Pfizer Inc. (NYSE:PFE) announced that the U.S. Food and Drug Administration (FDA) has accepted for review the Supplemental New Drug Applications (sNDAs) for BRAFTOVI® (encorafenib) + MEKTOVI® (binimetinib) for patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test.
The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in Fourth-Quarter 2023 for the sNDAs. In the U.S., BRAFTOVI + MEKTOVI is currently approved for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test. BRAFTOVI is also approved, in combination with cetuximab, for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy.
"For more than a decade, Pfizer Oncology has been at the forefront of bringing biomarker-driven treatment options to patients with cancer. Since their initial regulatory approvals, BRAFTOVI and MEKTOVI have helped improve outcomes in their respective indications of BRAF-mutated metastatic melanoma and BRAF-mutated metastatic colorectal cancer," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology and Rare Disease, Pfizer Global Product Development. "Through our comprehensive development program, the BRAFTOVI and MEKTOVI combination has shown the potential to help more patients, such as those living with BRAF V600E-mutant non-small cell lung cancer. These sNDAs build on Pfizer's long heritage of meeting the diverse needs of people with NSCLC, and we look forward to working with the FDA on their review of these applications."
These sNDAs are supported by results from the PHAROS trial (NCT03915951), an open-label, multicenter, non-randomized, Phase 2 study (n=98) to determine the safety, tolerability, and efficacy of BRAFTOVI given in combination with MEKTOVI in patients with BRAF V600E-mutant metastatic NSCLC. PHAROS met its primary endpoint of objective response rate. Detailed results from the PHAROS study will be presented at an upcoming scientific congress.
About Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the second most common type of cancer and the number one cause of cancer-related death around the world.(1) In 2023, the American Cancer Society estimates there will be about 238,340 new cases of lung cancer diagnosed in the U.S.(2) NSCLC accounts for approximately 80-85% of all lung cancers.(3)Some lung cancers are linked to acquired genetic abnormalities. For instance, a BRAF V600E mutation occurs in approximately 2% of NSCLC cases4 and stimulates tumor cell growth and proliferation by altering the MAP kinase (MAPK) signaling pathway. Targeting components of this pathway could potentially inhibit unchecked tumor growth and proliferation caused by BRAF mutations.(5)
Precision medicine is increasingly being developed for NSCLC patients with genetic changes, such as BRAF mutations, that can be detected using biomarker tests.(6,7) Advances in targeted therapy have been associated with significant improvements in population-level NSCLC mortality in recent years.(8)
About PHAROS
PHAROS (NCT03915951) is an open-label, multicenter, non-randomized, Phase 2 study to determine the safety, tolerability, and efficacy of BRAFTOVI given in combination with MEKTOVI in 98 patients with BRAF V600E-mutant metastatic NSCLC. The primary endpoint is objective response rate, based on independent radiologic review (per RECIST v1.1); secondary objectives will evaluate additional efficacy endpoints and safety. Duration of response is a key secondary endpoint. The trial is conducted across 53 sites in: Italy (5 sites), the Netherlands (2 sites), South Korea (3 sites), Spain (4 sites), and the U.S. (39 sites).
About BRAFTOVI + MEKTOVI
BRAFTOVI is an oral small molecule BRAF kinase inhibitor and MEKTOVI is an oral small molecule MEK inhibitor which target key proteins in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of this pathway has been shown to occur in many cancers, including melanoma, CRC, and NSCLC.In 2018, the FDA approved BRAFTOVI + MEKTOVI in combination for patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test. The approval was based on COLUMBUS, a randomized, active-controlled, open-label, Phase 3 trial.
In 2020, BRAFTOVI was FDA-approved, in combination with cetuximab, for the treatment of adults with metastatic CRC with a BRAF V600E mutation, as detected by an FDA-approved test. The approval was based on results from the BEACON CRC trial.
Pfizer has exclusive rights to BRAFTOVI and MEKTOVI in the U.S., Canada, and all countries in the Latin America, Africa, and Middle East regions. Ono Pharmaceutical Co. Ltd. has exclusive rights to commercialize both products in Japan and South Korea, Medison has exclusive rights in Israel, and Pierre Fabre has exclusive rights in all other countries, including Europe and Asia-Pacific (excluding Japan and South Korea).
Please see full Prescribing Information for BRAFTOVI and full Prescribing Information for MEKTOVI.
About Pfizer Oncology
At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference in the lives of people living with cancer. Today, we have an industry-leading portfolio of 24 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, genitourinary, colorectal, blood and lung cancers, as well as melanoma.
About Pfizer: Breakthroughs That Change Patients' Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us.
1. World Health Organization. International Agency for Research on Cancer. GLOBOCAN 2020: Lung cancer fact sheet. Updated December 2020. Accessed February 2, 2023. http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf
2. American Cancer Society. Key statistics for lung cancer. Updated February 14, 2022. Accessed February 2, 2023. https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html
3. American Cancer Society. What is lung cancer? Updated October 1, 2019. Accessed February 2, 2023. https://www.cancer.org/cancer/lung-cancer/about/what-is.html
4. American Lung Association. BRAF and lung cancer. Updated November 17, 2022. Accessed February 2, 2023. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/braf
5. Lieu CH, Corcoran RB, Overman MJ. Integrating biomarkers and targeted therapy into colorectal cancer management. Am Soc Clin Oncol Educ Book. 2019;39:207-215. doi: 10.1200/EDBK_240839
6. Planchard D, Popat S, Kerr K, et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018;29(Suppl. 4), iv192-iv237. doi:10.1093/annonc/mdy275
7. König D, Savic Prince S, Rothschild SI. Targeted therapy in advanced and metastatic non-small cell lung cancer. An update on treatment of the most important actionable oncogenic driver alterations. Cancers. 2021;13(4), 804. doi:10.3390/cancers13040804
8. Howlader N, Forjaz G, Mooradian MJ, et al. The effect of advances in lung-cancer treatment on population mortality. N Engl J Med. 2020;383(7), 640–649. doi:10.1056/NEJMoa1916623