Tthe US Food and Drug Administration (FDA) has approved Amgen's supplemental Biologics License Application (sBLA) for Vectibix (panitumumab) for patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC) as first-line therapy in combination with Folfox and as monotherapy following disease progression after prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy. Vectibix is the first-and-only fully human monoclonal anti-epidermal growth factor receptor (EGFR) antibody approved by the FDA for this patient population.

As part of this new indication, the FDA approved the first multigene, next-generation sequencing-based test to identify the RAS mutation status of a patient's tumor. Next-generation sequencing is a novel diagnostics test technique that makes a more personalized medicine approach possible. This companion diagnostic helps physicians identify patients that are more likely to benefit from treatment with Vectibix.

"Of the few biomarkers in colorectal cancer, RAS mutation status provides actionable information when deciding on a first-line treatment option in mCRC patients," said Marwan G. Fakih, M.D., co-director of the Gastrointestinal Cancer Program at City of Hope, Duarte, California. "Panitumumab has demonstrated a significant overall survival benefit to patients whose mCRC does not have mutations in RAS, providing physicians with a novel targeted treatment option and allowing us to develop a personalized approach as we help patients fight this devastating disease."

The full approval for Vectibix as a treatment for patients with wild-type KRAS mCRC was based on results from the Phase 3 PRIME and ASPECCT trials. The approval of a refined indication for the treatment of patients with wild-type RAS mCRC was based on a retrospective analysis from the PRIME study and prospective, pre-defined analyses from the Phase 3 '0007 study. The '0007 study evaluated the efficacy of Vectibix plus best supportive care (BSC) versus BSC alone in patients with chemorefractory, wild-type KRAS mCRC. Data from a key secondary endpoint showed that patients with wild-type RAS (exons 2, 3, and 4 of KRAS and NRAS) mCRC treated with Vectibix plus BSC resulted in a statistically significant improvement in overall survival (OS) of 10 months compared to 6.9 months for patients treated with BSC alone (HR=0.70; 95 percent CI: 0.53, 0.93, p=0.0135). The safety profile of Vectibix in patients with wild-type RAS mCRC is consistent with that seen previously in patients with wild-type KRAS mCRC.

"Every patient with cancer is unique, and we are committed to utilizing cutting-edge science and technology to target treatments to the patients more likely to benefit," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "This approval for Vectibix reinforces the significance of biomarker testing as a treatment planning tool in metastatic colorectal cancer and further validates the potential for precision medicine to optimize patient outcomes."

Most common adverse reactions (= 20 percent) of Vectibix as monotherapy are skin rash with variable presentations, paronychia, fatigue, nausea and diarrhea. Most common adverse reactions (= 20 percent) with Vectibix plus Folfox are diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus and dry skin. The most common serious adverse reactions (= 2 percent difference between treatment arms) were diarrhea and dehydration.

Vectibix is the first fully human monoclonal anti-EGFR antibody approved by the FDA for the treatment of mCRC. Vectibix was approved in the US in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.

In May 2014, the FDA approved Vectibix for use in combination with Folfox, as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this approval, Vectibix became the first-and-only biologic therapy indicated for use with Folfox, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC for patients with wild-type KRAS mCRC.

In June 2017, the FDA approved a refined indication for Vectibix for use in in patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) mCRC.