FDA Grants Sotorasib a Priority Review for KRAS G12C+ Advanced NSCLC

The FDA accepted a new drug application (NDA) for sotorasib and granted it a priority review for the treatment of patients with KRAS G12C–mutant locally advanced or metastatic non–small cell lung cancer (NSCLC) following at least 1 prior systemic treatment.1

A Prescription Drug User Fee Action (PDUFA) date of August 16, 2021, was set as a target action date for a decision on the potential sotorasib approval. The NDA was also accepted into the FDA’s Real-Time Oncology Review Pilot Program.

Sotorasib is the first KRAS G12C inhibitor to enter the clinic. As KRAS G12C is one of the most common driver mutations in NSCLC, there is a high unmet need for this patient population.

Data from the phase 2 CodeBreak 100 trial (NCT03600883) supported the NDA. 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 trial included 126 patients. All patients 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 prior to joining the trial.

A confirmed objective response rate of 37.1% was seen with 3 patients achieving a complete response and 43 with partial responses. The disease control rate was 80.6%. Among all responders, the median best reduction in tumor size was 60%. The median time to objective response was 1.4 months and the median duration of response was 10 months.2

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 mostly grade 1 or 2 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 all-grade TRAEs (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.

The developer, Amgen, also submitted Marketing Authorization Applications in the European Union, Australia, Brazil, Canada, and the United Kingdom.

A breakthrough therapy designation was also granted to sotorasib in both the United States and China.

_References

_{FDA Grants Sotorasib Priority Review Designation For The Treatment Of Patients With KRAS G12C-Mutated Locally Advanced Or Metastatic Non-Small Cell Lung Cancer. News release. February 16, 2021. Accessed February 16, 2021. https://bit.ly/3diXBxN}

_{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.}