437TiP Trial in progress: A phase III global study of sotorasib, a specific KRAS G12C inhibitor, in combination with panitumumab versus investigator’s choice in chemorefractory metastatic colorectal cancer (CodeBreaK 300)

Abstract

Sotorasib selectively and irreversibly inhibits the Kirsten rat sarcoma (KRAS) G12C mutant protein. This inhibition can result in accumulation of activated epidermal growth factor receptor (EGFR), which may drive resistance to sotorasib. Therefore, the combination of sotorasib with an EGFR inhibitor, such as panitumumab, might lead to more complete inhibition of tumor cell growth and survival. Early data for the combination of sotorasib and panitumumab from CodeBreaK 101 subprotocol H showed promising antitumor activity in chemorefractory metastatic colorectal cancer (mCRC). The objective of the current study is to evaluate whether the combination of sotorasib and panitumumab is superior to standard of care trifluridine/tipiracil or regorafenib in the setting of chemorefractory mCRC. CodeBreaK 300 (NCT05198934) is a global phase III randomized, open-label, active-controlled study of the efficacy and safety of oral sotorasib combined with intravenous panitumumab in patients with mCRC. Key eligibility criteria include mCRC with KRAS G12C mutation confirmed by central molecular testing of tumor biopsy, and at least 1 prior line of therapy. Patients must have received and progressed or experienced disease recurrence on or after fluoropyrimidine, irinotecan, and oxaliplatin given for metastatic disease unless ineligible in the opinion of the investigator. Approximately 153 patients will be enrolled and randomized 1:1:1 to receive either sotorasib 960 mg daily and panitumumab or sotorasib 240 mg daily and panitumumab or investigator’s choice (trifluridine and tipiracil, or regorafenib). The primary endpoint is progression-free survival using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by Blinded Independent Central Review (BICR). Key secondary endpoints include overall survival and objective response. Global enrollment is ongoing. NCT05198934. Medical writing support was provided by Tim Harrison, PharmD (Amgen Inc.). Amgen Inc.