Sotorasib Plus Panitumumab Approved by FDA for KRAS G12C-Mutated mCRC

The FDA has approved the combination of sotorasib with panitumumab for the treatment of KRAS G12C-mutated metastatic colorectal cancer (mCRC) in adult patients who received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

The companion diagnostic Therascreen KRAS RGQ PCR Kit developed by QIAGEN has also been approved to aid in the identification of patients who may be eligible for treatment with sotorasib plus panitumumab and whose tumors harbor KRAS G12C mutations.

This approval is based on positive results of the CodeBreaK300 trial, which demonstrated an improvement in progression-free survival (PFS) in patients administered the recommended dose of sotorasib 960 mg with panitumumab 6 mg/kg.

CodeBreaK 300 trial evaluated the efficacy of sotorasib plus panitumumab, and identified mutations in tumor samples using the Therascreen KRAS RGQ PCR Kit. A total of 160 patients were randomized 1:1:1 to undergo treatment with either sotorasib 960 mg orally once daily plus panitumumab 6 mg/kg intravenously every 2 weeks, sotorasib 240 mg orally once daily plus panitumumab 6 mg/kg intravenously every 2 weeks, or investigator’s choice of standard of care (SOC) trifluridine with tipiracil or regorafenib.

The primary endpoint was PFS as evaluated by blinded independent central review, and secondary endpoints included overall survival (OS), overall response rate (ORR), and duration of response (DOR).

CodeBreaK 300 was not statistically powered for OS, but the median PFS was 5.6 months (95% CI: 4.2, 6.3) in the sotorasib 960 mg/panitumumab arm, and 2 months (95% CI: 1.9, 3.9) in the SOC arm (HR 0.48 [95% CI: 0.3, 0.78] P=.005).

The final analysis of OS was not statistically significant. The ORR was 26% (95% CI: 15, 40) in the sotorasib 960 mg/panitumumab arm, and 0 (95% CI: 0, 7) in the SOC arm. The median DOR was 4.4 months (range: 1.9+, 6+) in the sotorasib 960 mg/panitumumab arm. The final PFS analysis of patients in the sotorasib 240 mg/panitumumab arm compared to the SOC arm was not statistically significant.

The most common treatment-related adverse events (TRAEs) (≥20%) for sotorasib 960 mg/panitumumab included rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. The most common grade 3-4 laboratory abnormalities in ≥2 patients were decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

Sotorasib 960 mg should be administered orally once daily with panitumumab 6 mg/kg as an intravenous infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued. The first dose of sotorasib should be administered before the first panitumumab infusion.