The KRASG12C inhibitor divarasib can produce responses in patients with solid tumors, according to research published in The New England Journal of Medicine.
Divarasib demonstrated antitumor activity in several cancers, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).
These results come from a phase 1 trial (ClinicalTrials.gov identifier: NCT04449874) of 137 patients with KRASG12C-mutated advanced solid tumors.
Most patients had NSCLC (n=60) or CRC (n=55), but they also had other solid tumors (n=22), the most common of which were pancreatic cancer (n=7) and cholangiocarcinoma (n=7). The patients’ median age was 65 (range, 30-85) years, and all but 1 patient had received prior systemic therapies.
The patients were treated with 50 mg to 400 mg of divarasib, given once daily in 21-day cycles. The 400 mg dose was identified as the expansion dose.
Among patients with NSCLC, the objective response rate (ORR) was 53.4%. One patient had a complete response, and 34 had a partial response. The median time to response was 1.3 months, and the median duration of response was 14.0 months. The median progression-free survival (PFS) was 13.1 months.
For NSCLC patients who received the 400 mg dose, the ORR was 56.4%. The median duration of response in this group was 11.9 months, and the median PFS was 13.7 months.
Among patients with CRC, the ORR was 29.1%. One patient had a complete response, and 19 had a partial response. The median time to response was 2.2 months, and the median duration of response was 7.1 months. The median PFS was 5.6 months.
CRC patients who received the 400 mg dose had an ORR of 35.9%. The median duration of response in this group was 7.7 months, and the median PFS was 6.9 months.
In the patients with other solid tumors, all of whom were treated with 400 mg of divarasib, the ORR was 36%. All 8 responses were partial responses.
There were no dose-limiting toxicities in the entire cohort. Nearly all patients (93%) had at least 1 treatment-related adverse event (TRAE). The most common TRAEs were nausea (74%), diarrhea (61%), and vomiting (58%).
Grade 3-4 TRAEs occurred in 18% of patients with NSCLC and in 7% of those with CRC. The most common grade 3-4 TRAEs were aspartate aminotransferase level increase in the NSCLC group (7%) and diarrhea in the CRC group (5.5%).
Overall, TRAEs resulted in dose modifications in 30% of patients, dose interruptions in 20%, dose reductions in 14%, and discontinuations in 3%.
“The safety profile and encouraging single-agent antitumor activity of divarasib make it a promising clinical candidate both as a single agent and in combination with other anticancer therapies,” the researchers concluded.
Studies of divarasib in combination with other agents are ongoing.
Disclosures: This research was supported by Genentech. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
This article originally appeared on Cancer Therapy Advisor
Sacher A, LoRusso P, Patel MR, et al. Single-agent divarasib (GDC-6036) in solid tumors with a KRAS G12C mutation. N Engl J Med. Published online August 24, 2023. doi:10.1056/NEJMoa2303810