On November 2, 2023 Pierre Fabre Laboratories reported that the European Medicines Agency (EMA) validated the submission for BRAFTOVI (encorafenib) + MEKTOVI (binimetinib) for the treatment of adult patients with BRAFV600-mutant advanced non-small cell lung cancer (NSCLC), who are either treatment naïve or have received prior therapy (Press release, Pierre Fabre, NOV 2, 2023, View Source [SID1234636833]).

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The submission is based on the results from the registrational PHAROS study,[1] which by independent review, showed an objective response rate (ORR) of 75% in treatment-naïve patients, with 59% maintaining a response for at least 12 months, and 46% in previously treated patients.[1]

"Lung cancer is the number one cause of cancer death worldwide,[2] and there are currently limited effective targeted treatment options for patients with BRAFV600-mutant advanced NSCLC. With our strategic focus on lung cancer and oncology precision medicine, this submission is the next step in delivering clinically meaningful change to oncology patient populations with high unmet needs," said Eric Ducournau, Chief Executive Officer of Pierre Fabre Laboratories.

The Phase 2 PHAROS trial[1] showed that one 450mg daily dose of BRAFTOVI and two 45mg daily doses of MEKTOVI[1] provided a meaningful clinical benefit for these patients with an ORR of 75% (95% CI: 62, 85) in treatment-naïve patients (n=59), with 59% of them maintaining a response for at least 12 months. For those patients who had received prior therapy (n=39), the ORR was 46% (95% CI: 30, 63), with 33% maintaining a response for at least 12 months. Median progression-free survival (PFS) was not reached at data cut-off for the treatment-naïve group (95% CI: 15.7, NE) and 9.3 months (95% CI: 6.2, NE) for the previously treated group. Median overall survival (OS) was not reached for either subgroup at the time of data cut-off. The most common treatment-related adverse events observed in the PHAROS trial were nausea (50%), diarrhoea (43%), fatigue (32%) and vomiting (29%).

These findings were simultaneously published in the Journal of Clinical Oncology and presented during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) congress on 4 June 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 who have received prior systemic therapy.[3]

About PHAROS

PHAROS (NCT03915951) is an ongoing, open-label, multicentre, non-randomised Phase 2 study to determine the efficacy and safety of BRAFTOVI + MEKTOVI in 98 patients with BRAFV600E-mutant metastatic NSCLC. Mutations were identified using next-generation sequencing or polymerase chain reaction tests performed at the patient’s local laboratory. The primary endpoint is confirmed ORR per RECIST v1.1, by independent radiology review (IRR); secondary objectives comprise additional efficacy endpoints including DoR, PFS, and OS as well as safety. The trial is being conducted across 56 sites in: Italy, the Netherlands, South Korea, Spain, and the U.S.

The PHAROS trial is sponsored by Pfizer Inc. and conducted with support from Pierre Fabre Laboratories.

About BRAF-mutant advanced 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 globally.[2] NSCLC accounts for approximately 80-85% of all lung cancers.[5]

Certain lung cancers are driven by acquired genetic abnormalities like a BRAF mutation. By using biomarkers to identify a person’s particular tumour type, treatment can become more personalised and effective, since the molecular makeup of a person’s cancer often determines how they respond to different therapies.

BRAF mutations occur in approximately 3-5% of NSCLC cases.[1] It stimulates tumour cell growth and proliferation by altering the MAP kinase (MAPK) signalling pathway. Targeting components of this pathway could potentially inhibit unchecked tumour 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 using biomarker tests.[7],[8] Advances in targeted therapy and more widespread use of biomarker testing have been associated with significant improvements in population-level NSCLC mortality in recent years.[9]

About BRAFTOVI + MEKTOVI

BRAFTOVI (encorafenib) is an oral small molecule BRAF kinase inhibitor and MEKTOVI (binimetinib) is an oral molecule MEK inhibitor, both of which target key proteins in the MAPK signalling pathway (RAS-RAF-MEK-ERK). Uncontrolled activation of this pathway has been shown to occur in many cancers, 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 results from the randomised, active-controlled, open-label, multicentre Phase 3 COLUMBUS trial.

In 2020, BRAFTOVI was EC-approved, in combination with cetuximab, for the treatment of adults with metastatic CRC with a BRAFV600E mutation. The approval was based on results from the randomised, active-controlled, open-label, multicentre Phase 3 BEACON CRC trial.

Pfizer has exclusive rights to commercialise BRAFTOVI and MEKTOVI in the U.S., Canada, and all countries in the Latin American, African, and Middle Eastern regions. Ono Pharmaceutical Co., Ltd. has exclusive rights to commercialise both products in Japan and South Korea, Medison has exclusive rights in Israel, and Pierre Fabre Laboratories has exclusive rights in all other countries, including Europe and Asia-Pacific.

The full product and safety information for the use of BRAFTOVI and MEKTOVI are outlined in the Summary of Product Characteristics (SmPC), published in the European public assessment report (EPAR) and available in all official EU languages. The full SmPC can be accessed at: View Source