The FDA has granted accelerated approval to sotorasib for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer, as determined by an FDA-approved test, who have received at least one prior systemic therapy.
The FDA has granted accelerated approval to sotorasib (Lumakras) for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy, according to a press release from Amgen.1
Based on the objective response rate (ORR) and duration of response (DOR) achieved with the agent in this patient population, the FDA saw fit to approve sotorasib more than 2 months ahead of the Prescription Drug User Fee Act target action date of August 16, 2021. The data that provided supporting evidence for the FDA approval came from the phase 2 CodeBreak 100 trial (NCT03600883).
"Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C-mutated non-small cell lung cancer," said Bob T. Li, MD, PhD, MPH, principal investigator at Memorial Sloan Kettering Cancer Center, in the press release. "Patients with non-small cell lung cancer who have progressed beyond first-line treatment face a poor prognosis and have limited treatment options available to them. Sotorasib delivers a new option for these patients, and it is the first KRAS-targeted therapy to be approved after nearly four decades of research."
The first-in-human, open-label, multicenter study enrolled patients with solid tumors with KRAS G12C mutations who had received at least 1 prior line of systemic anticancer therapy. The NSCLC cohort included 124 patients. All patients in the cohort were treated with 960 mg oral sotorasib once daily. Eighty-one percent of patients had progressed on both platinum-based chemotherapy and PD-1/L1 inhibitors before joining the trial.
A confirmed ORR of 36% (95% CI: 28-45), and the disease control rate was 81% (95% CI: 73-87). According to previously reported at the World Conference on Lung Cancer, among all responders, the median best reduction in tumor size was 60%.2 The median time to objective response was 1.4 months and the median DOR was 10 months.1,2
Further, at a median follow-up of 12.2 months, the median progression-free survival was 6.8 months.
Treatment-related adverse events (TRAEs) observed with sotorasib were predominantly grade 1 or 2 in severity and no treatment-related deaths were reported in the study. Grade 3 TRAEs occurred in 25 (19.8%) patients and 1 patient (0.8%) reported a grade 4 TRAE. The most frequently reported TRAEs of any grade were diarrhea (31.0%), nausea (19.0%), increased alanine aminotransferase (15.1%), and increased aspartate aminotransferase (15.1%). Treatment discontinuation rates due to TRAEs occurred in 7.1% of patients.2
"The FDA approval of Lumakras is a breakthrough moment for patients with KRAS G12C-mutated non–small cell lung cancer because there is now a targeted therapy for this common, but previously elusive, mutation," said David M. Reese, MD, executive vice president of Research and Development at Amgen, in a statement. "KRAS has challenged cancer researchers for more than 40 years with many deeming it as 'undruggable. The Lumakras development program was a race against cancer for Amgen's scientists and clinical trial investigators who together have now successfully delivered this new medicine to patients in less than three years—from first patient dosed to [United States] regulatory approval."
1. FDA approves LUMAKRAS™ (sotorasib), the first and only targeted treatment for patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer. News release. May 28, 2021. Accessed May 28, 2021. https://bit.ly/3wGiklr
2. Li BT, Skoulidis F, Falchook G, et al. CodeBreaK 100: Registrational Phase 2 Trial of Sotorasib in KRAS p.G12C Mutated Non-small Cell Lung Cancer. Presented at: International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer; January 28-31, 2021; virtual. Abstract PS01.07.