106P Efficacy and safety of IBI351 (GFH925) monotherapy in metastatic colorectal cancer harboring KRASG12C mutation: Updated results from a pooled analysis of two phase I studies

IBI351 (GFH925) is an irreversibly covalent inhibitor of KRASG12C. Previously, a pooled analysis of two phase I studies reported preliminary efficacy and safety of IBI351 (GFH925) monotherapy in metastatic colorectal cancer (CRC) harboring KRASG12C mutation (Ying Yuan, et al., ASCO 2023). Herein, we present updated results of these two studies with extended follow-up. The studies enrolled eligible metastatic CRC patients (pts) with KRASG12C. Pts received IBI351 (GFH925) orally at dose levels of 700mg once daily (QD) or 450/600/750mg twice daily (BID). The primary endpoint was objective response rate (ORR) assessed by investigator per RECIST v1.1. As of June 13, 2023, a total of 56 pts were enrolled (median age: 58.0 years; male: 60.7%; ECOG PS 1: 73.2%; ≥2 prior lines of treatment: 60.7%; liver metastasis: 60.7%). The median treatment duration was 172.5 days (range: 8-481) and 26 pts (46.4%) were still on treatment. For 48 pts at 600mg BID, confirmed ORR was 45.8% (95%CI: 31.4%-60.8%) and disease control rate (DCR) was 89.6% (95%CI: 77.3%-96.5%). Median duration of response (DOR) was not reached with events occurring in 5 (22.7%) pts. DOR rates were 65.5% (95%CI: 34.4%-84.5%) at 6 months and not reached at 9 months. In pts of all dose levels, treatment-related adverse events (TRAEs) occurred in 53 (94.6%) pts while majority of them were grade 1-2. Grade 3 TRAEs occurred in 13 (23.2%) pts. Neither grade 4-5 TRAEs nor treatment-related serious adverse events (TRSAEs) occurred. The most common TRAEs included anemia (48.2%), white blood cell count decreased (30.4%), blood bilirubin increased (26.8%) and pruritus (26.8%). TRAEs leading to dose reduction and interruption occurred in 6 (10.7%) and 12 (21.4%) pts. No TRAEs leading to treatment discontinuation or death occurred. The updated results of IBI351 (GFH925) monotherapy showed promising durable efficacy and manageable safety in metastatic CRC harboring KRASG12C mutation. During longer follow-up, these two ongoing studies are expected to provide more robust evidence.