CASTRES, France, Nov. 3, 2023 /PRNewswire/ -- Pierre Fabre Laboratories today announced that the European Medicines Agency (EMA) has approved the submission of BRAFTOVI® (encorafenib) MEKTOVI® (binimetinib) for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with BRAFV600 mutation, with or without prior treatment.
The request is based on the results of the PHAROS registry study,1 which, according to an independent review, demonstrated an objective response rate (OR) of 75% in untreated patients, with 59% maintaining response for at least 12 months, and 46% in patients with previous treatment.1
"Lung cancer is the leading cause of cancer death worldwide,2 and there are currently limited effective treatment options for patients with advanced NSCLC with BRAFV600 mutation." Eric Ducournau, CEO of Pierre Fabre Laboratories: "With our strategic focus on lung cancer and oncology precision medicine, this presents a clinically significant change to oncology patient populations with high unmet needs.
The phase 2 PHAROS1 trial demonstrated that one daily dose of 450 mg of BRAFTOVI® and two daily doses of 45 mg of MEKTOVI®1 provided significant clinical benefit for these patients with an objective response rate (OR) of 75% (CI 95%: 62, 85) in treatment-naïve patients (n=59), and 59% of them maintained a response for at least 12 months. For patients who had received prior treatment (n=39), OR was 46% (95% CI: 30, 63), and response was 33% for at least 12 months. Median progression-free survival (PFS) was not reached at data cut-off for the untreated group (95% CI: 15.7, NE) and 9.3 months (95% CI: 6.2, NE). ) for the group with previous treatment. Median overall survival (OS) was not reached for any of the subgroups at the time of data cutoff. The most common treatment-related adverse events observed in the PHAROS trial were nausea (50%), diarrhea (43%), fatigue (32%), and vomiting (29%).
These findings were simultaneously published in the Journal of Clinical Oncology and presented at the American Society of Clinical Oncology (ASCO) meeting on June 4, 2023.1
BRAFTOVI® MEKTOVI® are currently approved in Europe for the treatment of adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation.3,4 BRAFTOVI® in combination with cetuximab is also approved in Europe for the treatment of adult patients with metastatic colorectal cancer. (mCRC) with a BRAFV600E mutation with prior systemic therapy.3
PHAROS (NCT03915951) is an ongoing, open-label, multicenter, non-randomized Phase 2 study to determine the efficacy and safety of BRAFTOVI® MEKTOVI® in 98 patients with metastatic NSCLC with BRAFV600E mutation. Mutations were identified by next-generation sequencing or polymerase chain reaction testing performed at the patient's local laboratory. The primary endpoint is confirmed RO according to RECIST v1.1, by independent radiological review (IRR); Secondary objectives include additional efficacy objectives such as duration of response (DR), PFS and OS, as well as safety. The trial is carried out in 56 centers in: Italy, the Netherlands, South Korea, Spain and the United States.
The PHAROS trial is sponsored by Pfizer Inc. and is conducted with the support of Pierre Fabre Laboratories.
About BRAF-mutated advanced non-small cell lung cancer (NSCLC)
Lung cancer is the second most common type of cancer and the leading cause of cancer death in the world.2 NSCLC represents approximately 80-85% of all lung cancers.5
Some lung cancers are due to acquired genetic abnormalities, such as the BRAF mutation. The use of biomarkers to identify a person's specific type of tumor allows treatment to be personalized and made more effective, since the molecular composition of the cancer usually determines the response to different therapies.
BRAF mutations occur in approximately 3-5% of NSCLC cases.1 It stimulates the growth and proliferation of tumor cells by altering the MAP kinase (MAPK) signaling pathway. Action on the components of this pathway could inhibit uncontrolled tumor growth and proliferation caused by BRAF mutations.1,6
Precision medicine is increasingly being developed for NSCLC patients with genetic changes, such as BRAF mutations, that can be detected by biomarker testing.7,8 Advances in targeted therapy and the more widespread use of biomarker testing are have been associated with significant improvements in mortality from NSCLC at the population level in recent years.9
About BRAFTOV® MEKTOV®
BRAFTOVI® (encorafenib) is an oral small-molecule BRAF kinase inhibitor and MEKTOVI® (binimetinib) is an oral small-molecule MEK inhibitor, both targeting key proteins of the MAPK (RAS-RAF-MEK-ERK) signaling pathway. ). Uncontrolled activation of this pathway has been shown to occur in many types of cancer, including melanoma, CRC, and NSCLC.1
In 2018, the European Commission (EC) approved BRAFTOVI® MEKTOVI® for adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation. The approval was based on the results of the randomized, active-controlled, open-label, multicenter phase 3 COLUMBUS trial.
In 2020, BRAFTOVI® was approved by the EC, in combination with cetuximab, for the treatment of adults with metastatic CRC with a BRAFV600E mutation. The approval was based on the results of the randomized, active-controlled, open-label, multicenter phase 3 BEACON CRC trial.
Pfizer has exclusive rights to market BRAFTOVI® and MEKTOVI® in the US, Canada and all countries in the Latin America, Africa and Middle East regions. Ono Pharmaceutical Co., Ltd. has exclusive rights to market both products in Japan and South Korea, Medison has exclusive rights in Israel, and Pierre Fabre Laboratories in all other countries, including Europe and Asia-Pacific.
Complete product and safety information for the use of BRAFTOVI® and MEKTOVI® is contained in the Summary of Product Characteristics (SPC), published in the European Public Assessment Report (EPAR) and available in all official languages. The EU. The Summary of Product Characteristics can be consulted at: https://www.ema.europa.eu/en
About Pierre Fabre Laboratories
Pierre Fabre Laboratories is a leading French medical and care company with 4 decades of experience in innovation, development, manufacturing and marketing in the oncology sector. The company dedicated nearly 80% of its R&D spending to oncology in 2022 and recently declared targeted therapies as its top R&D priority. Its current commercial portfolio in oncology spans colorectal, breast and lung cancers, melanoma, hematology and precancerous skin conditions such as actinic keratosis.
In 2022, Pierre Fabre Laboratories had a turnover of €2.7 billion, 69% of which came from international sales in 120 countries. Established in the south-west of France since its creation in 1962, the Group manufactures more than 90% of its products in France and employs around 9,600 people worldwide. The company is 86% owned by the Pierre Fabre Foundation, a public interest foundation recognized by the government, and secondarily by its own employees through an international employee share plan. Pierre Fabre Laboratories' sustainability policy has been evaluated by the certification body AFNOR at the "Exemplary" level of its CSR label (ISO 26 000 standard for sustainable development).
More information about Pierre Fabre Laboratories can be found at www.pierre-fabre.com, @PierreFabre.
1 Riely GJ, Smit EF, Ahn MJ. Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non–Small-Cell Lung Cancer. Journal of Clinical Oncology.2023;41:21,3700-3711.
2 World Health Organization. International Agency for Research on Cancer. GLOBOCAN 2020: Lung Cancer Fact Sheet. Available at: //gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Last access: July 2023.
3 European Medicines Agency. BRAFTOVI® (encorafenib) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/medicines/h.... Last access: July 2023.
4 European Medicines Agency. MEKTOVI® (binimetinib) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/medicines/h.... Last access: July 2023.
5 American Cancer Society. What is lung cancer? Available at: https://www.cancer.org/cancer/lung-cancer/about/what-is.html. Last access: July 2023.
6 Yan N, Guo S, Zhang H, et al. BRAF-Mutated Non-Small Cell Lung Cancer: Current Treatment Status and Future Perspective. Front Oncol. 2022;12:863043. doi: 10.3389/fonc.2022.863043.
7 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.
8 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.
9 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.
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