BRAFTOVI + MEKTOVI now gives adult patients with BRAF V600E-mutant metastatic non-small cell lung cancer a new personalized treatment option
NEW YORK, NY, USA I October 12, 2023 I Pfizer Inc. (NYSE: PFE) announced today that the U.S. Food and Drug Administration (FDA) has approved BRAFTOVI® (encorafenib) + MEKTOVI® (binimetinib) for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test.1BRAF V600Emutations can be assessed from either plasma or tumor tissue using the FoundationOne Liquid CDx or the FoundationOne CDx FDA-approved companion diagnostic tests, respectively.
“Today’s approval builds on our long-standing commitment to deliver innovative, personalized medicines to patients with lung cancer. By pursuing precision medicines that target a patient’s specific type of cancer, we are leveraging our deep understanding of tumor biology to help address the underlying cause of disease,” said Chris Boshoff, M.D., Ph.D., Chief Oncology Research and Development Officer and Executive Vice President at Pfizer. “Since its initial FDA approval in 2018, BRAFTOVI + MEKTOVI combination therapy has helped thousands of people living with BRAF V600E- or V600K-mutant unresectable or metastatic melanoma.2 We look forward to helping even more patients with our BRAFTOVI + MEKTOVI targeted combination therapy.”
The FDA’s approval is based on data from the ongoing Phase 2 PHAROS clinical trial (NCT03915951), an open-label, multicenter, single‑arm study examining BRAFTOVI + MEKTOVI combination therapy in both treatment-naïve and previously treated patients with BRAF V600E-mutant metastatic NSCLC.
“BRAF V600E mutations identify a unique subtype of metastatic non-small cell lung cancer that presents an actionable biomarker that precision medicines like BRAFTOVI + MEKTOVI combination therapy can help address,” said Gregory Riely, M.D., Ph.D., Vice Chair, Clinical Research in the Department of Medicine at Memorial Sloan Kettering Cancer Center (MSK) and PHAROS investigator. “The PHAROS trial demonstrated that these patients could benefit from BRAFTOVI + MEKTOVI targeted therapy regardless of their prior treatment history. Given the specific efficacy and safety profile, patients and providers now have another option to help personalize treatment plans based on individual risk factors and preferences.”
The PHAROS study met its major efficacy outcome measures of objective response rate (ORR), as assessed by independent review committee (IRC), and duration of response (DOR) in both treatment groups. For treatment-naïve patients (n=59), ORR was 75% (95% CI: 62, 85), and 59% of the patients responded for at least 12 months. Median DOR was not estimable (NE) for this group at the time of data cutoff. For previously treated patients (n=39), ORR was 46% (95% CI: 30, 63), and 33% of the patients responded for at least 12 months. Median DOR was 16.7 months (95% CI: 7.4, NE). These data were presented earlier this year at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the Journal of Clinical Oncology
(JCO).3
The most common (≥25%) all-causality adverse reactions observed in the PHAROS trial were fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, and cough. A total of 17% of patients experienced an adverse reaction that resulted in permanent discontinuation of MEKTOVI and 16% experienced an adverse event that resulted in permanent discontinuation of BRAFTOVI. Serious adverse reactions occurred in 38% of patients. Serious adverse reactions occurring in ≥2% of patients included hemorrhage (6%), diarrhea (4.1%), anemia, dyspnea, pneumonia (3.1% each), arrhythmia, device-related infection, edema, myocardial infarction, and pleural effusion (2% each). Fatal adverse reactions occurred in 2% of patients, including intracranial hemorrhage and myocardial infarction (1% each).
BRAFTOVI + MEKTOVI is also FDA-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 FDA-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.
Pfizer has exclusive rights to BRAFTOVI and MEKTOVI in the U.S., Canada, and all countries in Latin America, Africa, and the Middle East. 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).
The PHAROS trial is conducted with support from Pierre Fabre.
About BRAF V600E-mutant 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.4 NSCLC accounts for approximately 80-85% of all lung cancers.5
Certain lung cancers are linked to acquired genetic abnormalities like a BRAF V600E mutation. By using biomarkers to identify a person’s particular tumor type, treatment can become more personalized and effective, since the molecular makeup of a person’s cancer often determines how they respond to different therapies.
A BRAF V600E mutation occurs in approximately 2% of NSCLC cases.6 It stimulates tumor cell growth and proliferation by altering the MAP kinase (MAPK) signaling pathway. Targeting components of this pathway could potentially help inhibit tumor growth and proliferation caused by BRAF mutations.7
Precision medicine is increasingly being developed for NSCLC patients with genetic changes, such as BRAF mutations, that can be detected using biomarker tests.8,9 In recent years, more widespread use of biomarker testing and targeted therapies have been associated with improvements in population-level NSCLC mortality.10
INDICATIONS AND USAGE
BRAFTOVI® (encorafenib) and MEKTOVI® (binimetinib) are kinase inhibitors indicated for use in combination 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 indicated, 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.
BRAFTOVIand MEKTOVI are kinase inhibitors indicated for use in combination for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test.
Limitations of Use: BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma, wild-type BRAF CRC, or wild-type BRAF NSCLC.
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. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
1 BRAFTOVI® (encorafenib) Prescribing Information. Array BioPharma, Inc. (a wholly owned subsidiary of Pfizer Inc.): 2023.
2 Data on File Pfizer March 2022 (REF-BMK0842 + REF-BMK1009)
3 Riely GJ, Smit EF, Ahn MJ, et al. Phase II, open-label study of encorafenib plus binimetinib in patients with BRAF V600-mutant metastatic non–small-cell lung cancer. Journal of Clinical Oncology; 41(21): 3700-3711. doi: 10.1200/JCO.23.00774
4 World Health Organization. International Agency for Research on Cancer. GLOBOCAN 2020: Lung cancer fact sheet. Updated December 2020. Accessed August 16, 2023. http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf
5 American Cancer Society. What is lung cancer? Updated October 1, 2019. Accessed August 16, 2023. https://www.cancer.org/cancer/lung-cancer/about/what-is.html
6 American Lung Association. BRAF and lung cancer. Updated November 17, 2022. Accessed August 16, 2023. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/braf
7 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
8 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
9 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
10 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
SOURCE: Pfizer
Post Views: 152
BRAFTOVI + MEKTOVI now gives adult patients with BRAF V600E-mutant metastatic non-small cell lung cancer a new personalized treatment option
NEW YORK, NY, USA I October 12, 2023 I Pfizer Inc. (NYSE: PFE) announced today that the U.S. Food and Drug Administration (FDA) has approved BRAFTOVI® (encorafenib) + MEKTOVI® (binimetinib) for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test.1BRAF V600Emutations can be assessed from either plasma or tumor tissue using the FoundationOne Liquid CDx or the FoundationOne CDx FDA-approved companion diagnostic tests, respectively.
“Today’s approval builds on our long-standing commitment to deliver innovative, personalized medicines to patients with lung cancer. By pursuing precision medicines that target a patient’s specific type of cancer, we are leveraging our deep understanding of tumor biology to help address the underlying cause of disease,” said Chris Boshoff, M.D., Ph.D., Chief Oncology Research and Development Officer and Executive Vice President at Pfizer. “Since its initial FDA approval in 2018, BRAFTOVI + MEKTOVI combination therapy has helped thousands of people living with BRAF V600E- or V600K-mutant unresectable or metastatic melanoma.2 We look forward to helping even more patients with our BRAFTOVI + MEKTOVI targeted combination therapy.”
The FDA’s approval is based on data from the ongoing Phase 2 PHAROS clinical trial (NCT03915951), an open-label, multicenter, single‑arm study examining BRAFTOVI + MEKTOVI combination therapy in both treatment-naïve and previously treated patients with BRAF V600E-mutant metastatic NSCLC.
“BRAF V600E mutations identify a unique subtype of metastatic non-small cell lung cancer that presents an actionable biomarker that precision medicines like BRAFTOVI + MEKTOVI combination therapy can help address,” said Gregory Riely, M.D., Ph.D., Vice Chair, Clinical Research in the Department of Medicine at Memorial Sloan Kettering Cancer Center (MSK) and PHAROS investigator. “The PHAROS trial demonstrated that these patients could benefit from BRAFTOVI + MEKTOVI targeted therapy regardless of their prior treatment history. Given the specific efficacy and safety profile, patients and providers now have another option to help personalize treatment plans based on individual risk factors and preferences.”
The PHAROS study met its major efficacy outcome measures of objective response rate (ORR), as assessed by independent review committee (IRC), and duration of response (DOR) in both treatment groups. For treatment-naïve patients (n=59), ORR was 75% (95% CI: 62, 85), and 59% of the patients responded for at least 12 months. Median DOR was not estimable (NE) for this group at the time of data cutoff. For previously treated patients (n=39), ORR was 46% (95% CI: 30, 63), and 33% of the patients responded for at least 12 months. Median DOR was 16.7 months (95% CI: 7.4, NE). These data were presented earlier this year at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the Journal of Clinical Oncology
(JCO).3
The most common (≥25%) all-causality adverse reactions observed in the PHAROS trial were fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, and cough. A total of 17% of patients experienced an adverse reaction that resulted in permanent discontinuation of MEKTOVI and 16% experienced an adverse event that resulted in permanent discontinuation of BRAFTOVI. Serious adverse reactions occurred in 38% of patients. Serious adverse reactions occurring in ≥2% of patients included hemorrhage (6%), diarrhea (4.1%), anemia, dyspnea, pneumonia (3.1% each), arrhythmia, device-related infection, edema, myocardial infarction, and pleural effusion (2% each). Fatal adverse reactions occurred in 2% of patients, including intracranial hemorrhage and myocardial infarction (1% each).
BRAFTOVI + MEKTOVI is also FDA-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 FDA-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.
Pfizer has exclusive rights to BRAFTOVI and MEKTOVI in the U.S., Canada, and all countries in Latin America, Africa, and the Middle East. 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).
The PHAROS trial is conducted with support from Pierre Fabre.
About BRAF V600E-mutant 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.4 NSCLC accounts for approximately 80-85% of all lung cancers.5
Certain lung cancers are linked to acquired genetic abnormalities like a BRAF V600E mutation. By using biomarkers to identify a person’s particular tumor type, treatment can become more personalized and effective, since the molecular makeup of a person’s cancer often determines how they respond to different therapies.
A BRAF V600E mutation occurs in approximately 2% of NSCLC cases.6 It stimulates tumor cell growth and proliferation by altering the MAP kinase (MAPK) signaling pathway. Targeting components of this pathway could potentially help inhibit tumor growth and proliferation caused by BRAF mutations.7
Precision medicine is increasingly being developed for NSCLC patients with genetic changes, such as BRAF mutations, that can be detected using biomarker tests.8,9 In recent years, more widespread use of biomarker testing and targeted therapies have been associated with improvements in population-level NSCLC mortality.10
INDICATIONS AND USAGE
BRAFTOVI® (encorafenib) and MEKTOVI® (binimetinib) are kinase inhibitors indicated for use in combination 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 indicated, 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.
BRAFTOVIand MEKTOVI are kinase inhibitors indicated for use in combination for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test.
Limitations of Use: BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma, wild-type BRAF CRC, or wild-type BRAF NSCLC.
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. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
1 BRAFTOVI® (encorafenib) Prescribing Information. Array BioPharma, Inc. (a wholly owned subsidiary of Pfizer Inc.): 2023.
2 Data on File Pfizer March 2022 (REF-BMK0842 + REF-BMK1009)
3 Riely GJ, Smit EF, Ahn MJ, et al. Phase II, open-label study of encorafenib plus binimetinib in patients with BRAF V600-mutant metastatic non–small-cell lung cancer. Journal of Clinical Oncology; 41(21): 3700-3711. doi: 10.1200/JCO.23.00774
4 World Health Organization. International Agency for Research on Cancer. GLOBOCAN 2020: Lung cancer fact sheet. Updated December 2020. Accessed August 16, 2023. http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf
5 American Cancer Society. What is lung cancer? Updated October 1, 2019. Accessed August 16, 2023. https://www.cancer.org/cancer/lung-cancer/about/what-is.html
6 American Lung Association. BRAF and lung cancer. Updated November 17, 2022. Accessed August 16, 2023. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/braf
7 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
8 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
9 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
10 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
SOURCE: Pfizer
Post Views: 152
