A Phase 3 Multicenter, Randomized, Open-label,Active-controlled Study of Sotorasib and Panitumumab Versus Investigator’s Choice (Trifluridine and Tipiracil, or Regorafenib) for the Treatment of Previously Treated Metastatic Colorectal Cancer Subjects with KRAS p.G12C Mutation
The aim of the study is to compare progression-free survival (PFS) in previously treated participants with Kirsten rat sarcoma (KRAS) p.G12C mutated colorectal cancer (CRC) receiving sotorasib 240 mg once daily (QD) and panitumumab vs investigator’s choice (trifluridine and tipiracil, or regorafenib), and sotorasib 960 mg once daily (QD) and panitumumab vs investigator’s choice (trifluridine and tipiracil, or regorafenib).
- Pathologically documented metastatic colorectal adenocarcinoma with Kirsten rat sarcoma (KRAS) p.G12C mutation as determined by central testing.
- Participants will have received at least 1 prior line of therapy for metastatic disease. Participants must have received and progressed or experienced disease recurrence on or after fluoropyrimidine, irinotecan, and oxaliplatin given for metastatic disease unless the participant, in the opinion of the investigator, is not a candidate for fluoropyrimidine, irinotecan, or oxaliplatin, in which case, the participant may be eligible after investigator discussion with Amgen medical monitor provided participant has received at least one prior line of therapy for metastatic disease and provided trifluridine and tipiracil or regorafenib is deemed the appropriate next line of therapy for the participant.
- Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Lesions previously radiated are not considered measurable unless they have progressed after radiation.Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2.
- Life expectancy of >3 months, in the opinion of the investigator.
- Adequate hematologic and end-organ function, defined as the following within 10 days prior to randomization:
- Absolute neutrophil count (ANC) ≥1.5 x 10^9/L (without granulocyte colony stimulating factor support within 2 weeks of laboratory test used to determine eligibility).
- Hemoglobin ≥9.0 g/dL (without transfusion within 2 weeks of laboratory test used to determine eligibility).
- Platelet count ≥100 x 10^9/L (without transfusion within 2 weeks of laboratory test used to determine eligibility).
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times the upper limit of normal (ULN).
- Serum bilirubin ≤1.0 x ULN. For participants with Gilbert’s disease, direct bilirubin ≤1.0 x ULN.
- International normalized ratio (INR) and activated partial thromboplastin time (or partial thromboplastin time) ≤1.5 x ULN. Prothrombin time (PT) ≤1.5 x ULN may be used instead of INR for sites whose labs do not report INR.
- Estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation ≥30 mL/min/1.73 m^2.
□ Fridericia’s Correction Formula (QTcF) ≤470 msec.