A randomized phase 3 study of ivonescimab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of metastatic non–small cell lung cancer: HARMONi-3.
Year: 2025
Type: conference-abstract
Abstract: TPS8664 Background: The additionof antiangiogenic agents to standard first-line treatment with a programmed cell death protein 1 (PD-1) inhibitor and platinum doublet chemotherapy has shown efficacy in patients with metastatic non–small cell lung cancer (NSCLC). Ivonescimab is a novel tetravalent bispecific antibody that targets PD-1 and vascular endothelial growth factor. In a phase 2 trial, ivonescimab plus chemotherapy showed objective response rates (ORRs) of 71.4% and 54.2% and median progression-free survival (PFS) of 11.1 and 13.3 months in patients with metastatic squamous (SQ) and nonsquamous (NSQ) NSCLC, respectively (1). Methods: The multiregional, randomized, double-blind, phase 3 HARMONi-3 trial (NCT05899608) will compare the efficacy and tolerability of ivonescimab plus chemotherapy with pembrolizumab plus chemotherapy as first-line treatment in patients with metastatic SQ or NSQ NSCLC who have not previously received systemic treatment for metastatic disease and whose tumors have no known actionable mutations for which approved first-line therapies are available. Patients will be randomly assigned (1:1) to receive ivonescimab 20 mg/kg every 3 weeks (Q3W) or pembrolizumab 200 mg Q3W combined with chemotherapy (paclitaxel or nab-paclitaxel plus carboplatin for SQ or pemetrexed plus carboplatin for NSQ) for up to 4 cycles, followed by maintenance with ivonescimab or pembrolizumab alone for SQ or in combination with pemetrexed for NSQ for up to 24 months. Randomization will be done in blocks by histology (SQ and NSQ) and stratified by sex (female vs male), age (<65 vs ≥65 y), geographic region (East Asia vs rest of world), presence or absence of liver or brain metastases at baseline, previous PD-1 or programmed death ligand 1 (PD-L1) inhibitor treatment >6 months before the development of metastatic disease (yes vs no), and PD-L1 tumor proportion score (≥1% or <1%). The dual primary end points are overall survival and PFS (assessed by investigators per RECIST v1.1). The secondary end points are ORR, disease control rate, duration of response, safety, pharmacokinetics, and immunogenicity. Patients are being recruited in Asia, Europe, and North America, with a target enrollment of 1080 patients (45-50% SQ and 50-55% NSQ). 1. Zhang L et al, ELCC 2024, FPN: 68P. Clinical trial information: NCT05899608 .
Source: Journal of Clinical Oncology
Authors: Jianjun Zhang, Jun Cai, Hui Wang, Yan Yu, Joaquim Bosch-Barrera, Reyes Bernabé, Zoran Andric, Firas Benyamine Badin, Yusuke Okuma, Paul K. Paik, Jarushka Naidoo, Haralabos Kalofonos, Bo Wang, Robert M. Jotte, Nathan A. Pennell, Jonathan W. Riess, Deborah Blythe Doroshow, Makoto Nishio, Jorge Arturo Alatorre-Alexander, Shun Lu
Institutions: The University of Texas MD Anderson Cancer Center, Yangtze University, Central South University, Hunan Cancer Hospital, Harbin Medical University, Third Affiliated Hospital of Harbin Medical University, Institut Català d'Oncologia, Hospital Universitari de Girona Doctor Josep Trueta, Hospital Universitario Virgen del Rocío, University Hospital Medical Center Bezanijska kosa, Central Baptist Hospital, National Cancer Center Hospital, Memorial Sloan Kettering Cancer Center, Royal College of Surgeons in Ireland, Beaumont Hospital, Patras Olympian Hospital, Willamette Valley Cancer Institute and Research Center, Rocky Mountain Cancer Centers, Cleveland Clinic, UC Davis Comprehensive Cancer Center, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, The Cancer Institute Hospital, Japanese Foundation For Cancer Research, Shanghai Jiao Tong University, Shanghai Chest Hospital
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410804525