The majority of treatment-related adverse events (TRAEs) were grade 1-2 in severity, and no patients experienced dose-limiting toxicities during the 28 days following initial treatment.
The combination of sotorasib (Lumakras, Amgen) plus panitumumab (Vectibix, Amgen) showed promising efficacy and safety in patients with KRAS G12C-mutated advanced colorectal cancer (CRC). These data were from the first combination results of the phase 1b/2 CodeBreaK 101 trial in this patient population, which were presented at the European Society of Medical Oncology 2021 Virtual Congress.
The objective response rate was 27% among 26 patients with refractory CRC, whereas the disease control rate was 81%. In an expansion cohort of sotorasib-naïve patients with refractory CRC, 33% showed a response.
"We are excited by these CodeBreaK 101 data, which show encouraging response rates that were much higher than the 9.7% response rate observed with LUMAKRAS monotherapy and highlight the importance of combination therapy for patients with KRAS G12C-mutated advanced colorectal cancer," said David M. Reese, MD, executive vice president of Research and Development at Amgen, in a press release. "Based on these results and the urgent need for new therapies, we are pleased to announce the initiation of a new phase 3 trial with LUMAKRAS plus Vectibix in the third-line setting. This new trial, along with our doublet and triplet combination trials in colorectal cancer, demonstrates our commitment to delivering a new treatment option for metastatic CRC patients who harbor the KRAS G12C mutation."
Thirty-one patients with heavily pretreated KRAS G12C-mutated metastatic CRC were placed in the dose exploration and dose expansion cohorts for the combination of sotorasib and panitumumab. The majority of treatment-related adverse events (TRAEs) were grade 1-2 in severity, and no patients experienced dose-limiting toxicities during the 28 days following initial treatment. The most common TRAEs included dermatitis acneiform, dry skin, nausea, diarrhea, hypokalemia, hypomagnesemia, pruritus, and rash.
"With treatment response rates being as low as 2% in patients with colorectal cancer who progress in advanced stages, developing new treatment approaches for these patients is of critical interest," said primary study investigator Marwan G. Fakih, MD, in a press release. "Preclinical research has indicated that the addition of an EGFR inhibitor to KRASG12C inhibition can be synergistic, and now we have the first clinical data indicating the combination of sotorasib and panitumumab has the potential to be a safe and effective treatment for patients with KRAS G12C-mutated advanced CRC."
LUMAKRAS™ (Sotorasib) Combined With Vectibix® (Panitumumab) Showed Encouraging Efficacy And Safety In Patients With KRAS G12C-Mutated Colorectal Cancer. Amgen. September 16, 2021. Accessed September 17, 2021. https://www.amgen.com/newsroom/press-releases/2021/09/lumakras-sotorasib-combined-with-vectibix-panitumumab-showed-encouraging-efficacy-and-safety-in-patients-with-kras-g12cmutated-colorectal-cancer