment and the potential role of LAG-3 inhibition as an effective treatment strategy."

Journal • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • LAG3

A Phase II, Multicentre, Open Label, Randomised Clinical Trial of Nivolumab and Ipilimumab Combined With Relatlimab for Patients With Resectable Advanced Melanoma Identified as Poor Responders to Immunotherapy Neo IRENIE (NEOadjuvant Ipilimumab, RElatlimab, NIvolumab Evaluation) (clinicaltrials.gov) - P2 | N=297 | Not yet recruiting | Sponsor: Melanoma Institute Australia

IO biomarker • New P2 trial • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor