Patients with pretreated KRAS p.G12C mutated NSCLC showed improvement across all patient subgroups when treated with sotorasib, according to an exploratory analysis of the phase 2 CodeBreak 100 trial and presented at the ASCO annual meeting. 

In the registrational trial, sotorasib demonstrated an objective response rate (ORR) of 37.1% (95% Cl: 28.6, 46.2) and a median progression-free survival (PFS) of 6.8 months (95% Cl: 5.1, 8.2) in patients with pretreated KRAS p.G12C mutated NSCLC.  

Additionally, the researchers of the CodeBreak 100 trial observed tumor response in patients bearing co-mutations in STK11, a driver of poor clinical outcomes with standard of care.  

Ferdinandos Skoulidis, MD, PhD, MRCP, from University of Texas MD Anderson Cancer Center conducted an exploratory analysis to review the efficacy of sotorasib across an extended set of patient subgroups by key baseline characteristics and biomarkers. 

Eligible patients with advanced NSCLC harboring KRAS p. G12C received 960mg sotorasib orally once daily and received prior standard therapies.  

The primary outcome of the study was ORR assessed by central review and key secondary outcomes included PFS, overall survival, and safety.  

Skoulidis and colleagues analyzed KRAS p.G12C mutant allele frequency (MAF) and tumor mutational burden (TMB) by next-generation sequencing (NGS) using tissue samples and determined mutational status of individual genes by NGS using tissue and/or plasma samples.  

They studied the correlations between response and KRAS p.G12C MAF, TMB, or co-mutations in subsets of patients who had available respective results, according to the abstract. 

124 patients were eligible for evaluation and showed an ORR of 37.1% (95% CI, 28.6, 46.2). 

Patients 65 years and older had an ORR of 44.1% while patients younger than 65 years had an ORR of 30.8%. 

Additionally, the researchers found that patients who received a single line or multiple lines of prior therapy had an ORR of 39.6% and 35.2%, respectively.  

They also reported marked improvement among patients with KRAS p.G12C MAF, TMB, as well as other co-mutations. 

“In the exploratory analyses of the phase 2 CodeBreaK 100 trial, the clinical benefit of sotorasib was observed across patient subgroups,” the researchers wrote. “Overall survival and updated exploratory analyses will be presented.” 

Disclosure: Skoulidis reports receiving honoraria from Bristol-Myers Squibb, research funding from AIMM Therapeutics and Amgen and travel funds from Tango Therapeutics. 


By Dave Quaile, /alert Contributor