FDA Approves Amgen's Colorectal Cancer Combo Therapy

Amgen's combination therapy of LUMAKRAS (sotorasib) and Vectibix (panitumumab) has been granted approval by the US Food and Drug Administration (FDA) for the treatment of adults with metastatic colorectal cancer (mCRC) that harbors the KRAS G12C mutation. This mutation is found in a small percentage, approximately 3% to 5%, of colorectal cancer cases. The new treatment is specifically developed for patients who have previously received chemotherapy that included fluoropyrimidine, oxaliplatin, and irinotecan but have not achieved desired outcomes.

The FDA's decision is based on the promising results from the Phase III CodeBreaK 300 clinical trial. This study illustrates that the combination of LUMAKRAS and Vectibix is the first targeted treatment pair to demonstrate superior efficacy in prolonging progression-free survival (PFS) when compared to the standard-of-care (SOC) treatments for chemorefractory KRAS G12C-mutated mCRC. Traditional SOC treatments in this context include medications like trifluridine/tipiracil or regorafenib.

The clinical trial involved 160 participants and tested two dosages of the LUMAKRAS and Vectibix combination against the physician's choice of SOC. The trial successfully met its primary goal by showing a substantial increase in progression-free survival. The median PFS for patients receiving the combination therapy was 5.6 months, significantly higher than the 2 months observed in those receiving the investigator's SOC.

The secondary endpoints of the study, which included overall survival (OS) and overall response rate (ORR), also showed favorable results for the combination therapy. The ORR was reported at 26%, indicating a noteworthy response among patients treated with the LUMAKRAS and Vectibix combination. The safety profile of the combination therapy was consistent with the known effects of its components, suggesting no unexpected adverse effects.

Jay Bradner, the executive vice-president of Amgen's research and development, emphasized the significance of this approval by stating, "LUMAKRAS plus Vectibix provides a targeted, biomarker-driven treatment option that effectively delays disease progression compared to current standards of care. This development reinforces our commitment to enhancing treatment outcomes for patients with advanced KRAS G12C-mutated metastatic colorectal cancer."

For effective administration of this therapy, it is crucial to identify the presence of the KRAS G12C mutation in patients through an FDA-approved biomarker test. This targeted approach aligns with the broader trend in oncology of using precision medicine to tailor treatments to the genetic profile of individual cancers.

In a previous milestone, Amgen secured FDA approval for LUMAKRAS in May 2021 for treating adults with locally advanced or metastatic non-small cell lung cancer that also features the KRAS G12C mutation. This success in lung cancer treatment paved the way for further exploration and eventual approval of the combination therapy for metastatic colorectal cancer, offering new hope for patients who have limited options after standard chemotherapy.