998P A phase I study of CKD-702, an EGFR-cMET bispecific antibody, in advanced or metastatic non-small cell lung cancer (NSCLC)

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. 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. 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. 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.