relatlimab (BMS-986016)

P2, N=385, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Feb 2024 --> Jun 2024 | Trial primary completion date: Feb 2024 --> Jun 2024

P2, N=0, Withdrawn, National Cancer Institute (NCI)

P2, N=59, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: May 2024 --> Feb 2024

P1, N=33, Not yet recruiting, Washington University School of Medicine | Trial completion date: Mar 2030 --> Jun 2030 | Trial primary completion date: Jun 2028 --> Sep 2028

Here, we report a case of an 89-year-old patient with metastatic melanoma to the liver, lung and lymph nodes, who underwent treatment with Opdualag (combining anti-PD-1 nivolumab and anti-lymphocyte-activation gene 3 relatlimab ICBs), and developed pseudoprogression after two cycles of therapy. The patient experienced a radiographic increase in liver metastatic lesion size, but was found to have a subsequent reduction in these lesions. The patient has been on therapy for 18 months without evidence of disease progression and continues to be clinically well-appearing.

P2, N=10, Completed, Jonsson Comprehensive Cancer Center | Active, not recruiting --> Completed | Trial completion date: Apr 2025 --> Sep 2023 | Trial primary completion date: Apr 2024 --> Sep 2023

"Natera, Inc...today announced the launch of Alliance A032103 (MODERN), a randomized, phase II/III, biomarker-integrated trial. Alliance A032103 (MODERN) will utilize Signatera, Natera’s personalized and tumor-informed molecular residual disease (MRD) test, to help guide personalized treatment based on molecular status in patients diagnosed with muscle-invasive urothelial cancer (MIUC) after radical cystectomy....In the Alliance A032103 (MODERN) trial, approximately 1,000 patients will be enrolled at more than 300 sites in North America. Patients will be divided into two cohorts based on an initial assessment of MRD status. Patients who are Signatera MRD-positive will have treatment randomized to either nivolumab, a PD-1 antibody, or escalation with nivolumab, a PD-1 antibody plus relatlimab, a LAG-3 antibody; LAG-3 and PD-1 are distinct inhibitory immune checkpoints."

He continued to show no evidence of disease at recent follow-up. Treatment of metastatic melanoma of the skin with nivolumab and relatlimab is an effective approach showing greater benefit to patients than nivolumab alone.

P2, N=178, Not yet recruiting, National Cancer Institute (NCI)

P2, N=57, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Nov 2027 --> Mar 2027 | Trial primary completion date: Nov 2024 --> Mar 2026

P1, N=1, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | N=24 --> 1

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 .

P2, N=59, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting | N=96 --> 59 | Trial primary completion date: Feb 2025 --> May 2024

P3; Phase classification: P2/3 --> P3

P2, N=266, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Jan 2025 --> Sep 2024

P2; Not yet recruiting --> Recruiting

P1, N=30, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Not yet recruiting --> Recruiting

P1, N=30, Not yet recruiting, H. Lee Moffitt Cancer Center and Research Institute

P2, N=20, Not yet recruiting, Melanoma Institute Australia

P2, N=90, Recruiting, The Netherlands Cancer Institute | Not yet recruiting --> Recruiting

P1, N=6, Completed, Bristol-Myers Squibb | Recruiting --> Completed | N=12 --> 6 | Trial completion date: Nov 2025 --> Jan 2024 | Trial primary completion date: Nov 2025 --> Jan 2024

P3, N=680, Recruiting, Immunocore Ltd | Not yet recruiting --> Recruiting

P3, N=400, Not yet recruiting, Replimune Inc.

P2/3; Initiation date: Oct 2024 --> Feb 2024

P2, N=96, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

P1, N=35, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Sep 2023 --> Jul 2025 | Trial primary completion date: Sep 2023 --> Jul 2024

P1/2, N=1499, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Aug 2026 --> Sep 2024

P3, N=560, Not yet recruiting, Regeneron Pharmaceuticals

P2, N=90, Not yet recruiting, The Netherlands Cancer Institute

After pCSI with concurrent nivolumab, the addition of relatlimab, and BRAF-targeted therapy, he remained alive 7 months after LMD diagnosis despite central nervous system progression...He received pCSI with concurrent ipilimumab and nivolumab, then nivolumab maintenance...Adding an ICI to pCSI is feasible for patients with LMD and demonstrates a tolerable toxicity profile. While prospective evaluation is ultimately warranted, pCSI with ICI may confer survival benefits, even after prior ICI.

Monoclonal antibodies against CTLA-4 or PD-1 or PDL-1 are the most studied ICIs in randomized clinical trials, however, more recently, an anti-LAG3 (Lymphocyte activation gene-3) antibody, Relatlimab, has been approved by FDA in combination with Nivolumab for metastatic melanoma therapy. Moreover, Atezolizumab is actually under study in association with Ipilimumab for therapy of metastatic lung cancer...NLRP3 expression, IL-6 and IL-1β levels were also increased by PDL-1/CTLA-4 and PD-1/LAG-3 combined blocking agents compared to untreated cells and monotherapies. 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.

P2, N=20, Active, not recruiting, Dan Zandberg | Recruiting --> Active, not recruiting

Ipilimumab plus nivolumab has achieved the best median overall survival, exceeding 70 months. However, the introduction of new ICIs, like relatlimab, has added complexity to first-line therapy decisions...We also provide the latest insights into the treatment of rare melanoma subtypes, such as uveal melanoma, where tebentafusp has shown promising improvements in overall survival for metastatic uveal melanoma patients. This review provides invaluable insights for clinicians, enabling informed treatment choices and deepening our understanding of the multifaceted challenges associated with advanced melanoma management.

On 18 March 2022, the U.S. FDA approved the fixed-dose combination of relatlimab developed by Bristol Myers Squibb with nivolumab, under the brand name Opdualag for the treatment of unresectable or metastatic melanoma in adult and pediatric patients aged 12 and older. This study comprehensively describes the mechanism of action and clinical trials of relatlimab and a brief overview of immune checkpoint drugs currently used for the treatment of melanoma.

P2, N=156, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Initiation date: Feb 2024 --> Oct 2024

P2/3; Not yet recruiting --> Recruiting | Initiation date: Jan 2024 --> Oct 2024

P1, N=32, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Jan 2024 --> Sep 2024

P1/2, N=21, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=80, Recruiting, Robert L. Ferris, MD, PhD | Trial completion date: Jul 2025 --> Sep 2027 | Trial primary completion date: May 2025 --> May 2027

These new plethora of options pose new challenges not only for optimal treatment sequencing strategies but especially for management of adverse effects, endorsing the need to integrate a holistic and personalized approach for patient care.

P1, N=80, Active, not recruiting, TriSalus Life Sciences, Inc. | Recruiting --> Active, not recruiting

Additionally, we present a patient with locally-advanced BCC who experienced stable disease during and after 45 weeks of first-line anti-PD-1 (nivolumab), followed by a partial response after the addition of anti-LAG-3 (relatlimab). Longitudinal biopsies throughout the treatment course showed a graduated increase in LAG-3 expression after anti-PD-1 therapy, lending support for coordinated immunosuppression and suggesting LAG-3 as a co-target for combination therapy to augment the clinical impact of anti-PD-(L)1.