Abstract LB473: JNJ-95437446: Discovery and preclinical characterization of an amivantamab-based EGFR/MET-ADC for solid tumor indications

Abstract JNJ-95437446 is a potential best-in-class EGFR/MET bispecific antibody drug conjugate designed to deliver a cytotoxic payload to tumor cells while leveraging the unique characteristics of amivantamab. EGFR and MET are frequently expressed in solid tumors and amivantamab has demonstrated clinical efficacy in multiple non-small cell lung cancer (NSCLC) indications and is being studied in colorectal and head & neck carcinomas. Therefore, to assess the unique characteristics of JNJ-95437446, the ADC was evaluated in preclinical models of these tumor types. JNJ-95437446 uses a dual-maleimide linker-payload CPT-113 (Hangzhou DAC Biotechnology Co., Ltd.) to retain antibody stability upon conjugation. Preclinical experiments demonstrated JNJ-95437446 retained amivantamab-like binding to EGFR and MET, induced rapid internalization, and produced potent, target-dependent cytotoxicity in vitro. Additionally, the released payload from the ADC was capable of bystander cytotoxicity. JNJ-95437446 resulted in potent efficacy, including complete tumor regressions, in preclinical cell line-derived NSCLC xenograft models of adenocarcinoma and squamous cell carcinoma, and in models resistant to amivantamab. In multi-dose GLP NHP safety assessment studies, JNJ-95437446 was well tolerated at all doses tested and pharmacokinetic analysis demonstrated favorable linker/payload stability. JNJ-95437446 is an EGFR/MET-ADC exhibiting potent in vitro cytotoxicity and in vivo anti-tumor activity while being well-tolerated in a GLP NHP toxicity study. In summary, these data support development of JNJ-95437446 in a first-in-human clinical study (NCT07107230). Citation Format: Benjamin Henley, Linxiao Chen, Megan Siani, Swetha Rao, Yi Fan, Kristen Wiley, Steve Pomerantz, Shalom Goldberg, Onyi Irrechukwu, Simone Buraschi, Suresh Kumar Swaminathan, Krista Burke, Tammy Bush, Bethany Mattson, Heather Deutsch, Gerald Chu, Jacalyn Clawson, Wan Cheung Cheung, Joshua M. Bauml, Ulrike Philippar, Smruthi Vijayaraghavan. JNJ-95437446: Discovery and preclinical characterization of an amivantamab-based EGFR/MET-ADC for solid tumor indications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB473.