1622P - D-1553 in patients with KRAS G12C mutated advanced pancreatic cancer (pca)

Background

KRAS mutations are found in approximately 90% of PCa, of which 1-2% are KRAS G12C. D-1553 has shown clinical activity in patients (pts) with KRAS G12C mutated non-small cell lung cancer and colorectal cancer. Here, we report preliminary data of D-1553 in KRAS G12C mutated advanced PCa.

Methods

Pts with KRAS G12C mutated advanced PCa (with no standard treatment available or refractory or intolerant to existing standard treatment) were enrolled and received D-1553 at the recommended phase II dose of 600 mg BID orally. Study endpoints included safety, pharmacokinetics (PK), and efficacy (RECIST, v1.1). Efficacy endpoints included objective response, disease control (defined as an objective response or stable disease) and progression-free survival. Safety was also assessed.

Results

As of 01 March 2023, a total of 10 pts with advanced PCa (median age 67.5 years [range 48–78]; 60% female; 70% Asian; 80%/20% ECOG PS 0/1; 100% stage IV disease at baseline; 40% with ≥ 2 prior lines of therapy [median 1]) were enrolled and treated with D-1553. At data cutoff, 5 (50%) pts remained on treatment. The median duration of treatment and follow-up were 7.15 months (range 1.22-8.94) and 8.10 (range 4.47-9.23) months, respectively. The objective response rate was 50.0% (5/10, including 1 confirmed complete response, 3 confirmed partial response [PR], and 1 unconfirmed PR) and disease control rate was 80.0% (8/10). Median progression-free survival was 8.54 (95% CI 1.25-NA) months. Treatment-related adverse events (TRAEs) of any grade occurred in 7 (70.0%) pts, with the most commonly (≥ 20%) reported as increased ALT, increased AST, decreased appetite, and diarrhoea. Grade 3 TRAEs occurred in 2 (20%) pts, including increased ALT, increased AST and increased alkaline phosphatase. There was no grade > 3 TRAEs, nor TRAEs leading to death or D-1553 permanent discontinuation.

Conclusions

D-1553 is well tolerated and has shown promising anticancer activity in pts with pre-treated KRAS G12C mutated advanced PCa. This study is ongoing, and more results will be presented at the meeting.

Clinical trial identification

NCT04585035, NCT05383898.

Editorial acknowledgement

Legal entity responsible for the study

InventisBio Co., Ltd.

Funding

InventisBio Co., Ltd.

Disclosure

S. Kondo: Financial Interests, Institutional, Speaker’s Bureau: Abbie; Financial Interests, Institutional, Research Grant: Eisai, Astellas, Incyte, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Incyte, Chugai, Eisai. X. Liu, Y. Zhang, X. Xie: Financial Interests, Personal, Full or part-time Employment: InventisBio. Z. Xiang, Z. Shi, Y. Wang, L. Zhang: Financial Interests, Personal, Full or part-time Employment: InventisBio; Financial Interests, Personal, Stocks/Shares: InventisBio. N. Yamamoto: Financial Interests, Personal, Invited Speaker: Ono, Chugai, Daiichi Sankyo, Eisai; Financial Interests, Personal, Advisory Board: Eisai, Takeda, Boehringer Ingelheim, Cimic, Chugai, Healios; Financial Interests, Institutional, Invited Speaker, Principal Investigator in industry sponsored trial: Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Kyowa-Hakko Kirin, Takeda, Ono, Janssen Pharma, MSD, Merck, GSK, Sumitomo Dainippon, Chiome Bioscience, Otsuka; Financial Interests, Institutional, Invited Speaker, Principal investigator in industry sponsored trial: Carna Biosciences, Genmab, Shionogi, Toray; Financial Interests, Institutional, Research Grant, Principal investigator in industry sponsored trial: Rakuten Medical, InventisBio Co., Ltd. All other authors have declared no conflicts of interest.