Abstract 998P
Background
CKD-702 binds simultaneously to cMET and EGFR and inhibits cancer cell proliferation. Here we report the safety, pharmacokinetic (PK), pharmacodynamic (PD) and preliminary efficacy of CKD-702 from the dose escalation part of a phase I study in patients (pts) with advanced/metastatic NSCLC.
Methods
Pts received intravenous (IV) CKD-702 once every 2 weeks (q2w) using a 3+3 design in 4 escalating doses from 10 mg/kg to 25 mg/kg until progression or unacceptable toxicity. After evaluating dose-limiting toxicity (DLT) at all planned dose levels, additional pts were enrolled at the 3rd and 4th dose levels for safety and PK analysis. Molecular changes were analyzed during the screening period using ctDNA and/or tumor tissue.
Results
At data cut-off (3 Feb 2022), 24 pts were enrolled and received CKD-702. No DLT was reported at any dose level; ≥1 treatment-emergent AEs (TEAEs) occurred in all 24 pts. Common (≥20%) all-grade (Gr) AEs were rash, paronychia, stomatitis, nausea, and hypoalbuminemia. Infusion related reactions (21%) were all Gr 1-2. AEs ≥Gr 3 occurred in 41.67% of pts; 3 pts reported Gr 3 rash (2 maculopapular, 1 acneiform). CKD-702 exposure and half-life increased in a dose-related manner; accumulation (∼1.3×) was confirmed upon repeat-dosing. EGFR-extracellular domain (ECD) tended to increase ∼2-fold regardless of CKD-702 dose; cMET-ECD increased dose-dependently to 20 mg/kg with estimated saturation >20 mg/kg. Among 24 response-evaluable pts, 5 achieved a best time point response of partial response (PR) including 2 confirmed PR: 3 MET ex14 skipping, 1 MET IHC 3+ with EGFR exon 19 deletion, and 1 EGFR L858R with no identified MET-alteration. Among 6 pts with Met ex14 skipping (4 cMET TKI-naïve and 2 cMET TKI-resistant), 3 (all of cMET TKI-naïve) had a best time point response of PR including 2 confirmed. The recommended phase II dose was determined to be 20 mg/kg based on safety, PK, and PD review.
Conclusions
CKD-702 has a manageable safety profile related to EGFR and cMet inhibition, and showed preliminary response in patients with MET ex14 skipping. Part 2 (dose expansion) will use IV CKD-702 20 mg/kg q2w; the planned cohort includes MET-alteration NSCLC.
Clinical trial identification
NCT04667975.
Editorial acknowledgement
Legal entity responsible for the study
Chong Kun Dang Pharmaceutical Corp.
Funding
Chong Kun Dang Pharmaceutical Corp.
Disclosure
D. Kim: Financial Interests, Institutional, Invited Speaker: Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology, Taiwan Lung Cancer Society, Asian Thoracic Oncology Research Group; Financial Interests, Institutional, Writing Engagements: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Chong Keun Dang, Daiichi Sankyo, GSK, Pfizer, MSD, Meck, Novartis, Roche, Takeda, Yuhan; Non-Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, BMS/ONO Pharmaceuticals, Daiichi Sankyo, GSK, Janssen, Meck, MSD, Pfizer, SK Biopharm, Takeda; Non-Financial Interests, Institutional, Member of the Board of Directors: Asian Thoracic Oncology Research Group, Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology; Financial Interests, Institutional, Research Grant: Alpha Biopharma, Amgen, AstraZeneca/MedImmune, Boehringer Ingelheim, BMS, Bridge BioTherapeutics, Chong Keun Dang, Daiichi Sankyo, GSK, Hanmi, Janssen, Merck, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, ; Non-Financial Interests, Institutional, Principal Investigator: Chong Keun Dang; Financial Interests, Institutional, Advisory Role: Scientific advisor for Health insurance review and assessment service, Korea; Financial Interests, Institutional, Other, Travel support: Amgen, Daiichi Sankyo, International Association for the Study of Lung Cancer, Asian Thoracic Oncology Research Group, Taiwan Lung Cancer Society. S. Lee: Financial Interests, Institutional, Other, Honoraria: AstraZeneca/MedImmune, Roche, Merck; Financial Interests, Institutional, Advisory Board: AstraZeneca, Roche, Merck, Pfizer; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Other, Travel, Accommodations, Expenses: Novartis. K. Park: Financial Interests, Personal and Institutional, Invited Speaker, Employee: Chong Kun Dang Pharmaceutical company. D.H. Lee: Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim, Bristol-Myers Squibb, CJ Healthcare, Eli Lilly, ChongKeunDang, Janssen, Merck, MSD, Mundipharma, Novartis, Ono, Pfizer, Roche, Samyang Biopharm, ST Cube, AbbVie, Takeda, Genexine, Menarini, Blueprint Medicine, BC Pharma. All other authors have declared no conflicts of interest.