Pierre Fabre and Array BioPharma Announce COLUMBUS Phase 3 Study Overall Survival Results in BRAF-Mutant Melanoma Will Be Presented at 2018 ASCO Annual Meeting

Pierre Fabre with its partner Array BioPharma will be presenting data from the pivotal Phase 3 COLUMBUS trial in patients with BRAF-mutant melanoma on June 4

CASTRES, France--(BUSINESS WIRE)--Pierre Fabre with its partner Array BioPharma Inc. will present overall survival (OS) data from its late-stage candidates encorafenib, a BRAF inhibitor, and binimetinib, a MEK inhibitor, at the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO), being held June 1-5, 2018 in Chicago, Illinois.

Survival data from the Phase 3 COLUMBUS trial of encorafenib and binimetinib in BRAF-mutant unresectable advanced melanoma will be highlighted in an oral presentation on June 4, 2018.

“We are delighted by the continued promising results of the encorafenib and binimetinib combination observed in the COLUMBUS trial,” said Frédéric Duchesne, Chief Executive Officer of the Pierre Fabre Pharmaceuticals Division. “As treatment options for patients with -mutant melanoma are limited, there remains a need for new options that can demonstrate efficacy and tolerability. We look forward to sharing additional information about our exciting combination targeted therapy with the medical community at this year’s ASCO.

Oral Presentation:

The abstract is available on the ASCO website.

About Melanoma

Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates. [1, 2] There are about 200,000 new cases of melanoma diagnosed worldwide each year, approximately half of which have BRAFmutations, a key target in the treatment of metastatic melanoma. [1, 3, 4]

About COLUMBUS
The COLUMBUS trial, (NCT01909453), is a two-part, international, randomized, open-label Phase 3 trial evaluating the efficacy and safety of the combination of encorafenib and binimetinib compared to vemurafenib and encorafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic melanoma with BRAF^V600 mutation. Prior immunotherapy treatment was allowed. Over 200 sites across North America, Europe, South America, Africa, Asia and Australia participated in the trial. Patients were randomized into two parts:

• In Part 1, 577 patients were randomized 1:1:1 to receive encorafenib 450 mg daily + binimetinib 45 mg twice daily (COMBO450), encorafenib, 300 mg daily (ENCO 300), or vemurafenib, 960 mg alone twice daily alone. The dose of encorafenib in the combination arm is 50% higher than the single-agent maximum tolerated dose of 300 mg. A higher dose of encorafenib was possible due to improved tolerability when combined with binimetinib. The primary endpoint for the COLUMBUS trial was a median progression-free survival (mPFS) comparison of the COMBO450 arm versus vemurafenib. mPFS is determined based on tumor assessment (RECIST version 1.1 criteria) by a Blinded Independent Central Review (BICR). Secondary endpoints include a comparison of the mPFS of COMBO450 arm to that of ENCO300 and a comparison of overall survival (OS) in patients treated in the COMBO450 arm to that of vemurafenib alone. Results from Part 1 of the COLUMBUS trial previously presented at the 2016 Society for Melanoma Research Annual Congress showed that COMBO450 more than doubled mPFS in patients with advanced BRAF-mutant melanoma, with a mPFS of 14.9 months compared with 7.3 months observed with vemurafenib (HR 0.54 [95% CI 0.41-0.71], p<0.001). In the secondary mPFS comparison of COMBO450 to ENCO300, ENCO300 demonstrated a mPFS of 9.6 months (HR 0.75 [95% CI 0.56-1.00), p=0.051).
• In Part 2, 344 patients were randomized 3:1 to receive encorafenib 300 mg daily plus binimetinib 45 mg twice daily (COMBO300) or ENCO300. Part 2 was designed to provide additional data to help evaluate the contribution of binimetinib to the combination of encorafenib and binimetinib.

As the secondary endpoint comparison of mPFS between the COMBO450 arm and ENCO300 arm in Part 1 did not achieve statistical significance, the protocol-specified analysis of OS is descriptive.

About Encorafenib and Binimetinib
BRAF and MEK are key protein kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Research has shown this pathway regulates several key cellular activities, including proliferation, differentiation, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, including melanoma and colorectal cancer. Encorafenib is a late-stage small molecule BRAF inhibitor and binimetinib is a late-stage small molecule MEK inhibitor, both of which target key enzymes in this pathway. Encorafenib and binimetinib are being studied in clinical trials in advanced cancer patients, including the Phase 3 COLUMBUS trial and the Phase 3 BEACON CRC trial.

Pierre Fabre has exclusive rights to commercialize encorafenib and binimetinib in Europe, Asia, Latin America and Australia. Pierre Fabre’s development partner, Array BioPharma, has exclusive rights in the U.S. and Canada, and has granted Ono Pharmaceutical exclusive rights to commercialize both products in Japan and South Korea. Encorafenib and binimetinib are investigational medicines and are not currently approved in any country.

References
[1] Melanoma Skin Cancer. American Cancer Society. Available at: https://www.cancer.org/cancer/melanoma-skin-cancer.html. Accessed May 2018.
[2] A Snapshot of Melanoma. National Cancer Institute. Available at: https://seer.cancer.gov/statfacts/html/melan.html. Accessed May 2018.
[3] Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed May 2018.
[4] Klein O, et al. Eur J Cancer, 2013.

Contacts

Pierre Fabre
Valérie Roucoules, (33) 1 49 10 83 84
valerie.roucoules@pierre-fabre.com