RELATIVITY-104 Part 2: translational analyses in the programmed death ligand 1 (PD-L1) ≥ 1% and non-squamous (NSQ) non-small cell lung cancer (NSCLC) subgroup
Presenter: Jaclyn Neely, PhD Session: Late-Breaking Research: Clinical Research 4 Time: 4/22/2026 9:00:00 AM → 4/22/2026 12:00:00 PM
Authors
Jaclyn Neely 1 , Annie Yu 1 , Nicolas Girard 2 , Manuel Cobo-Dols 3 , Mauricio Burotto 4 , Luis Paz-Ares 5 , Vamsidhar Velcheti 6 , Martin Reck 7 , Srijata Samanta 1 , Anila Qureshi 1 , Priyanka Kasbekar 1 , Charlie Garnett-Benson 1 1 Bristol Myers Squibb, Princeton, NJ, 2 Institut du Thorax Curie-Montsouris, Institut Curie, Paris, France, 3 Hospital Regional Universitario de Málaga, Malaga, Spain, 4 Bradford Hill Centro de Investigaci ón Clínica, Santiago, Chile, 5 Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain, 6 Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL, 7 Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany
Abstract
Background: In Part 2 of the phase 2 RELATIVITY-104 study of first-line nivolumab (NIVO) plus relatlimab (RELA) with platinum-doublet chemotherapy (PDCT) vs NIVO + PDCT in patients with metastatic NSCLC, NIVO + RELA + PDCT demonstrated improved clinical benefit, including overall survival, in the prespecified subgroup of tumor PD-L1 expression ≥ 1%, which was further enriched in NSQ tumor histology. Baseline lymphocyte-activation gene 3 (LAG-3) expression was associated with enriched efficacy for both NIVO + RELA + PDCT and NIVO + PDCT. In a comparative transcriptomic analysis, NSQ and squamous tumors demonstrated distinct immune signatures, with NSQ tumors exhibiting higher expression of LAG-3 ligands and greater enrichment for combination therapy benefit by PD-L1 expression. To further elucidate the mechanism of action of NIVO + RELA + PDCT, we report additional exploratory translational data in the PD-L1 ≥ 1% NSQ subgroup for Part 2 of RELATIVITY-104. Methods: Patients with untreated metastatic NSCLC were randomized 1:1 to NIVO 360 mg + RELA 360 mg + PDCT or NIVO 360 mg + PDCT Q3W. Exploratory endpoints included translational analyses in the PD-L1 ≥ 1% NSQ subgroup. Gene expression data from pretreatment tumor RNA sequencing were normalized and analyzed for associations with clinical outcomes. Pre- and on-treatment peripheral blood samples were collected for high-dimensional flow cytometry immunophenotyping using a validated 24-marker LAG-3-specific panel that used drug-tolerant, noncompeting clones for LAG-3, PD-1, and CTLA-4. Statistical associations between biomarkers and clinical outcomes were assessed using logistic regression and Cox proportional hazards models. Data are from the May 2, 2025, database lock. Results: In the NIVO + RELA + PDCT arm, immune signatures demonstrated a significantly lower hazard ratio (HR) in the PD-L1 ≥ 1% NSQ subgroup, while stromal signatures demonstrated a significantly higher HR. T exhausted progenitor signature subsets, as well as ICOS+ CD4+ T cells, at baseline were shown to enrich for survival with NIVO + RELA + PDCT. Clinical benefit was observed across all baseline LAG-3 expression levels ( Conclusions: In the RELATIVITY-104 study, the on-treatment immune dynamics of LAG-3+ T cells correlated with the benefit of NIVO + RELA + PDCT vs NIVO + PDCT in patients with PD-L1 expression ≥ 1% and NSQ NSCLC. Immune signatures including progenitor T exhausted signatures associated with improved outcomes with NIVO + RELA + PDCT. These data support the mechanistic rationale for adding anti-LAG-3 to anti-PD-1 + PDCT in PD-L1 ≥ 1% NSQ NSCLC.
Disclosure
J. Neely, Bristol Myers Squibb Employment, Stock. A. Yu, Bristol Myers Squibb Employment, Stock. N. Girard, None.. M. Cobo-Dols, None.. M. Burotto, None. L. Paz-Ares, MSD Other, Grants or contracts, consulting fees. AstraZeneca Other, Grants or contracts, consulting fees, and payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events. Pfizer Other, Grants or contracts, consulting fees. BMS Other, Grants or contracts, consulting fees. Lilly Other, Consulting fees. Roche Other, Consulting fees. PharmaMar Other, Consulting fees. Merck Other, Consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events. Novartis Other, Consulting fees. Servier Other, Consulting fees. Bayer Other, Consulting fees. Amgen Other, Consulting fees. Sanofi Other, Consulting fees. Mirati Other, Consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events. GSK Other, Consulting fees. Janssen Other, Consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events. Takeda Other, Consulting fees. Daichii Sankyo Other, Consulting fees. V. Velcheti, BMS, Merck, Astrazenca, BI Oncology, Abbott Independent Contractor, Other, Consulting, Advisory Role. M. Reck, Amgen Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and support for attending meetings and/or travel. AstraZeneca Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and support for attending meetings and/or travel. Beigene Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and support for attending meetings and/or travel. Boehringer-Ingelheim Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and support for attending meetings and/or travel. BMS Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and support for attending meetings and/or travel. Lilly Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and support for attending meetings and/or travel. Merck Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and support for attending meetings and/or travel. MSD Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and support for attending meetings and/or travel. Mirati Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and support for attending meetings and/or travel. Novartis Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and support for attending meetings and/or travel. GSK Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and support for attending meetings and/or travel. Pfizer Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and support for attending meetings and/or travel. Roche Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and support for attending meetings and/or travel. Regeneron Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and support for attending meetings and/or travel. Sanofi Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; support for attending meetings and/or travel; and participation on a data safety monitoring board or advisory board. Daiichi-Sankyo Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; support for attending meetings and/or travel; and participation on a data safety monitoring board or advisory board. Janssen Other, Consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and support for attending meetings and/or travel. S. Samanta, Bristol Myers Squibb Employment. A. Qureshi, Bristol Myers Squibb Company Employment. P. Kasbekar, Bristol Myers Squibb Employment. C. Garnett-Benson, Bristol Myers Squibb Employment, Stock.
Cited in
Control: 11163 · Presentation Id: 11390 · Meeting 21436