CDER-Approved NDA for LUMAKRAS™ (sotarasib)
On May 28, 2021, FDA granted Accelerated Approval to Amgen’s LUMAKRAS™ (sotarasib) for the “treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC).” Of note: Amgen received Priority Review, Breakthrough Therapy, Fast Track, and Orphan Drug designations.
Key findings from FDA’s Multi-Discipline Review: The applicant provided substantial evidence of effectiveness through CodeBreaK 100 (NCT03600883; n=427), a phase 1/2, open-label, single-arm trial. The applicant also provided three real-world, retrospective natural history studies.
Intent of the RWE studies
The applicant conducted three real-world, retrospective natural history studies (Studies 20180277, 20200097, and 20200132) to provide context on outcome measurements in patients receiving standard of care therapies. The studies also provided demographic and clinical characteristics for the intended patient population.
Protocols for RWE generation
The applicant created the three natural history studies using the Flatiron Health-Foundation Medicine Clinico-Genomic Database and the AACR Project GENIE databases. The studies included patients with KRAS G12C-mutated advanced NSCLC receiving a second or later line of therapy. The studies captured real-world progression-free survival for second- (4.0 months), third- (3.1 months), and fourth-line (2.6 months) treatments. They also captured the overall survival for second- (9.5 months), third- (6.7 months), and fourth-line (5.9 months) treatments.
Outcome of the RWE submissions
FDA concluded that the RWE showed that outcomes in the KRAS G12c-mutated advanced NSCLC population were comparable to the overall NSCLC patient population. The agency also noted that these two patient populations share similar demographic and clinical characteristics, albeit with a few differences. The KRAS G12c-mutated advanced NSCLC patient population has a higher proportion of women, current or former smokers, and patients with non-squamous cell carcinoma histology.
FDA also used a retrospective database study (Amanam 2020) to show that immunotherapy is an effective treatment for patients with KRAS-mutated NSCLC. This RWE study helped inform an FDA sub-group analysis of patients who were prescribed a platinum-based chemotherapy and an anti-PDL1 therapy.