FDA Approves Vectibix® (Panitumumab) For Use In Wild-Type RAS Metastatic Colorectal Cancer

  • Vectibix Demonstrated an Improvement in Overall Survival in Patients With Wild-Type RAS Metastatic Colorectal Cancer
  • Predictive Biomarkers Allow Physicians to More Accurately Identify Treatments to Potentially Optimize Cancer Care
  • Approved Companion Diagnostic Tool Strengthens Precision Medicine Approach

THOUSAND OAKS, CA, USA I June 29, 2017 I Amgen (NASDAQ: AMGN) today announced that the U.S. Food and Drug Administration (FDA) has approved the 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, Calif. "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. 

About Colorectal Cancer
Colorectal cancer is the third most common cancer found in both men and women in the U.S., with approximately 135,000 new cases estimated to be diagnosed in 2017.1 Approximately 20 percent of colon cancers are diagnosed at the metastatic stage when the disease has already spread to distant organs, a diagnosis associated with only a 12 percent five-year survival rate.2 Using molecular approaches to identify unique genetic signatures in mCRC has the potential to help improve treatment outcomes.3

About the '0007 Study (NCT01412957)
This Phase 3 global, multicenter, randomized, open-label study was designed to evaluate OS with Vectibix and BSC compared to BSC alone in patients with chemorefractory wild-type KRAS (exon 2) mCRC.

The key efficacy analysis of the study showed that Vectibix plus BSC (n=189) was statistically significant to BSC alone (n=188). Patients with wild-type KRAS (exon 2) mCRC treated with Vectibix plus BSC achieved a median OS of 10 months compared to 7.4 months for patients treated with BSC alone (HR=0.73; 95 percent CI: 0.57, 0.93, p=0.0096). 

In patients with mutant RAS mCRC, no differences in OS or progression-free survival (PFS) were observed between the treatment arms [OS HR=0.99 (95 percent CI: 0.49, 2.00); PFS HR=1.03 (95 percent CI: 0.56, 1.90)].

No new safety signals were seen in the '0007 study. The safety profile was comparable to the known safety profile of Vectibix when administered as a single agent.

About the PRIME Study
PRIME was a randomized, Phase 3, open-label study of Vectibix and FOLFOX combination therapy versus FOLFOX monotherapy in 1,183 adults with untreated mCRC who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. The primary endpoints were PFS and OS.

The PRIME study showed that patients with wild-type KRAS tumors (exon 2) achieved statistically significant improvement in PFS with Vectibix and FOLFOX versus FOLFOX alone (9.6 versus 8.0 months [HR=0.80; 95 percent CI: 0.66, 0.97, p=0.02]) and a significant 4.4 month improvement in OS versus FOLFOX alone (23.8 versus 19.4 months [HR=0.82, 95 percent CI: 0.70, 0.98]).

Analyses from the PRIME study evaluated the treatment effect of Vectibix plus FOLFOX compared with FOLFOX alone in the wild-type RAS subgroup and found that Vectibix plus FOLFOX extended the prespecified major efficacy measure of PFS versus FOLFOX alone, 10.1 months versus 7.9 months, respectively (HR=0.72; 95 percent CI: 0.58, 0.90). The study demonstrated that the median OS for patients treated with Vectibix plus FOLFOX was 25.8 months versus 20.2 months for those treated with FOLFOX alone (HR=0.77; 95 percent CI: 0.64, 0.94). There were no OS or PFS benefit in Vectibix-treated patients with mutant RAS mCRC.

About the ASPECCT Study
ASPECCT was a global, randomized, multicenter, open-label, Phase 3 non-inferiority trial designed to compare the effect of Vectibix versus Erbitux® (cetuximab) on OS for monotherapy treatment of 1,010 patients with EGFR-expressing, chemorefractory wild-type KRAS (exon 2) mCRC.

The ASPECCT study met its primary endpoint of non-inferiority for improving OS in patients taking Vectibix (n=499) versus Erbitux (n=100) as a single agent for the treatment of mCRC in patients with wild-type KRAS tumors who have not responded to chemotherapy.  Patients treated with Vectibix demonstrated an OS of 10.4 months versus 10 months for patients treated with Erbitux  (HR=0.97; 95 percent CI: 0.84-1.11).

About Vectibix® (panitumumab) 
Vectibix is the first fully human monoclonal anti-EGFR antibody approved by the FDA for the treatment of mCRC. Vectibix was approved in the U.S. 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.

About Amgen's Commitment to Oncology
Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen's supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.

About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

SOURCE: Amgen

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