FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer

On January 16, 2025, the Food and Drug Administration approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for adult patients with KRAS G12C-mutated metastatic colorectal cancer (mCRC), as determined by an FDA-approved test, who have received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

Today, the FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device to aid in identifying patients with colorectal cancer whose tumors harbor KRAS G12C mutations and who may be eligible for Lumakras with Vectibix.

Full prescribing information for Lumakras and Vectibix will be posted on Drugs@FDA.

Efficacy and Safety

Efficacy was evaluated in CodeBreaK 300 (NCT05198934), a randomized, open-label, controlled trial in patients with KRAS G12C-mutated mCRC who previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. Mutations were prospectively identified in tumor tissue samples using the QIAGEN therascreen KRAS RGQ PCR kit. A total of 160 patients were randomized (1:1:1) to receive either sotorasib 960 mg orally once daily and panitumumab 6 mg/kg IV every 2 weeks, sotorasib 240 mg orally once daily and panitumumab 6 mg/kg IV every 2 weeks, or investigator’s choice of standard of care (SOC) trifluridine/tipiracil or regorafenib.

The major efficacy outcome measure was progression-free survival (PFS) as evaluated by blinded independent central review according to RECIST v1.1. Additional efficacy outcome measures included overall survival (OS), overall response rate (ORR), and duration of response (DOR). The study was not statistically powered for OS. 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 (hazard ratio 0.48 [95% CI: 0.3, 0.78] 2-sided p-value 0.005). The final analysis of OS was not statistically significant. ORR was 26% (95% CI: 15, 40) in the sotorasib 960 mg/panitumumab arm and 0 (95% CI: 0, 7) in the SOC arm. Median DOR was 4.4 months (range: 1.9+, 6+) in the sotorasib 960 mg/panitumumab arm.

The final analysis of PFS for patients randomized to the sotorasib 240 mg/panitumumab arm compared to the SOC arm was not statistically significant.

The most common adverse reactions (≥20%) for sotorasib 960 mg/panitumumab were 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.

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

This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Expedited Programs

This application was granted orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

Follow the Oncology Center of Excellence on X: @FDAOncology.