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

Memory-Like Natural Killer Cells With Nivolumab and Relatlimab in Advanced or Metastatic Melanoma After Progression on Checkpoint Inhibitors (clinicaltrials.gov) - P1 | N=33 | Recruiting | Sponsor: Washington University School of Medicine | Suspended ➔ Recruiting

Checkpoint inhibition • Enrollment open • Melanoma • Oncology • Solid Tumor • PD-L1

Memory-Like Natural Killer Cells With Nivolumab and Relatlimab in Advanced or Metastatic Melanoma After Progression on Checkpoint Inhibitors (clinicaltrials.gov) - P1 | N=33 | Not yet recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Sep 2029 ➔ Mar 2030 | Initiation date: Sep 2023 ➔ Mar 2024 | Trial primary completion date: Dec 2027 ➔ Jun 2028

Checkpoint inhibition • Trial completion date • Trial initiation date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • PD-L1

Memory-Like Natural Killer Cells With Nivolumab and Relatlimab in Advanced or Metastatic Melanoma After Progression on Checkpoint Inhibitors (clinicaltrials.gov) - P1 | N=33 | Not yet recruiting | Sponsor: Washington University School of Medicine

Checkpoint inhibition • New P1 trial • Melanoma • Oncology • Solid Tumor • PD-L1

Memory-Like Natural Killer Cells With Nivolumab and Relatlimab in Advanced or Metastatic Melanoma After Progression on Checkpoint Inhibitors (clinicaltrials.gov) - P1 | N=33 | Not yet recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Jun 2029 ➔ Sep 2029 | Initiation date: Jun 2023 ➔ Sep 2023 | Trial primary completion date: Sep 2027 ➔ Dec 2027

Checkpoint inhibition • Trial completion date • Trial initiation date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • PD-L1

Memory-Like Natural Killer Cells With Nivolumab and Relatlimab in Advanced or Metastatic Melanoma After Progression on Checkpoint Inhibitors (clinicaltrials.gov) - P1 | N=33 | Not yet recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Feb 2029 ➔ Jun 2029 | Initiation date: Feb 2023 ➔ Jun 2023 | Trial primary completion date: May 2027 ➔ Sep 2027

Checkpoint inhibition • Trial completion date • Trial initiation date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • PD-L1

Memory-Like Natural Killer Cells With Nivolumab and Relatlimab in Advanced or Metastatic Melanoma After Progression on Checkpoint Inhibitors (clinicaltrials.gov) - P1 | N=33 | Not yet recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Mar 2030 ➔ Jun 2030 | Trial primary completion date: Jun 2028 ➔ Sep 2028

Checkpoint inhibition • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • PD-L1

Memory-Like Natural Killer Cells With Nivolumab and Relatlimab in Advanced or Metastatic Melanoma After Progression on Checkpoint Inhibitors (clinicaltrials.gov) - P1 | N=33 | Recruiting | Sponsor: Washington University School of Medicine | Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Enrollment open • Melanoma • Oncology • Solid Tumor • PD-L1

Memory-Like Natural Killer Cells With Nivolumab and Relatlimab in Advanced or Metastatic Melanoma After Progression on Checkpoint Inhibitors (clinicaltrials.gov) - P1 | N=33 | Suspended | Sponsor: Washington University School of Medicine | Recruiting ➔ Suspended

Checkpoint inhibition • Trial suspension • Melanoma • Oncology • Solid Tumor • PD-L1

TRIPLE M SYNDROME AFTER FIRST-DOSE OPDUALAG: SEVERE MULTISYSTEM IMMUNE TOXICITY WITH DUAL PD-1/LAG-3 BLOCKADE (CHEST 2026) - "Although various ICIs such as pembrolizumab, nivolumab, durvalumab, and other PD-1/PD-L1 inhibitors have been associated with TMOS case reports and small series, to date there are no well-documented reports of TMOS specifically attributed to Opdualag (nivolumab + relatlimab), a PD-1 and LAG-3 blocking combination approved for advanced melanoma. This case highlights the potential for Opdualag to precipitate life-threatening Triple-M syndrome in patients with metastatic melanoma, expanding the spectrum of ICI-related toxicity beyond isolated organ dysfunction to include severe multisystem irAEs. Clinicians should maintain a high index of suspicion for TMOS in patients on Opdualag presenting with cardiopulmonary and neuromuscular symptoms soon after initiation. Early recognition, discontinuation of ICI therapy, and aggressive immunomodulatory therapy are essential but may not alter the high mortality associated with TMOS."

Acute Coronary Syndrome • Cardiovascular • Chronic Obstructive Pulmonary Disease • CNS Disorders • Cognitive Disorders • Coronary Artery Disease • Diabetes • Heart Failure • Hypertension • Immunology • Melanoma • Metabolic Disorders • Myasthenia Gravis • Myocardial Infarction • Myositis • Oncology • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • LAG3

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Iovance Biotherapeutics, Inc.

New P2 trial • Melanoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ALK • ROS1

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • 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 • Thoracic Cancer • ALK • ROS1

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | N=36 ➔ 48

Enrollment change • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • ALK • ROS1

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=75 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | N=48 ➔ 75

Enrollment change • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • ALK • ROS1

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=135 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | N=75 ➔ 135

Enrollment change • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • ALK • ROS1

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=178 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | N=135 ➔ 178

Enrollment change • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • ALK • ROS1

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=178 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | Trial completion date: Dec 2024 ➔ Aug 2029 | Trial primary completion date: Dec 2023 ➔ Aug 2029

Trial completion date • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • ALK • ROS1

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 of Head and Neck • ALK • ROS1

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=225 | Terminated | Sponsor: Iovance Biotherapeutics, Inc. | Trial completion date: Aug 2029 ➔ Feb 2026 | Recruiting ➔ Terminated | Trial primary completion date: Aug 2029 ➔ Feb 2026; After reviewing the available safety and efficacy data to date, Iovance concluded that the study reached the required number of events for evaluation of study endpoints.

Trial completion date • Trial primary completion date • Trial termination • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • ALK • ROS1

CA224-1065: Neoadjuvant Nivolumab and Relatlimab in Cutaneous Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Melanoma Institute Australia

New P2 trial • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

CA224-1065: Neoadjuvant Nivolumab and Relatlimab in Cutaneous Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Melanoma Institute Australia | Trial completion date: Apr 2036 ➔ Jul 2036 | Initiation date: Apr 2024 ➔ Jul 2024 | Trial primary completion date: Jun 2026 ➔ Sep 2026

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

CA224-1065: Neoadjuvant Nivolumab and Relatlimab in Cutaneous Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Melanoma Institute Australia | Not yet recruiting ➔ Recruiting

Enrollment open • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Beyond Hepatocytes: Recognizing ICI Cholangitis in the Era of Combination Immunotherapy (ACG 2026) - "Case Description/ A 46-year-old woman with recurrent BRAF V600-positive metastatic melanoma, refractory to targeted therapy and pembrolizumab, was escalated to nivolumab/relatlimab...ICI-related hepatitis was suspected; immunotherapy was held, and prednisone 1mg/kg/day initiated...Adjunctive budesonide led to transient improvement, but taper attempts triggered relapse...Despite normalization of transaminases by October, ALP remained persistently elevated (441 U/L), consistent with bile duct-predominant injury. Abbreviations: CT, computed tomography; MMF, mycophenolate mofetil; UDCA, ursodeoxycholic acid; MRCP, magnetic resonance cholangiopancreatography; SC, sclerosing cholangitis."

Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Liver Failure • Melanoma • Solid Tumor • BRAF • CD8 • LAG3

ClearMe: Clear Me: Interception Trial to Detect and Clear Molecular Residual Disease in Patients With High-risk Melanoma (clinicaltrials.gov) - P2 | N=54 | Recruiting | Sponsor: University Health Network, Toronto

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

Switching Lanes: Successful PD-1/LAG-3 Rechallenge After Infliximab-Requiring ICI-Colitis From PD-1/CTLA-4 in Perianal Melanoma (ACG 2026) - "Introduction: ICI-colitis occurs in up to 25% of patients on nivolumab/ipilimumab and can be treatment-limiting...Prednisone 100 mg daily was initiated with improvement, but she could not taper below 5 mg without symptom recurrence...Despite this, she tolerated rechallenge without GI toxicity. This case supports nivolumab/relatlimab as a viable rechallenge option after severe ICI-colitis and highlights the role of GI-oncology collaboration in these decisions."

Gastroenterology • Gastrointestinal Disorder • Immunology • Melanoma • Solid Tumor • CTLA4 • LAG3 • PD-1

ClearMe: Clear Me: Interception Trial to Detect and Clear Molecular Residual Disease in Patients With High-risk Melanoma (clinicaltrials.gov) - P2 | N=54 | Recruiting | Sponsor: University Health Network, Toronto | Initiation date: May 2024 ➔ Jul 2024

Trial initiation date • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor