CodeBreaK 100 update confirms sotorasib efficacy in KRAS-mutated NSCLC
medwireNews: The KRAS inhibitor sotorasib achieves clinical benefit in individuals who have received prior treatment for advanced non-small-cell lung cancer (NSCLC) harboring a KRAS G12C mutation, suggest data from the phase 2 cohort of CodeBreaK 100.
Noting that these findings validate those from the phase 1 portion of the trial, the presenting author told delegates of the IASLC 2020 World Conference on Lung Cancer that “[a]fter four decades of scientific effort, sotorasib may have the potential to be the first targeted treatment option for this patient population with a high unmet need.”
The current cohort included 126 patients with locally advanced or metastatic NSCLC and a KRAS G12C mutation who had received up to three prior lines of therapy. Participants received oral sotorasib (previously called AMG 510) – a first-in-class, highly selective KRAS G12C inhibitor – at a dose of 960 mg/day until disease progression.
Over a median follow-up of 12.2 months, the primary endpoint of objective response rate (ORR) was achieved by 37.1% of patients, with complete responses in 2.4% and partial responses in 34.7%. A further 43.5% of participants had stable disease, which gave a disease control rate of 80.6%.
Responses occurred at a median of 1.4 months and lasted for a median of 10.0 months, reported Bob Li (Memorial Sloan Kettering Cancer Center, New York, USA), adding that 43% of the 46 responders remained on treatment and progression-free at data cutoff.
He also presented exploratory analyses showing that responses to sotorasib occurred “across the range of PD-L1 expression levels and STK11/KEAP1 co-occurring mutations.” For instance, the ORR was 48% for patients with a PD-L1 tumor proportion score of less than 1%, 39% for those with a score of 1–49%, and 22% for those with score of 50% or higher.
The median progression-free survival in the overall cohort was 6.8 months.
With regard to safety, treatment-related adverse events (TRAEs) of grade 3 occurred in 19.8% of patients, with elevations in alanine aminotransferase and aspartate aminotransferase the most frequent events, at 6.3% and 5.6%, respectively. One patient experienced grade 4 pneumonitis and dyspnea.
TRAEs resulted in dose modifications in 22.2% of participants and discontinuations in 7.1%, but there were no deaths attributable to TRAEs.
Li noted that sotorasib has been granted breakthrough therapy designation by the US FDA and that the “[c]onfirmatory phase 3 CodeBreaK 200 trial is currently enrolling.”
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