Amgen announced that the U.S. Food and Drug Administration (FDA) has approved LUMAKRAS® (sotorasib) in combination with Vectibix® (panitumumab) for the treatment of 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. Approval is based on the pivotal Phase 3 CodeBreaK 300 study, which demonstrated that LUMAKRAS plus Vectibix is the first and only targeted treatment combination for chemorefractory KRAS G12C-mutated mCRC to show superior progression-free survival (PFS) compared to the investigated standard-of-care (SOC). The CodeBreaK 300 clinical trial compared LUMAKRAS at two different doses (960 mg daily or 240 mg daily) in combination with Vectibix to the investigator's choice of SOC (trifluridine and tipiracil or regorafenib) in patients with chemorefractory KRAS G12C-mutated mCRC. Study results demonstrated that LUMAKRAS 960 mg daily plus Vectibix (n=53) showed an improved median PFS of 5.6 months (4.2, 6.3) compared to 2 months (1.9, 3.9) on investigator's choice of care (n=54), with a hazard ratio (HR) of 0.48 (95% Confidence Interval [CI]: 0.3, 0.78) and a p-value of 0.005. The study demonstrated an improved overall response rate (ORR) of 26% (95% CI: 15, 40) compared to 0% with investigator's choice (95% CI: 0, 7).
The study was not statistically powered for overall survival (OS). The median overall survival (mOS) for patients treated with LUMAKRAS plus Vectibix was not reached (NR) (8.6, NR), and mOS for patients treated with investigator's choice was 10.3 months (7, NR), with a HR of 0.7 (95% CI: 0.41, 1.18); the final analysis of OS was not statistically significant. Safety profiles were consistent with those historically observed for LUMAKRAS and Vectibix. The most common adverse reactions (=20%) are rash (87%), dry skin (28%), diarrhea (28%), stomatitis (26%), fatigue (21%) and musculoskeletal pain (21%). PFS of LUMAKRAS 240 mg daily plus Vectibix (n=53) compared to investigator's choice was not statistically significant.
The KRAS G12C mutation is present in approximately 3-5% of colorectal cancers as determined by an FDA-approved biomarker test.3-5 This emphasizes the important role of comprehensive biomarker testing in mCRC. By detecting an actionable mutation, eligible patients are now able to receive a corresponding targeted therapy that may lead to improved responses.