Amgen’s Lumakras (sotorasib) combined with Vectibix (panitumumab) demonstrated ‘encouraging efficacy and safety’ in patients with KRAS G12C-mutated colorectal cancer (CRC), updated data from the company’s phase 1b CodeBreaK 101 study revealed.
Overall, the combination of Lumakras and Vectibix – the company’s monoclonal anti-epidermal growth factor receptor (anti-EGFR) antibody – achieved a confirmed objective response rate of 30% in patients with chemo-refractory metastatic colorectal cancer (mCRC).
CRC is the second leading cause of cancer deaths worldwide, accounting for 10% of all cancer diagnoses. KRAS mutations are among the most common genetic alterations in colorectal cancers, with the KRAS G12C mutation present in approximately 3-5% of colorectal cancers. These patients face a dismal prognosis and have very limited treatment options, Amgen reported.
David Reese, executive vice president of Research and Development at Amgen, said: “Treatment response rates can be as low as 2% in this patient population, and the current standard of care offers a median progression-free survival benefit of two months, so developing new treatment options is critically important for patients.”
In total, 40 patients with heavily pre-treated KRAS G12C-mutated chemo-refractory mCRC were enrolled in the dose expansion cohort for the combination treatment.
Disease control was seen in 37 patients for a total of 92.5% with a median progression free survival of 5.7 months. There were no apparent differences found in the efficacy between left-sided and right-sided tumours.
Tumour shrinkage of any magnitude was observed in 88% of patients, and the median duration of treatment was 5.9 months, with 25% of patients remaining on treatment at the time of data cut-off.
With a median follow up of 8.8 months, the company outlined that median overall survival was not yet reached. Moreover, treatment-related adverse events reported with the combination were consistent with known safety profiles of the individual medicines.
Reese added: “This data is encouraging as we continue to focus on combination approaches in colorectal cancer, including advancing CodeBreaK 300, the phase 3 Lumakras plus Vectibix trial in the chemotherapy-refractory patient population.”
Yasutoshi Kuboki, chief, department of experimental therapeutics, National Cancer Center Hospital East, Japan, also commented on the positive results: “There is a significant treatment gap for patients with KRAS G12C-mutated colorectal cancer and it is imperative that we continue to explore and develop precision therapies, like [Lumakras], for these patients.”