FDA Approves Lumakras and Vectibix Combo for KRAS G12C-Mutated Metastatic Colorectal Cancer

Amgen, a leading biotechnology company, has announced the approval of a new combination therapy for a specific type of metastatic colorectal cancer (mCRC) by the U.S. Food and Drug Administration (FDA). The combination involves LUMAKRAS® (sotorasib) and Vectibix® (panitumumab) and is targeted at adult patients with KRAS G12C-mutated mCRC who have undergone prior treatment with specific chemotherapy regimens. This approval is significant as it marks the first and only targeted therapy for this specific patient group that has demonstrated a notable improvement in progression-free survival (PFS) compared to the standard-of-care (SOC).

Colorectal cancer is a major health concern, being the third leading cause of cancer-related deaths in the United States. The survival rate for patients diagnosed with metastatic disease is grim, with fewer than 20% surviving beyond five years post-diagnosis. Dr. Jay Bradner, Amgen's executive vice president of Research and Development, highlighted the importance of this new treatment combination, emphasizing its ability to delay disease progression more effectively than existing SOC treatments.

The pivotal Phase 3 CodeBreaK 300 trial served as the foundation for this approval. The study involved comparing two different doses of LUMAKRAS (960 mg and 240 mg daily), each in combination with Vectibix, against the investigator's choice of SOC, which included treatments like trifluridine/tipiracil or regorafenib. The trial revealed that the higher dose of LUMAKRAS, when combined with Vectibix, resulted in a PFS of 5.6 months compared to just 2 months with SOC. Additionally, the combination therapy achieved a 26% overall response rate, significantly outperforming the 0% recorded with SOC.

The safety profile of the combination therapy was consistent with known effects of the individual drugs, with common adverse reactions being rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. While the PFS improvement with the lower LUMAKRAS dose was not statistically significant, the 960 mg dose demonstrated clear benefits.

KRAS mutations are among the most common genetic alterations in colorectal cancer, and the KRAS G12C mutation specifically occurs in approximately 3-5% of cases. This highlights the critical role of biomarker testing to identify patients who could benefit from targeted therapies like LUMAKRAS and Vectibix. Dr. Marwan G. Fakih, one of the primary investigators of the study, noted that KRAS mutations historically predict worse outcomes in colorectal cancer, making this new treatment option a significant advancement for affected patients.

Michael Sapienza, CEO of the Colorectal Cancer Alliance, expressed optimism about the new combination therapy, recognizing it as a breakthrough for patients with KRAS G12C-mutated mCRC. Given the aggressive nature of this cancer and the limited treatment options available, the approval of LUMAKRAS with Vectibix marks a critical step forward in precision medicine and targeted cancer therapy.

The CodeBreaK 300 trial involved 160 participants and confirmed the combination's efficacy over SOC, meeting its primary endpoint of improved PFS. Even though the trial was not statistically powered for overall survival, the combination therapy showed favorable trends in survival outcomes.

In conclusion, Amgen's new combination of LUMAKRAS and Vectibix represents a significant advancement in the treatment of KRAS G12C-mutated metastatic colorectal cancer. As the first approved targeted therapy for this specific patient population, it offers hope for improved outcomes in a challenging and historically difficult-to-treat cancer subset.