1187 Safety and efficacy of cesalatamig, a novel PD-1/VEGF bispecific antibody, as monotherapy in PD-(L)1–resistant/refractory NSCLC: Results from global, multicenter, open-label phase 1/2 studies
Year: 2026
Type: conference-abstract
Abstract: Background Patients with anti-PD-(L)1-resistant/refractory (R/R) non-small cell lung cancer (NSCLC) have limited treatment options other than chemotherapy. Cesalatamig is a novel PD-1/VEGF bispecific antibody with 40-fold higher affinity for VEGF than bevacizumab. As a result, cesalatamig showed best-in-class potential with a differentiated cooperative interaction that favor its action in a PD-1 and VEGF-rich tumor microenvironment. Cesalatamig also has more effective Fc-silencing modifications to avoid the depletion of PD-1 positive effector T cells. Here we report the preliminary safety and clinical activity of cesalatamig in pretreated patients with NSCLC from the global Phase 1/2 studies.Methods In these global, multicenter, open-label Phase 1/2 studies, a total of 103 patients with NSCLC from US and China, who experienced disease progression after ≥1 line of systemic therapy were enrolled to receive cesalatamig monotherapy at 1, 3, 10 and 20 mg/kg, Q3W, and were included in the safety population. As of July 31, 2026, 55 anti-PD(L)1-R/R patients have received at least one post-baseline tumor assessment per RECIST 1.1. Clinical activity was evaluated by investigator-determined objective response rate (ORR) and disease control rate (DCR).Results The safety population included 103 patients with NSCLC, with 77 (75%) non-squamous and 25 (24%) with squamous and one unknown histology ( table 1). 77% of patients had a baseline ECOG score of 1. The median number of prior lines of therapy was 2, while 42% of patients had received 3+ prior lines, including both standard of care chemotherapies and immunotherapies. Grade 3-4 treatment-related adverse events (TRAEs) were seen in 18%, while treatment-related serious adverse events were observed in 11% of patients. The safety profile in squamous and non-squamous histology was comparable. The most common Grade 3-4 TRAE was hypertension (10%). Treatment related drug discontinuation was 1%. Of the 55 evaluable patients (figure 1), 10, 24 and 21 patients received 1, 3 and 10 mg/kg of cesalatamig, respectively. The ORR was 10%, 21%, and 33%, respectively, while the DCR was 40%, 67%, and 90%, respectively. Patients with NSCLC demonstrated disease response to cesalatamig monotherapy regardless of PD-L1 level. Exposure-response analyses support selection of 10 mg/kg Q3W as the dose for a pivotal study in planning.Conclusions Cesalatamig monotherapy demonstrated robust and clinically meaningful antitumor activity with a manageable safety profile in patients with PD-(L)1-R/R NSCLC. To our knowledge this is the first report of global Phase 2 results that support pivotal trial using dual PD-1/VEGF blockade in this indication.Acknowledgements The authors would like to thank the patients and their families/caregivers, the staff, research coordinators, and investigators at each participating institution. Medical writing assistance was provided by Drs. Chris Leung, Juan Su, and David Cerna from OncoC4 in accordance with the Good Publication Practice guidelines.Trial Registration The BiPAVE-001 trials are registered as NCT06635785 in the U.S. and registered as CTR20253261 in China.Ethics Approval The BiPAVE-001 trials are being conducted under WCG IRB Study Number 20244932 and registered as NCT06635785 in the U.S., and under Guangdong Provincial People’s Hospital’s EC Number YW2025-087 and registered as CTR20253261 in China.Abstract 1187 Figure 1Waterfall plot of prior PD-(L)1 inhibitor experienced, AGA negative NSCLC treated with cesalatamig Q3WAbstract 1187 Table 1Summary of demographics, patient characteristic and safety results
Authors: Kai He, Jin-ji Yang, Mingjia Li, Maya Khalil, Vaia Florou, Matthrew Gumbleton, Bin Yang, Zhi-hua Liu, Luis Raez, Eric Schaefer, Cameron Pywell, Joshua Reuss, Yu Liu, John Hamm, Qitao Yu, Huilin Wang, Guru P Sonpavde, Tarek Mekhail, Stephane Champiat, Devalingam Mahalingam, Bilal Anouti, Yongsheng Li, Meili Sun, Qing Wen, Thomas J George, Aline Fares, Fawzi Abu Rous, Georgios Fotopoulos, Shiling Song, Kazuharu Kai, Kun He, Yang Liu, Pan Zheng, Yi-Long Wu
Institutions: Mays Cancer Center at UT Health San Antonio, Guangdong Provincial People's Hospital, The Ohio State University, University of Alabama at Birmingham, Huntsman Cancer Institute, Hubei Cancer Hospital, Jiangxi Provincial Cancer Hospital, Memorial Healthcare System, Highlands Oncology Group, Novant Health, Georgetown Lombardi Comprehensive Cancer Center, Norton Healthcare, Guangxi Medical University, Tumor Hospital of Guangxi Medical University, AdventHealth, The University of Texas MD Anderson Cancer Center, Northwestern University, Chongqing University, Chongqing Cancer Hospital, Jinan Central Hospital, University of Florida, Henry Ford Health
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225433566