Dr Loong on the Efficacy of D3S-001 in KRAS G12C Inhibitor–Resistant NSCLC

“Overall, [D3S-001] was a well tolerated treatment [with] a very reasonable response rate, especially in patients who had prior KRAS G12C inhibitors.”

Herbert H F Loong, MBBS(HK), PDipMDPath(HK), MRCP(UK), FRCP Edin, FHKCP, FHKAM(Medicine), FASCO, a clinical associate professor in the Department of Clinical Oncology and the deputy medical director of the Phase 1 Clinical Trials Centre at The Chinese University of Hong Kong; as well as an honorary consultant in the Department of Clinical Oncology at the Prince of Wales Hospital/New Territories East Cluster, Hospital Authority, discussed findings from a study investigating the efficacy of monotherapy with the next-generation, GDP-bound KRAS G12C inhibitor D3S-001 in patients with KRAS G12C inhibitor–resistant non–small cell lung cancer (NSCLC).

Among the 20 patients with pretreated NSCLC enrolled in the trial, the overall response rate was 30.0%, and the disease control rate was 80.0%. The duration of response was encouraging as well, at 8.2 months (95% CI, 1.5-not calculable), Loong said.

As this was an early-phase trial, one of the primary objectives was safety, he noted. D3S-001 was well tolerated; the most common adverse effects (AEs) were gastrointestinal AEs, such as nausea and vomiting. Liver dysfunction was another notable toxicity, he stated. These toxicities were primarily low grade; 1 patient experienced grade 3 increased lipase levels, and the remaining patients had grade 1 and 2 AEs. Importantly, no patients developed interstitial lung disease, according to Loong.

Disclosures: Loong reported being a consultant for Boehringer-Ingelheim, Celgene, Eli Lilly, Illumina, Novartis, Merck Serono, Takeda, and George Clinical; being a member of the speaker’s bureau for AbbVie, Bayer, Eisai, Eli Lilly, Guardant Health, and Novartis; receiving institutional grant/research support from MSD, Mundipharma, and Novartis; and attending meetings on behalf of/receiving travel support from Bayer, Boehringer-Ingelheim, MSD, Novartis, and Pfizer.