Results from the phase 2 cohort of the CodeBreaK 100 clinical study evaluating investigational Sotorasib ( AMG 510 ) in 126 patients with KRAS G12C-mutated advanced non-small cell lung cancer ( NSCLC ) were presented during IASLC 2020 WCLC.
Sotorasib has demonstrated a confirmed objective response rate ( ORR ) and disease control rate ( DCR ) of 37.1% and 80.6%, respectively, and a median duration of response of 10 months ( data cutoff of Dec.1, 2020; median follow-up time was 12.2 months ).
The results have also highlighted that Sotorasib is the first KRASG12C inhibitor to show progression-free survival ( median of 6.8 months ) in a phase 2 study, which is consistent with earlier phase 1 results in previously treated patients with KRAS G12C-mutated advanced NSCLC.
Patients were treated with Sotorasib 960 mg once daily orally. Prior to the trial, 81% of patients had progressed on both Platinum-based chemotherapy and PD1/L1 inhibitors, with the remainder progressing after having received one of these therapies.
Over 80% of patients achieved disease control, including three complete responses and 43 partial responses, and the median best tumor shrinkage among all responders ( n=46 ) was 60%.
The median time to objective response was 1.4 months.
Sotorasib had a favorable benefit-risk profile with most treatment-related adverse events ( TRAEs ) mild-to-moderate ( grade 1 or 2 ) and no treatment-related deaths.
Grade 3 TRAEs were reported in 25 ( 19.8% ) patients and only 1 patient ( 0.8% ) reported a grade 4 TRAE.
The most frequently reported TRAEs ( any grade ) were diarrhea ( 31.0% ), nausea (19.0%), increased alanine aminotransferase ( 15.1% ) and increased aspartate aminotransferase ( 15.1% ). TRAEs led to treatment discontinuation in only 7.1% of patients.
In exploratory analyses, encouraging tumor response to Sotorasib was observed across a range of biomarker subgroups, including patients with negative or low PD-L1 expression level and those with STK11 mutation. This co-mutation has been associated with poor outcomes in NSCLC patients treated with checkpoint inhibitors and chemotherapy.
The CodeBreaK clinical development program for Sotorasib is designed to treat patients with an advanced solid tumor with the KRAS G12C mutation.
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 2 study was centrally assessed objective response rate.
The phase 2 trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST at baseline.
NSCLC accounts for 80-85% of all lung cancers, and most patients ( 66% ) have advanced or metastatic disease at initial diagnosis.
KRAS G12C is one of the most common driver mutations in NSCLC and there is a high unmet need and poor outcomes associated in the second-line treatment of KRAS G12C driven NSCLC.
In the U.S., about 13% of patients with NSCLC harbor the KRAS G12C mutation, and each year approximately 25,000 new patients in the U.S. are diagnosed with KRAS G12C-mutated NSCLC. ( Xagena )
Source: Amgen, 2021