OA11.04 Volrustomig + platinum doublet chemotherapy (CTx) in first-line non-small cell lung cancer (NSCLC): Phase 1b trial update
Recommended Citation
Spigel DR, Ahn M, Majem M, Medina Rodríguez L, Lee KH, Carcereny E, Hernández AA, Insa A, Cho EK, Besse B, Rha SY, Weiss J, D'Arcangelo M, Im S, Kim S, Carneiro BA, Gadgeel SM, Mitchell P, Asare JM, Gainer SD, Achour I, Subramaniam DS, Felip E. OA11.04 Volrustomig + platinum doublet chemotherapy (CTx) in first-line non-small cell lung cancer (NSCLC): Phase 1b trial update. J Thorac Oncol 2024; 19(10):S33-S34.
Document Type
Conference Proceeding
Publication Date
10-1-2024
Publication Title
J Thorac Oncol
Abstract
Introduction: Volrustomig, a novel PD-1/CTLA-4 bispecific antibody, has shown robust pharmacodynamic effect and clinical promise in multiple advanced solid tumors (Tran, AACR 2022; Albiges, ASCO 2022; Voss, ESMO 2023), and especially in PD-L1-negative first-line (1L) NSCLC (Ahn, ESMO 2022). PD-L1-negative NSCLC is a disease segment of key unmet need, with limited benefit gained from addition of anti-PD-(L)1 therapy alone to CTx, and where anti-PD-(L)1/anti-CTLA-4 therapy + CTx has previously shown clinical potential (Paz-Ares, Lancet Oncol 2021; Johnson, JCO 2023). Here we report updated results from patients with 1L advanced NSCLC treated with volrustomig 750mg + CTx in a global Phase 1b study. Methods: Patients with 1L advanced NSCLC were treated with volrustomig 750mg + CTx Q3W based on histology: 120 nonsquamous (Nsq) NSCLC patients enrolled over two different time periods (Cohort 1A: n=66; Cohort 1B: n=54) and 20 squamous (Sq) NSCLC patients (Cohort 2). The primary endpoint was objective response rate (ORR) in the Nsq cohorts and safety in the Sq cohort. Secondary endpoints included safety, tolerability, and disease control rate (DCR). Exploratory endpoints included receptor occupancy and pharmacodynamic biomarkers of CTLA-4 blockade. Results: Among 140 patients enrolled, 89 had PD-L1 tumor cell expression (TC) <1% NSCLC (63.6%), reflecting the unmet need and previously seen benefit of CTLA-4 inhibition in this population; median age was 68.0 years, 73.6% were males, 67.9% with ECOG performance status 1, 15.7% with liver metastases, and 15% with brain metastases. Efficacy outcomes are shown in the Table. Nearly all patients achieved disease control. Among evaluable patients with PD-L1 TC <1%, ORR in the Nsq (n=78) and Sq (n=10) cohorts was 42.3% and 50.0%, respectively. Median number of cycles was 6 (range 1-39); 97.1% and 75.7% of patients experienced all-grade and grade 3/4 treatment-related adverse events (AE), respectively. Seven treatment-related deaths occurred (two of which were volrustomig-related immune-related AEs): 6 in Cohort 1A, 0 in Cohort 1B, 1 in Cohort 2. Clinical peripheral T cell flow cytometry, TCR sequencing, and single-cell sequencing demonstrated greater T cell proliferation and memory T cell activation with volrustomig 750mg + CTx versus anti-PD1 + CTx. Conclusions: Volrustomig 750mg + CTx demonstrates robust PD-1/CTLA-4 blockade, manageable safety, and promising efficacy in 1L advanced NSCLC, especially in patients with PD-L1 TC <1%. The ongoing phase 3 EVOLVE-Lung02 trial (NCT05984277) is evaluating volrustomig + CTx for metastatic NSCLC with PD-L1 TC <50%. [Formula presented] Keywords: NSCLC, immunotherapy, chemotherapy
Volume
19
Issue
10
First Page
S33
Last Page
S34
