FDA

Sotorasib plus panitumumab OK’d for KRAS G12C-mutated colorectal cancer

January 22, 2025

Brand name: Lumakras; Vectibix

Generic name: sotorasib; panitumumab

Manufacturer: Amgen

Approval date: January 16, 2025

FDA approved Lumakras (sotorasib) with Vectibix (panitumumab) for adults with KRAS G12C-mutated metastatic colorectal cancer (mCRC), as determined by an FDA-approved test, who’ve received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

The agency also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device to aid in identifying patients with CRC whose tumors harbor KRAS G12C mutations and who may be eligible for the combination therapy.

Efficacy

Efficacy was evaluated in the phase 3, open-label CodeBreaK 300 trial (NCT05198934) involving 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 q2wks
• sotorasib 240 mg orally once daily and panitumumab 6 mg/kg IV q2wks
• investigator’s choice of standard of care (SOC) trifluridine/tipiracil or regorafenib

The major efficacy outcome was progression-free survival (PFS). Additional efficacy outcome measures included overall survival (OS), overall response rate (ORR), and duration of response (DOR). The study wasn’t 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 wasn’t 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 with the SOC arm wasn’t statistically significant.

Safety

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 lab abnormalities were hypomagnesemia, hypokalemia, hypocalcemia, and hyperkalemia.

Recommended dose

The recommended sotorasib dose is 960 mg orally once daily. The recommended panitumumab dose is 6 mg/kg administered as an IV infusion q2wks 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.

Sources:

FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer. Food and Drug Administration. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sotorasib-panitumumab-kras-g12c-mutated-colorectal-cancer

FDA approves Lumakras® (sotorasib) in combination with Vectibix® (panitumumab) for chemorefractory KRAS G12C-mutated metastatic colorectal cancer. Amgen. 2025. https://www.amgen.com/newsroom/press-releases/2025/01/fda-approves-lumakras-sotorasib-in-combination-with-vectibix-panitumumab-for-chemorefractory-kras-g12cmutated-metastatic-colorectal-cancer

Lumakras. Package insert. Amgen; 2025. Accessed January 20, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/214665s009lbl.pdf

Vectibix. Package insert. Amgen; 2025. Accessed January 20, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/125147s213lbl.pdf