On January 29, 2021 Amgen (NASDAQ: AMGN) reported that its investigational KRASG12C inhibitor sotorasib was granted Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) (Press release, Amgen, JAN 29, 2021, View Source [SID1234574989]). The designation is for the treatment of patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior systemic therapy. This is the first BTD submission for Amgen in China, as well as the first under Amgen’s strategic collaboration with BeiGene.
NSCLC is the most common form of lung cancer, accounting for approximately 80-85% of all cases worldwide.1 KRAS G12C is the most common KRAS mutation in NSCLC.2,3 The mutation is a biomarker of poor prognosis in Chinese NSCLC patients, which may be improved by G12C-specific inhibitors.4 Research has shown that about 3-5% have the KRAS G12C mutation – found most commonly in smokers.4,5
"Given that Breakthrough Therapy Designation is a new pathway in China, we are pleased to receive this designation for sotorasib," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "This designation underscores the importance of sotorasib and we look forward to working with regulatory authorities in China to bring the first potential targeted therapy to NSCLC patients with the KRAS G12C mutation."
The Breakthrough Therapy Designation is supported by the positive CodeBreaK 100 Phase 2 results in patients with advanced NSCLC whose cancer had progressed despite prior treatment with chemotherapy and/or immunotherapy. In the study, treatment with sotorasib demonstrated durable anticancer activity with a positive benefit-risk profile.6 These results will be presented at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer (WCLC) Presidential Symposium from 3:50-4 p.m. PST on Friday, Jan. 29.
The NMPA’s BTD process is designed to expedite the development and review of therapies that are intended for the prevention or treatment of serious life-threatening diseases for which there is no existing treatment and where preliminary evidence indicates advantages of the therapy over available treatment options.7 This designation shows the potential for sotorasib to become the first targeted treatment available in China for KRAS G12C-mutated NSCLC.
Amgen has taken on one of the toughest challenges of the last 40 years in cancer research by developing sotorasib, the first KRASG12C inhibitor to enter the clinic.8 Sotorasib is being studied in the broadest clinical program exploring 10 combinations with global sites spanning across four continents. In just over two years, the sotorasib clinical trial program has also established the deepest clinical data set with nearly 700 patients studied across 13 tumor types.
The CodeBreaK clinical development program for Amgen’s investigational drug sotorasib is designed to treat patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers. As the most advanced KRAS G12C clinical development program, CodeBreaK has enrolled nearly 700 patients across 13 tumor types since its inception.
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. The Phase 2 trial in colorectal cancer is fully enrolled and topline results are expected in 2021.
A global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in patients with KRAS G12C-mutated NSCLC (CodeBreaK 200) is currently recruiting. Amgen also has more than 10 Phase 1b combination studies across various advanced solid tumors (CodeBreaK 101) open for enrollment.