Phase I Dose-Escalation Study of IBI351 (GFH925) Monotherapy in Patients with Advanced Solid Tumors.

3110 Background: IBI351(GFH925) is an irreversibly covalent inhibitor of KRASG12C. In this first-in-human dose-escalation study, we report the preliminary safety and anti-tumor activity of IBI351 (GFH925) in patients (pts) with advanced solid tumors harboring the KRAS p.G12C mutation. Methods: Pts with locally advanced, recurrent or metastatic solid tumors with KRASG12C mutation for whom standard therapy had failed were enrolled. Phase I dose escalation had an accelerated titration design for dose level 250mg QD and a BOIN design with 450/700/900mg QD. The primary end points were safety and tolerabilityThe secondary end points were pharmacokinetics (PK) and anti-tumor activity of IBI351(GFH925) monotherapy per RECIST v1.1. Results: As of Feb 07 2022, 15 pts (13 men, 2 women; median age: 62 yrs, range: 48–74 yrs) were enrolled, among whom 12 had non-small cell lung cancer (NSCLC), and 3 had colorectal cancer (CRC). 4 pts had ≥3 prior lines of treatment (tx). Median tx duration was 66.5 ds (range: 21–98 ds). No dose-limiting toxicity (DLT) or any ≥grade 3 treatment-related adverse events were observed in any dose cohorts. A total of 12 patients (80.0%) had treatment-related adverse events (grade 1, n = 6; grade 2, n = 6). By investigator-assessment, tumor response was evaluated in 9 pts (4 with ≥2 assessments); 6 pts had not reached their first assessment. 2 pts had PR (1 NSCLC at wks 12, 450mg, tx ongoing; 1 CRC at wks 6, 700mg, tx ongoing), 4 pts (NSCLC) had SD, and 3 pts had PD (1 NSCLC at wks 12, 2 CRC at wks 6). As data cut-off date, 11 pts were continuing to receive IBI351 (GFH925). Conclusions: IBI351(GFH925) was well-tolerated without unanticipated adverse events across all doses explored in pts with advanced solid tumors harboring the KRAS p.G12C mutation. The data also demonstrated the preliminary efficacy signal of IBI351 (GFH925) in previously treated advanced NSCLC and CRC. Clinical trial information: NCT05005234.