Pierre Fabre and EORTC open a large Phase III clinical study in the adjuvant setting of stage IIB-C melanoma

First study conducted in the adjuvant setting with a combination of BRAF and MEK inhibitors in high-risk stage II BRAF V600E/K-mutant cutaneous melanoma

A global partnership between EORTC and Pierre Fabre to advance research in melanoma

CASTRES,France and BRUSSELS,May 24,2022 -- Pierre Fabre and the European Organisation for Research and Treatment of Cancer (EORTC) today announced the screening of the first patient with a resected stage II BRAF-mutant melanoma for the phase III study COLUMBUS-AD (NCT05270044; EORTC-2139-MG).

COLUMBUS-AD is a pioneering study to evaluate whether the combination of BRAF and MEK inhibitors encorafenib (Braftovi®) and binimetinib (Mektovi®) can prolong recurrence-free survival (RFS) and improve distant metastasis-free survival (DMFS) and overall survival (OS) as compared to placebo in participants with surgically resected stage IIB-C BRAF V600E/K-mutant cutaneous melanoma.

"Pierre Fabre's partnership with EORTC is now accelerating with the opening of COLUMBUS-AD",said Dr Deborah Szafir,Executive Vice President,Head of Medical and Patient Consumer Division at Pierre Fabre. "Building on the clinical benefits that our medicines have demonstrated in advanced disease,we are eager for patients with a BRAF-mutated tumour to explore the adjuvant setting in an earlier stage of the disease as the unmet medical need remains high."

Approximately 815 patients will be enrolled in COLUMBUS-AD. More than 160 sites in up to 25 countries worldwide will participate in the study.

Despite the remarkable progress made in the treatment of advanced melanoma activating the BRAF mutation,unfortunately there remains a high unmet need in earlier stages of the disease. It is estimated that 18% of stage IIB and 25% of stage IIC patients die from melanoma within 10 years from diagnosis.

"The screening of patients for COLUMBUS-AD focuses on patients with surgically resected high-risk IIB-C BRAF V600E/K-mutant cutaneous melanoma",said study coordinator assoc. prof. Dr. Alexander C.J. Van Akkooi,MD PhD,from the Melanoma Institute Australia (MIA) and past chairman of the EORTC Melanoma Group. "It is essential to test the tumouras early as possible for BRAF mutation,so that eligible patients can get a chance to participate into COLUMBUS-AD".

Patients included in the study must have undergone resection of a stage IIB-C melanoma with a BRAF V600E/K mutation,confirmed on resected tumour sample by a central laboratory,and a negative result on sentinel node biopsy. Patients must also have fully recovered from the surgery,have a good performance status (ECOG 0/1),and adequate hematologic,hepatic,cardiac,coagulation and renal functions.

Patients will receive encorafenib and binimetinib or placebo for up to 12 months. They will be followed-up monthly during the treatment period,then every 3 months up to year 3,and then at regular intervals. The participants will be followed-up for 10 years in total.

Pierre Fabre has a long-standing commitment to the melanoma community and takes a unique holisticapproach to skin health with expertise in oncology,dermatology and dermo-cosmetics. EORTC,a unique academic clinical research organisation uniting clinical cancer research experts across the globe,shares Pierre Fabre's commitment to improving the standard of cancer treatment for patients.

About Melanoma

Melanoma develops when unrepaired DNA damage to skin cells triggers mutations that may lead them to multiply and form malignant tumours.1 There are about 324,000 new cases of melanoma diagnosed worldwide each year,approximately half of which have BRAF mutations,a key target in the treatment of metastatic melanoma.2,3,4 By 2025,the number of cases is expected to increase to over 340,000.5

About the EORTC

The European Organisation for Research and Treatment of Cancer (EORTC) is a non-governmental,non-profit organisation,which unites clinical cancer research experts,throughout Europe,to define better treatments for cancer patients to prolong survival and improve quality of life. Spanning from translational to large,prospective,multi-centre,phase III clinical trials that evaluate new therapies and treatment strategies as well as patient quality of life,its activities are coordinated from EORTC Headquarters,a unique international clinical research infrastructure,based in Brussels,Belgium.

For further information,please visit the EORTC website: www.eortc.org

About encorafenib (Braftovi®) and binimetinib (Mektovi®)

Encorafenib is an oral small-molecule BRAF kinase inhibitor and binimetinib is an oral small-molecule MEK inhibitor that targets key enzymes in the MAPK signalling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of proteins in this pathway has been shown to occur in many cancers,including melanoma,colorectal cancer,non-small-cell lung cancer,thyroid and others.

Pierre Fabre has exclusive rights to develop and commercialise Braftovi® and Mektovi® worldwide,except in the US and Canada,where Pfizer (Array BioPharma) retains exclusive rights; Israel,where Medison has exclusive rights; Japan and South Korea,where Ono Pharmaceutical has exclusive rights to commercialise both products; and Latin America,Africa and Middle East where both products have been sub-licensed to Pfizer.

Pierre Fabre is the sponsor of the COLUMBUS-AD Phase III study. The overall development of Braftovi® and Mektovi® is driven in partnership with Pfizer in diverse indications.

About Pierre Fabre Oncology

The Pierre Fabre Group is the second largest private French healthcare group and the second largest dermo-cosmetics manufacturer in the world. In 2021,it generated €2.5 billion in revenues,66% of which came from international sales. Pierre Fabre employs some 9500 people worldwide and manufactures over 95% of its products in France. Its portfolio includes several medical franchises and international brands,including Pierre Fabre Oncology,Pierre Fabre Dermatology,Eau Thermale Avène,Klorane,Ducray,René Furterer,A-Derma and Pierre Fabre Oral Care.

In oncology,Pierre Fabre enjoys over 35 years of experience in discovery,development,manufacturing and marketing,with a portfolio of therapies covering colorectal,breast,lung cancers,melanoma and pre-cancerous conditions such as actinic keratosis. Pierre Fabre's innovation and commercialization efforts in oncology are focused on targeted therapies,biotherapies and immuno-oncology.

The Pierre Fabre Group is 86%-owned by the Pierre Fabre Foundation,a public-interest foundation,and secondarily by its own employees through an international employee stock ownership plan.

Further information about Pierre Fabre can be found at www.pierre-fabre.com,@PierreFabre.

References

[1] Neoplasma. 2016;63(4):510-7. doi: 10.4149/neo_2016_403.[2] American Cancer Society. What Causes Melanoma Skin Cancer. Available at: https://www.cancer.org/cancer/melanoma-skin-cancer/causes-risks-prevention/what-causes.html. Accessed May 2021.

[3] International Agency for Research on Cancer. Melanoma of skin. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/16-Melanoma-of-skin-fact-sheet.pdf. Accessed May 2021.

[4] Klein O,et al. Eur J Cancer 2013;49:1073–1079.

[5] Melanoma UK. 2020 Melanoma Skin Cancer Report. Available at: 2020 MELANOMA SKIN CANCER REPORT | Melanoma UK. Accessed May 2021.

Contacts:

EORTC

Pierre Fabre

Isabelle GAUTHEROT

Laure SGANDURRA

communication@eortc.org

laure.sgandurra@pierre-fabre.com