KN046, a bispecific antibody against PD-L1 and CTLA-4, plus chemotherapy as first-line treatment for metastatic NSCLC: A multicenter phase 2 trial

• Published in: Cell reports. Medicine 2024-03, Vol.5 (3), p.101470-101470, Article 101470
• Main Authors: Zhao, Yuanyuan, Chen, Gang, Li, Xingya, Wu, Jingxun, Chang, Baoping, Hu, Sheng, Yang, Shujun, Xu, Ting, Liu, Yilan, Wang, Ni, Zhang, Li, Huang, Yan
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents - therapeutic use; B7-H1 Antigen; bispecific antibody; Carcinoma, Non-Small-Cell Lung - pathology; chemotherapy; CTLA-4 Antigen; cytotoxic T lymphocyte-associated antigen-4; first-line; Humans; KN046; Lung Neoplasms - pathology; non-small cell lung cancer; Pemetrexed - therapeutic use; programmed cell death-ligand 1
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2024.101470

KN046, a bispecific antibody targeting PD-L1 and CTLA-4, presents a promising therapeutic option for metastatic non-small cell lung cancer (NSCLC). In this multicenter phase 2 trial, patients with nonsquamous (non-sq) NSCLC receive pemetrexed, whereas those with sq-NSCLC receive paclitaxel, plus KN046 and carboplatin. Following four cycles, maintenance therapy includes KN046 with pemetrexed for non-sq-NSCLC and KN046 for sq-NSCLC. The objective response rate is 46.0%, and the median duration of response is 8.1 months. The median progression-free and overall survival are 5.8 and 26.6 months, respectively. The common adverse events include anemia (87.4%), loss of appetite (72.4%), and neutropenia (70.1%). The most prevalent immune-related adverse event is pruritus (28.7%). These findings indicate that first-line treatment with KN046 and chemotherapy is effective and tolerable in metastatic NSCLC patients, warranting further investigation in a larger phase 3 trial. The trial is registered at ClinicalTrials.gov (NCT04054531). [Display omitted] •KN046 is a bispecific antibody targeting PD-L1 and CTLA-4•First-line KN046 plus chemotherapy shows promise in metastatic NSCLC•The treatment regimen is well tolerated, with manageable side effects•A large-scale randomized phase 3 trial is ongoing to verify these findings Zhao et al. reveal that KN046, targeting PD-L1 and CTLA-4, combined with chemotherapy, shows notable efficacy in first-line treatment of metastatic NSCLC with manageable side effects. A phase 3 trial is underway to confirm these results.