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

From Survival to Side Effects: Retrospective Analysis of Adverse Events in Checkpoint Inhibitor Therapy for Melanoma Using the FAERS Database (EADV 2025) - "Reports were included if the indication was malignant or metastatic melanoma and the treatment involved checkpoint inhibitors (Nivolumab, Pembrolizumab, Cemiplimab, Atezolizumab, Avelumab, Durvalumab, Ipilimumab, Tremelimumab, or Relatlimab). This study provides the most comprehensive FAERS-based analysis to date of checkpoint inhibitor- associated adverse events in melanoma treatment. While PD-1 inhibitors dominate current usage, significant differences in AE profiles, fatality rates, and geographic patterns exist across drug classes. These findings can guide clinicians in personalized risk assessment and AE monitoring strategies for patients undergoing immunotherapy."

Adverse events • Checkpoint inhibition • Retrospective data • Cardiovascular • Melanoma • Oncology • Solid Tumor • LAG3

Molecularly-guided phase 2 umbrella trial for children and young adults with newly-diagnosed high-grade glioma (HGG) including diffuse intrinsic pontine glioma (DIPG): CONNECT TarGeT (Targeted pediatric HGG therapy) trial in progress (WFNOS 2025) - P, P2 | "The following TarGeT treatment arms (most involving upfront radiotherapy), are open or soon to open, selected based on prevalence of targets in HGG/DIPG, relevant pre-clinical and clinical data, established pediatric safety data, and prioritizing combinations: (A) ribociclib and everolimus (target: cell cycle or PI3K//mTOR pathway alterations) [NCT05843253], (A-2) ribociclib and temozolomide (H3G34 mutation) (B) tovorafenib (MAPK pathway alterations), (D) olutasidenib and temozolomide (IDH1 mutation) [NCT06161974], (F) nivolumab and relatlimab (high tumor mutational burden, mismatch repair deficiency), (L) lorlatinib (+/- chemotherapy or radiation) (ROS1, ALK fusion). Development of additional treatment arms is underway, with possibility of incorporating new arms as supporting data allows."

Clinical • P2 data • Tumor mutational burden • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Pediatrics • Solid Tumor • ALK • IDH1 • ROS1 • TMB

Molecularly-guided phase 2 umbrella trial for children and young adults with newly-diagnosed high-grade glioma (HGG) including diffuse intrinsic pontine glioma (DIPG): CONNECT TarGeT (Targeted pediatric HGG therapy) trial in progress (SNO 2025) - P, P2 | "The following TarGeT treatment arms (most involving upfront radiotherapy), are open or soon to open, selected based on prevalence of targets in HGG/DIPG, relevant pre-clinical and clinical data, established pediatric safety data, and prioritizing combinations: (A) ribociclib and everolimus (target: cell cycle or PI3K//mTOR pathway alterations) [NCT05843253], (A-2) ribociclib and temozolomide (H3G34 mutation) (B) tovorafenib (MAPK pathway alterations), (D) olutasidenib and temozolomide (IDH1 mutation) [NCT06161974], (F) nivolumab and relatlimab (high tumor mutational burden, mismatch repair deficiency), (L) lorlatinib (+/- chemotherapy or radiation) (ROS1, ALK fusion). Development of additional treatment arms is underway, with possibility of incorporating new arms as supporting data allows."

Clinical • P2 data • Tumor mutational burden • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioma • High Grade Glioma • Pediatrics • Solid Tumor • ALK • IDH1 • ROS1 • TMB

Real-world outcomes in patients with brain metastases secondary to melanoma treated with nivolumab and relatlimab (SNO 2025) - "The combination of ipilimumab and nivolumab remains the standard of care for this patient population and there is limited data on the combination of nivolumab and relatlimab (nivo-rela) in MBM. The combination of nivo-rela showed intracranial activity in patients with MBM, particularly in the front-line setting. Prospective trials are needed to validate these findings and provide data on the optimal use of systemic and local therapies in this challenging patient population."

Clinical • Real-world • Real-world evidence • Melanoma • Solid Tumor

CONGRATS: A RANDOMIZED PHASE II STUDY OF NIVOLUMAB ± RELATLIMAB IN PATIENTS WITH TLS-POSITIVE ADVANCED SOFT-TISSUE SARCOMAS (CTOS 2025) - No abstract available

Clinical • Metastases • P2 data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

PROGRESSION FREE SURVIVAL OF IMMUNE CHECKPOINT INHIBITORS IN THE FIRST-LINE TREATMENT OF METASTATIC SARCOMA: A SINGLE CENTER RETROSPECTIVE ANALYSIS. (CTOS 2025) - "94% received pembrolizumab, 4% Nivolumab (3 with ipilimumab and 1 with relatlimab), and the remainder had trial enrolment. We present a real-world retrospective study in patients with sarcoma treated with first- line checkpoint inhibitor immunotherapy. The PFS was encouraging at 16.7 months, with an intriguing revelation of better survival in leiomyosarcoma numerically. Our results could be biased due to patient selection, but it remains an area of study that should be promoted."

Checkpoint inhibition • Metastases • Retrospective data • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor • PD-L1

International real-world study of combination immunotherapy sequences in metastatic melanoma. (PubMed, J Immunother Cancer) - "Our findings indicate that rela/nivo may remain active following anti-PD-1 or ipi/nivo therapy. Additionally, our results suggest that sequencing ipi/nivo before rela/nivo may yield better outcomes than starting with rela/nivo. Patients who respond to the first combination regimen appear to derive greater benefit from the second. Further efforts are needed to optimize sequencing strategies in advanced melanoma, and future studies should consider the impact of prior treatment outcomes."

Journal • Real-world evidence • Retrospective data • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • CTLA4 • LAG3

Real-world outcomes in patients with brain metastases secondary to melanoma treated with nivolumab and relatlimab (SNO 2025) - "The combination of ipilimumab and nivolumab remains the standard of care for this patient population and there is limited data on the combination of nivolumab and relatlimab (nivo-rela) in MBM. The combination of nivo-rela showed intracranial activity in patients with MBM, particularly in the front-line setting. Prospective trials are needed to validate these findings and provide data on the optimal use of systemic and local therapies in this challenging patient population."

Clinical • Real-world • Real-world evidence • Melanoma • Solid Tumor

Immunoediting in the melanoma tumor microenvironment (ESMO-IO 2025) - P1/2 | "We hypothesized that comparing TME sub-environments within a biopsy can reveal temporal changes of cancer immunoediting, also known as the paradigm of the "3 E's": Elimination, Equilibrium, and Escape.Methods Patients had localized melanoma treated with surgery and adjuvant nivolumab (cohort 1) or stage IV melanoma treated nivolumab and relatlimab on clinical trial in the second line (cohort 2). Those with a PR had fewer M2 macrophages (p=0.0485) compared to PD, in addition to more M1 macrophages, DCs, and B cells.Conclusions Our findings suggest that CTL density alone is insufficient for tumor regression. The spatial orientation of CTLs and their supporting cells, such as macrophages and DCs, play a key role.Clinical trial identification NCT01968109.Legal entity responsible for the study Svetomir Markovic, Bristol Myers Squibb."

Biomarker • IO biomarker • Tumor microenvironment • Melanoma • Oncology • Solid Tumor • MLANA • PD-1

Real-world experience of first-line nivolumab + relatlimab for advanced melanoma in Europe: focus on toxicity (ESMO-IO 2025) - "Background Ipilimumab and nivolumab is a standard first-line option in advanced melanoma but frequently causes immune-related adverse events (irAEs), which may be severe. Landmark OS was 63.7% at 12 months and 31.8% at 24 months.Conclusions In this large real-world cohort, first-line nivolumab and relatlimab achieved disease control and CR rates comparable to trial data, despite an older population and a higher prevalence of adverse prognostic factors such as BM and elevated LDH. Toxicity was substantial, with over one-third grade ≥3 events, frequent endocrine/cardiac irAEs, high steroid use, and treatment discontinuations, underscoring the need for optimised management in daily practice.Legal entity responsible for the study T. Peres."

Clinical • Metastases • Real-world • Real-world evidence • Endocrine Cancer • Melanoma • Oncology • Solid Tumor • BRAF

What Are the Likely PICOs for Tovorafenib and Lifileucel as the First Products to Go Through the JCA? (ISPOR-EU 2025) - "Based on the clinical trials of tovorafenib and lifileucel, predicting the PICOs in tovorafenib will be easier for the manufacturer than for lifileucel, primarily due to the lack of treatment options in LGG. The PICOs used in the tovorafenib trial are therefore closer to our predictions, however this study did not look at all member states, which is a limitation."

Brain Cancer • Glioma • Hematological Disorders • Melanoma • Pediatrics • Solid Tumor

Neo IRENIE (NEOadjuvant Ipilimumab, RElatlimab, NIvolumab Evaluation) (clinicaltrials.gov) - P2 | N=531 | Not yet recruiting | Sponsor: Melanoma Institute Australia | N=297 ➔ 531 | Initiation date: Sep 2025 ➔ Dec 2025 | Trial primary completion date: Sep 2027 ➔ Dec 2027

Enrollment change • IO biomarker • Trial initiation date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

Timing of initial immune checkpoint inhibitor administration and its impact on outcomes in metastatic melanoma (ESMO-IO 2025) - "Subgroup analyses were performed for pembrolizumab monotherapy and dual immunotherapy (ipilimumab/nivolumab and relatlimab/nivolumab).Results 218 patients met eligibility criteria; 80 received early and 138 late ICI administration. Three-year OS for dual immunotherapy with ipilimumab/nivolumab was 53.9% vs 61.7% (HR 0.97, p = 0.92) and with relatlimab/nivolumab was 77.1% vs 42.2% (HR 1.86, p = 0.92).Conclusions In patients with metastatic melanoma, clinical outcomes and treatment-related toxicities were comparable between early and late administration of immune checkpoint inhibitors. These results indicate that initial timing alone may have limited clinical significance; however, larger prospective studies are warranted to evaluate whether strategic scheduling could optimize immunotherapy efficacy.Legal entity responsible for the study The authors."

Checkpoint inhibition • Metastases • Melanoma • Oncology • Solid Tumor

Lead-in therapy targeting PD1 and/or LAG3 imposes distinct immune phenotypes in first-line treatment of metastatic melanoma. (PubMed, medRxiv) - P2 | "The analyses of component agents afforded by this novel lead-in trial has identified differential clinical and immunological modulation of anti-PD1 and anti-LAG3 in comparison to the combination therapy. Lead-in monotherapy with nivolumab or relatlimab reduces efficacy to the comboMPRbx serves as an early surrogate marker of response and long-term PFS Relatlimab lead-in led to CD8 + T cell:Treg clustering in the TME and poor PFS Combo therapy non-responders had decreased CD14 + CD16 - HLA-DR low CD33 dim monocytes."

IO biomarker • Journal • Immune Modulation • Immunology • Melanoma • Oncology • Solid Tumor • CD14 • CD33 • CD8 • FOXP3 • IFNG • LAG3

Combinatorial immune checkpoint blockade amplifies myocardial NLRP3 activation and elevates H-FABP, NT-proBNP, IL-1β and IL-6: Translational insights into cardio-immuno-oncology (ESMO-IO 2025) - "Recently, combinatorial strategies—such as the FDA-approved nivolumab + relatlimab (anti-LAG-3) in melanoma and ongoing trials of atezolizumab + ipilimumab in metastatic lung cancer—are expanding. Troponin-T, BNP, NT-Pro-BNP and H-FABP, were also strongly increased in combination therapy compared to monotherapy regimen. NLRP3 expression, IL-6 and IL-1β levels were also increased by PDL-1/CTLA-4 and PD-1/LAG-3 combined blocking agents.Conclusions Data of the present study, although in vitro, indicate that combinatorial immune checkpoint blockade, induce a pro- inflammatory phenotype, thus indicating that these therapies should be closely monitored by the multidisciplinary team consisting of oncologists, cardiologists and immunologists.Legal entity responsible for the study Istituto Nazionale Tumori-IRCCS- Fondazione G. Pascale of Naples, Italy."

Checkpoint block • Checkpoint inhibition • Immuno-oncology • IO biomarker • Lung Cancer • Melanoma • Oncology • Solid Tumor • HDAC4 • IL1B • IL6 • NDUFS1 • NLRP3

Opdualag vs. Cemiplimab/Fianlimab in Relation to the Immunological Response in Tumor and Peripheral Blood in Unresectable or Metastatic Melanoma (clinicaltrials.gov) - P=N/A | N=20 | Recruiting | Sponsor: John Kirkwood | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatocellular Cancer • Melanoma • Oncology • Solid Tumor

Real-world outcomes in patients with brain metastases secondary to melanoma treated with nivolumab and relatlimab (WFNOS 2025) - "The combination of ipilimumab and nivolumab remains the standard of care for this patient population and there is limited data on the combination of nivolumab and relatlimab (nivo-rela) in MBM. The combination of nivo-rela showed intracranial activity in patients with MBM, particularly in the front-line setting. Prospective trials are needed to validate these findings and provide data on the optimal use of systemic and local therapies in this challenging patient population."

Clinical • Real-world • Real-world evidence • Melanoma • Solid Tumor

Real-world outcomes in patients with brain metastases secondary to melanoma treated with nivolumab and relatlimab (WFNOS 2025) - "The combination of ipilimumab and nivolumab remains the standard of care for this patient population and there is limited data on the combination of nivolumab and relatlimab (nivo-rela) in MBM. The combination of nivo-rela showed intracranial activity in patients with MBM, particularly in the front-line setting. Prospective trials are needed to validate these findings and provide data on the optimal use of systemic and local therapies in this challenging patient population."

Clinical • Real-world • Real-world evidence • Melanoma • Solid Tumor

Early immunotherapy shows promising results in advanced basal cell carcinoma (Medical Xpress) - "Results from the phase 2 clinical trial (NCT03521830), presented Oct. 20 at the European Society for Medical Oncology (ESMO) annual meeting, show that first-line nivolumab, a PD-1 immune checkpoint inhibitor, produced an objective response rate (ORR) of 52% in 29 patients with inoperable BCC....Investigators also explored whether adding relatlimab, an anti–LAG-3 immune checkpoint inhibitor, to nivolumab could induce tumor regressions in patients whose disease had progressed on nivolumab alone. Among 13 such patients, the ORR was 31% (4 of 13)."

P2 data • Basal Cell Carcinoma

"AARON: Phase I/II Trial of Dual LAG-3/PD-1 Inhibition Combined With Azacitidine ± Venetoclax in AML – Interim Results" (DGHO 2025) - P2 | "2018). In the ongoing AARON trial (NCT04913922), we assess safety and efficacy of nivolumab (anti–PD-1, 480 mg) and relatlimab (anti–LAG-3, 160 mg) every 4 weeks in combination with AZA ± VEN (per standard of care) in AML. Combining AZA/VEN with LAG-3/PD-1 inhibition was safe and showed promising efficacy in adverse-risk frontline AML patients (per ELN 2022 criteria) ineligible for intensive chemotherapy. IrAEs were manageable and reversible. Patient recruitment and immunomonitoring to explore response mechanisms are ongoing."

P1/2 data • Acute Myelogenous Leukemia • Cardiovascular • Inflammation • Septic Shock • LAG3 • NPM1

Real-world Outcomes Among Patients With Melanoma Treated With Neoadjuvant Nivolumab+Relatlimab or Nivolumab+Ipilimumab (clinicaltrials.gov) - P=N/A | N=100 | Completed | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Completed

Real-world evidence • Trial completion • Melanoma • Oncology • Solid Tumor

Endoscopic Ultrasound With Fine Needle Biopsy Confirming a Diagnosis of Immune Checkpoint Inhibitor-Related Type 3 Autoimmune Pancreatitis. (PubMed, Case Rep Gastrointest Med) - "A 71-year-old male with metastatic mucosal melanoma of the urethra was treated with immune checkpoint inhibitor (ICI) therapy (nivolumab/relatlimab) and developed vague epigastric discomfort...He was treated successfully with prednisone...Type 3 AIP typically presents along with other immune-related adverse events. Endoscopic ultrasound with FNB contributed to diagnostic certainty in this case and changed our patient's management, allowing for appropriate treatment of his immune-related adverse event."

Checkpoint inhibition • Journal • Hodgkin Lymphoma • Immunology • Melanoma • Mucosal Melanoma • Oncology • Pancreatic Cancer • Pancreatitis • Solid Tumor • CD4 • CD8

Secondary Primary Lymphoma (SPL) Following Immune Checkpoint Inhibitor (ICI) Therapy: FDA Adverse Event Reporting System (FAERS) Review (SITC 2025) - "As clinical use expands, monitoring for emerging safety signals remains essential.Methods We searched the FAERS database for reports submitted through March 31, 2025, involving nivolumab, pembrolizumab, ipilimumab, atezolizumab, durvalumab, cemiplimab, avelumab, dostarlimab, and relatlimab/nivolumab. Other lymphomas reported include 6 Non-Hodgkin Lymphoma, 11 Metastatic Lymphoma, 3 Angiocentric Lymphoma, 1 Lymphoma Transformation. Death was reported in 32 cases.Conclusions This analysis identified SPL cases following ICI therapy including aggressive T-cell and B-cell lymphomas warranting further pharmacovigilance study as well as investigation of immune-mediated mechanisms of lymphomagenesis following ICI exposure."

Adverse events • Checkpoint inhibition • Review • Adult T-Cell Leukemia-Lymphoma • B Cell Lymphoma • Burkitt Lymphoma • CNS Lymphoma • Cutaneous T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Extranodal Marginal Zone Lymphoma • Follicular Lymphoma • Hematological Malignancies • Hepatosplenic T-cell Lymphoma • Indolent Lymphoma • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Small Lymphocytic Lymphoma • Solid Tumor • Splenic Marginal Zone Lymphoma • T Cell Non-Hodgkin Lymphoma • Waldenstrom Macroglobulinemia • LAG3 • PD-1

SUPRAME: A Phase 3 trial evaluating IMA203 PRAME-directed TCR T-cell therapy vs investigator's choice in previously treated advanced cutaneous melanoma (SITC 2025) - P1/2, P3 | "Patients in the control arm will receive nivolumab/relatlimab, nivolumab, ipilimumab, pembrolizumab, lifileucel (US), or chemotherapy. The trial is currently enrolling patients in the US and Germany and plans to enroll patients in France, the Netherlands, Canada, and the United Kingdom.Acknowledgements Study funding provided by Immatics US, Inc.Trial Registration NCT06743126Ethics Approval The protocol and all amendments were approved by the appropriate institutional review board or independent ethics committee at each participating study site. The study is being conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines."

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

Organ Preservation Approach with Upfront Dual Immune Checkpoint Inhibitors for Locally Advanced Mucosal Melanomas: A Case Series (SITC 2025) - "We report our experience with dual immune checkpoint inhibitors (ICIs) as an organ-preserving alternative approach.Methods Consecutive patients who started dual ICIs (ipilimumab and nivolumab or relatlimab and nivolumab) as initial therapy for locally advanced mucosal melanoma at Inova Schar Cancer Institute between 2017 and 2023 were retrospectively identified. A total of nine patients are alive up to date. Three experienced CTCAE grade 3 adverse events (pneumonitis, transaminase elevation).Conclusions Our case series demonstrates the potential of immunotherapy to achieve disease control while preserving organ function in patients with locally advanced mucosal melanoma."

Checkpoint inhibition • Clinical • Metastases • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor