Clinical Data From Full Phase 1 Cohort Of Investigational Sotorasib Published In New England Journal Of Medicine
"CodeBreaK 100 is the largest Phase 1/2, and first-in-human, clinical study for a KRASG12C inhibitor," said
Sotorasib demonstrated confirmed objective response rate (ORR) and disease control rates (DCR) of 35.3% and 91.2%, respectively, in 34 heavily pretreated patients (median of two prior lines of therapy) with NSCLC, who were treated with the 960 mg daily dose (data cutoff of
Anticancer activity was seen across all dose levels in patients with NSCLC, with a confirmed ORR of 32.2% and DCR of 88.1%, and median duration of response of 10.9 months, with 10 of 19 responders still in response as of the data cutoff. Tumor shrinkage was observed in 71.2% of patients at the first week-6 assessment. Median progression-free survival (mPFS) in patients treated with sotorasib was 6.3 months.
Safety and tolerability in patients with NSCLC were consistent with previously seen CodeBreaK 100 results. No dose-limiting toxicities were observed and there were no fatal treatment-related adverse events (TRAEs). The most common TRAEs were diarrhea (25.4%), alanine aminotransferase (ALT) increase (20.3%), aspartate aminotransferase (AST) increase (20.3%), fatigue (10.2%) and nausea (10.2%). Eleven (18.6%) patients had grade 3 or higher TRAEs, one of whom had grade 3 TRAEs of ALT and AST increases that led to discontinuation of treatment.
"These latest results show that sotorasib continues to demonstrate encouraging clinical benefit in heavily pretreated patients with KRAS G12C-mutant tumors," said lead author
The ESMO oral presentation included Phase 1 NSCLC results published in NEJM, as well as data on potential biomarkers of response to sotorasib that demonstrated clinical activity across a range of KRAS G12C mutant allele frequencies (MAFs), PD-L1 tissues expression levels, tumor mutational burden (TMB) plasma levels and tissue co-mutational profiles.
"KRAS G12C is a driver of multiple solid tumor types and is particularly prevalent in non-small cell lung cancer," said
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The RAS gene family, which has been the subject of almost four decades of research, contains some of the most frequently mutated oncogenes in human cancers.1,2 Targeting the KRAS protein, the most commonly altered family member in solid tumors, has been one of the toughest challenges in cancer research.1 A specific mutation known as KRAS G12C, is a major driver of tumor growth, occurring broadly across solid tumor indications. In the
The CodeBreaK clinical trial program for
CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors. Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 1 study is safety, and key secondary endpoints include objective response rate (assessed every six weeks), duration of response and progression-free survival. Patients were enrolled in four dose cohorts: 180 mg, 360 mg, 720 mg and 960 mg, taken orally once a day.
Additional information about CodeBreaK clinical trials can be found at http://www.codebreaktrials.com.
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