Abstract 1622P
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.
Resources from the same session
1626P - A novel endoscopic ultrasound guided extended-release siRNA implant targeting KRASG12D/V in localized pancreatic cancer
Presenter: Anna Varghese
Session: Poster session 22
1629P - Modified-FOLFIRINOX-losartan followed by chemoradiotherapy for locally advanced pancreatic cancer: A phase II study
Presenter: Alshaimaa Alhanafy
Session: Poster session 22
1630P - Phase I/Ib study of SHP2-ERK inhibition in KRASm pancreatic cancer (SHERPA trial) and preclinical identification of potential resistance markers
Presenter: Ashwini Cheryl Kanhailal
Session: Poster session 22
1631P - Phase I study of endoscopic ultrasound (EUS)-guided NBTXR3 delivery activated by radiotherapy (RT) for locally advanced or borderline resectable pancreatic cancer (LAPC or BRPC)
Presenter: Gabriela Fuentes
Session: Poster session 22
1632P - Organoids as tools for functional precision oncology in advanced pancreatic cancer
Presenter: Alice Boileve
Session: Poster session 22
1633P - Development and clinical validation of news transcriptomic tools for predicting the response to individual drug of the mfolfirinox regimen in patients with pancreatic ductal adenocarcinoma
Presenter: Nicolas Fraunhoffer
Session: Poster session 22
1634P - Extensive molecular profiling of KRAS wild-type versus KRAS mutant pancreatic ductal adenocarcinoma on 233 patients
Presenter: Jeanne Lena
Session: Poster session 22