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

Regulatory approval: On Jan 16, 2025, the FDA approved sotorasib (Lumakras) with panitumumab (Vectibix) for adult patients with KRAS G12C-mutated metastatic colorectal cancer, as determined by an FDA-approved test, after prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. Approval was supported by CodeBreaK 300, where sotorasib 960 mg plus panitumumab improved PFS versus investigator’s choice SOC (trifluridine/tipiracil or regorafenib). A QIAGEN therascreen companion diagnostic was also approved.

FDA approval (Jan 16, 2025): sotorasib + panitumumab in KRAS G12C-mutated mCRC

The FDA approved sotorasib (Lumakras) with panitumumab (Vectibix) 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.

The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN) as a companion diagnostic to identify colorectal cancers harboring KRAS G12C mutations for potential eligibility.

Supporting trial: CodeBreaK 300 (NCT05198934)

  • Design: randomized, open-label, controlled; n=160, randomized 1:1:1.
  • Arms: sotorasib 960 mg PO daily + panitumumab 6 mg/kg IV q2w; sotorasib 240 mg + panitumumab; or investigator’s choice SOC (trifluridine/tipiracil or regorafenib).
  • Primary endpoint: PFS by blinded independent central review (RECIST v1.1).

Efficacy (960 mg sotorasib + panitumumab vs SOC)

  • Median PFS: 5.6 vs 2.0 months; HR 0.48 (95% CI 0.30–0.78), p=0.005.
  • ORR: 26% (95% CI 15–40) vs 0% (95% CI 0–7).
  • Median DOR: 4.4 months (range 1.9+ to 6+).
  • OS: final analysis not statistically significant; study not powered for OS.
  • The 240 mg sotorasib + panitumumab arm did not show a statistically significant PFS difference vs SOC.

Safety highlights (≥20% AEs; 960 mg combination)

Rash, dry skin, diarrhea, stomatitis, fatigue, musculoskeletal pain. Grade 3–4 lab abnormalities in ≥2 patients included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

Labeled dosing (from FDA communication)

Sotorasib 960 mg once daily; panitumumab 6 mg/kg IV every 14 days. The first sotorasib dose should be given before the first panitumumab infusion.

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