Confirmatory trial
Although CodeBreak100 is not a randomized trial, the median OS of 12.5 months compares favorably to median OS times in the range of 7.9-10.3 months reported in randomized phase 3 clinical trials and subgroup analysis of randomized phase 3 trials of docetaxel for patients with KRAS-mutant lung adenocarcinoma, Dr. Skoulidis said in a question-and-answer session.
A confirmatory phase 3 CodeBreaK200 trial of sotorasib versus docetaxel in patients with previously treated KRAS p.G12C-mutated NSCLC is underway. That trial is evaluating PFS as a primary endpoint and OS as a secondary endpoint.
“If the same magnitude of benefit, 12.5 months median overall survival, is confirmed in the larger phase 3 clinical trial, as a clinician I would consider that beneficial for patients, compared to the standard of care,” Dr. Skoulidis said during the session.
Mature data
The updated analysis of the phase 2 CodeBreaK100 study is notable for its mature OS data, updated safety and the first molecular subgroup analyses, according to discussant Christine Marie Lovly, MD, PhD, of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.
“The objective response rate was 37.1%,” she added. “This is a little bit lower than we’re used to for targeted therapies, but remember, this is a different mutation and a very different class of drugs.”
The KRAS G12C inhibitors, several of which are under clinical development, are not tyrosine kinase inhibitors (TKIs), but rather allele-specific inhibitors that target mutant KRAS, trapping it in an inactive conformation, she explained.
Dr. Lovly referenced the exploratory analyses demonstrating efficacy in molecularly defined subgroups, calling it “interesting” that there was no difference in objective response rate between TP53 wild type and mutant tumors.
“We do have data that mutant TP53 seems to confer inferior outcomes for EGFR TKI-directed therapy in patients with EGFR-mutant lung cancer,” she said.
CodeBreaK100 was supported by Amgen, Inc. and partly by a National Institutes of Health Cancer Center Support Grant at Memorial Sloan Kettering Cancer Center.
Dr. Skoulidis reported honoraria from Bristol-Myers Squibb; research funding from AIMM Therapeutics and Amgen; and travel, accommodations, or expenses from Tango Therapeutics. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.