Abstract LB025: CKD-703, a novel antibody-drug conjugate targeting cMET with an enhanced therapeutic index in solid tumors

Abstract

Abstract In our pursuit of advancing cancer therapeutics, we introduce CKD-703, a groundbreaking cMET-targeting antibody drug conjugate (ADC) designed to strategically address the challenges posed by cMET overexpression and alteration in various solid tumors. Recognizing the pivotal role of tolerability and efficacy in shaping the therapeutic landscape of ADC, CKD-703 represents a significant advancement, aiming to widen the therapeutic index of cMET-targeted therapies. As we develop CKD-703, an innovative cMET-targeting ADC, we acknowledge the oncogenic potential of cMET alterations, particularly in non-small cell lung cancer (NSCLC), and the prevalent elevation of cMET across various cancers. Antibody drug conjugates targeting cMET (cMET-ADCs) have shown its therapeutic potential in treating cMET positive tumors, irrespective of their dependency on cMET signaling. Clinical success, however, has often been limited to NSCLC patients with the highest cMET levels. In light of this, CKD-703 is crafted to not only improve tolerability but also enhance efficacy, thereby broadening its application to a diverse patient population, including those with moderate cMET expression. To develop a novel cMET-ADC, Chong Kun Dang leverages Synaffix's ADC platform technology, incorporating glycan remodeling to achieve site-specific conjugation of the linker-payload to the antibody and ensuring a homogeneous drug-antibody ratio. These unique characteristics enhance CKD-703's stability in the bloodstream, minimizing the concentration of liberated free payload and significantly improving tolerability. The uniform DAR of CKD-703 contributes to improved pharmacokinetics, ensuring a consistent and sustained therapeutic effect. In comparison to benchmark antibodies, CKD-703 exhibits superior binding affinity to cMET and efficient internalization, resulting in enhanced therapeutic efficacy. This is evidenced in preclinical experiments which performed in several animal models that can mimic the complexities of cMET positive tumors with varying expression levels. The GLP toxicity studies of CKD-703 are ongoing. In conclusion, CKD-703 is a novel cMET-targeting ADC designed to overcome the limitations observed in existing cMET-ADCs in clinical trials as well as significantly improve tolerability and efficacy. By strategically addressing challenges associated with moderate cMET expression levels, CKD-703 emerges as a promising therapeutic candidate, aiming to broaden the therapeutic index in cMET-overexpressing solid tumors. This study highlights the importance of tailored approaches to diverse patient populations in advancing the development of CKD-703 in the pursuit of precision cancer therapies. Citation Format: Kwanwoo Lee, Sue-Youn Kim, Hye-Jin Hong, Eunjeong Park, Jungok Park, Seong-Ho Hong, Daekwon Bae, Nina Ha, Sohn-Ji Yeon, Inchang Hwang, Semi Kim, Yoonseok Lee, Ju-Hee Lee. CKD-703, a novel antibody-drug conjugate targeting cMET with an enhanced therapeutic index in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB025.