Abstract 106P
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Clinical trial identification
NCT05005234; NCT05497336.
Editorial acknowledgement
Corresponding author: Kefeng Ding.
Legal entity responsible for the study
Innovent Biologics, Inc., Suzhou, Jiangsu, China.
Funding
Innovent Biologics, Inc., Suzhou, Jiangsu, China.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
362P - Efficacy and safety of MCLA-129, an anti-EGFR/c-MET bispecific antibody, in head and neck squamous cell cancer (HNSCC)
Presenter: Irene Braña
Session: Poster Display
Resources:
Abstract
363P - Effect of financial distress and mental well-being of patients with early vs advanced oral cancer on informal caregiver's quality of life: A prospective real-world data from public health sector hospital
Presenter: Abhinav Thaduri
Session: Poster Display
Resources:
Abstract
364P - Artificial intelligence provides more accurately neck lymph nodes auto-segmentation in radiotherapy
Presenter: chiencheh Chen
Session: Poster Display
Resources:
Abstract
365P - Radiotherapy treatment outcomes and treatment compliance of nasopharyngeal cancer patients in Sabah: A retrospective analysis
Presenter: Anbarasan Anbazagan
Session: Poster Display
Resources:
Abstract
366P - Pre-treatment oral fungal microbiome and nasopharyngeal carcinoma prognosis: A population-based cohort study in southern China
Presenter: Yufeng Chen
Session: Poster Display
Resources:
Abstract
367P - Prevalence and association of sarcopenia with mortality in patients with head and neck cancer: A meta-analysis
Presenter: Claire Lim
Session: Poster Display
Resources:
Abstract
368P - Distinct gene expression profiling explored using nanostring tumor signalling 360 panel with validations in different clinical stages of oral submucous fibrosis patients: A first Indian study
Presenter: Yasasve Madhavan
Session: Poster Display
Resources:
Abstract
370P - Low-dose nivolumab with induction chemotherapy for inoperable HNSCC in 111 patients: Response rates, survival, and implications for LMICs
Presenter: Josh Thomas Georgy
Session: Poster Display
Resources:
Abstract
371P - The role of FDG-PET/CT in the assessment of response to radiation therapy in head and neck cancers: A systematic review and meta-analysis
Presenter: Felix Wijovi
Session: Poster Display
Resources:
Abstract
372P - Effectiveness of HAN-MI-RADS (head and neck molecular imaging-reporting and data system) criterion in head and neck squamous cell carcinoma post concurrent chemoradiotherapy
Presenter: Manoj Gupta
Session: Poster Display
Resources:
Abstract