Business Wire

Pierre Fabre & Array BioPharma Announce a 62% Observed OS at One Year from the Phase 3 BEACON CRC Safety Lead-In of the Combination of Encorafenib, Binimetinib and Cetuximab in BRAF-Mutant CRC at the ESMO GI Congress

Jaa

Not intended for UK- and US-based media

Pierre Fabre and its partner Array BioPharma Inc. today announced updated safety and efficacy results, including OS, from the safety lead-in of the Phase 3 BEACON CRC trial evaluating the triplet combination of encorafenib, a BRAF inhibitor, binimetinib, a MEK inhibitor and cetuximab, an anti-EGFR antibody, in patients with BRAF V600E -mutant metastatic colorectal cancer (CRC). The results showed that, at the time of analysis, the OS data were fully mature through 12.6 months and that the median OS had not yet been reached. The one-year overall survival rate for this cohort was 62%. These data were presented in an oral presentation on Saturday, June 23, at the ESMO 20th World Congress on Gastrointestinal Cancer in Barcelona, Spain.

The median progression-free survival (mPFS) for patients treated with the triplet was 8 months [95% CI 5.6-9.3] and is similar between patients receiving one prior line of therapy and patients receiving two prior lines of therapy. The confirmed overall response rate (ORR) was 48% and among the 17 patients who received only one prior line of therapy the ORR was 62%.

“The results of the BEACON CRC safety lead-in demonstrate substantial improvements in efficacy outcomes when compared to current approved standard of care benchmarks in patients with BRAF-mutant metastatic CRC. The median progression-free survival of 8 months is a meaningful improvement compared to the benchmark of about 2 months, and the overall survival of 62% at 12 months is very promising given that with current approved standards of care, half of patients will succumb to their disease within 4 to 6 months,” said Axel Grothey, M.D., Division of Hematology/Oncology, Mayo Clinic. “These data underscore the potential of this triplet combination to benefit patients with BRAF V600E -mutant metastatic CRC, who, despite their poor prognosis, currently have limited effective treatment options.”

The triple combination was generally well-tolerated with no unexpected toxicities. The most common grade 3 or 4 adverse events seen in at least 10% of patients were fatigue (13%), anemia (10%), increased blood creatine kinase (10%) and increased aspartate aminotransferase (10%).

The presentation also referenced updated, mature Phase 2 results for the doublet of encorafenib and cetuximab that showed an mOS of 9.3 months, mPFS of 4.2 months and an ORR of 24%. The data cutoff for that analysis was January 2018 with the last patient enrolled in April of 2015; a detailed presentation of these data will occur at a future medical congress.

About Colorectal Cancer

Worldwide, colorectal cancer is the third most common type of cancer in men and the second most common in women, with approximately 1.4 million new diagnoses in 2012. Globally in 2012, approximately 694,000 deaths were attributed to colorectal cancer.1 In the U.S. alone, an estimated 140,250 patients will be diagnosed with cancer of the colon or rectum in 2018, and approximately 50,000 are estimated to die of their disease.2 In the U.S., BRAF mutations are estimated to occur in 10% to 15% of patients with colorectal cancer and represent a poor prognosis for these patients.3-6 The risk of mortality in CRC patients with the BRAF V600E mutation is more than two times higher than for those with wild-type BRAF.7 Several approved standard of care benchmarks for patients with BRAF-mutant CRC whose disease has progressed after one or two prior lines of therapy, range between 4% to 8% ORR, 1.8 and 2.5 months mPFS and 4 and 6 months mOS.8–14 Recently published results (April 2018; June 2017) from BRAF-containing triplet regimens in this population resulted in an mOS of approximately 9 months. Specifically, the triplet combination of dabrafenib, a BRAF inhibitor, trametinib, a MEK inhibitor and panitumumab, a monoclonal EGFR antibody, demonstrated an mOS of 9.1 months (n=91) and the triplet combination of vemurafenib, a BRAF inhibitor, cetuximab and irinotecan, a chemotherapy, demonstrated an mOS of 9.6 months (n=49).8,15 Based on recent prospective historical data, the prevalence of microsatellite instability-high (MSI-H) in tumours from patients with metastatic BRAF-mutant CRC ranged from 14% in a recent Phase 1b/2 trial (NCT01719380) (Pierre Fabre, data on file) to 18% in a recent Southwestern Oncology Group (SWOG) randomized phase 2 trial.8

About BEACON CRC

BEACON CRC is a randomized, open-label, global trial evaluating the efficacy and safety of encorafenib, binimetinib and cetuximab in patients with BRAF-mutant metastatic CRC whose disease has progressed after one or two prior regimens. BEACON CRC is the first and only Phase 3 trial designed to test a BRAF/MEK combo targeted therapy in BRAF-mutant advanced CRC. Thirty patients were treated in the safety lead-in and received the triplet combination (encorafenib 300 mg daily, binimetinib 45 mg twice daily and cetuximab per label). Of the 30 patients, 29 had a BRAF V600E mutation. MSI-H, resulting from defective DNA mismatch repair, was detected in only 1 patient. As previously announced, the triplet combination demonstrated good tolerability, supporting initiation of the randomized portion of the trial.

The randomized portion of the BEACON CRC trial is designed to assess the efficacy of encorafenib in combination with cetuximab with or without binimetinib compared to cetuximab and irinotecan-based therapy. Approximately 615 patients are expected to be randomized 1:1:1 to receive triplet combination, doublet combination (encorafenib and cetuximab) or the control arm (irinotecan-based therapy and cetuximab). The primary endpoint of the trial is overall survival of the triplet combination compared to the control arm. Secondary endpoints address efficacy of the doublet combination compared to the control arm, and the triplet combination compared to the doublet therapy. Other secondary endpoints include PFS, ORR, duration of response, safety and tolerability. Health related quality of life data will also be assessed. The trial is being conducted at over 200 investigational sites in North America, South America, Europe and the Asia Pacific region. Patient enrollment is expected to be completed in 2018.

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 BEACON CRC trial and the Phase 3 COLUMBUS trial.

The U.S. Food and Drug Administration (FDA) is currently reviewing the New Drug Applications (NDAs) to support use of the combination of encorafenib and binimetinib for the treatment of patients with BRAF V600E or BRAF V600K -mutant, unresectable or metastatic melanoma. The FDA set a target action date under the Prescription Drug User Fee Act (PDUFA) of June 30, 2018 for both applications. The European Medicines Agency (EMA), as well as the Swiss Medicines Agency (Swissmedic) and the Australian Therapeutic Goods Administration (TGA), are reviewing the Marketing Authorization Applications (MAAs) submitted by Pierre Fabre and Japan's Pharmaceuticals and Medical Devices Agency (PMDA) has accepted the Manufacturing and Marketing Approval (MMA) applications submitted by Ono Pharmaceutical Co, Ltd.

Encorafenib and binimetinib are investigational medicines and are not currently approved in any country.

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] Global Cancer Facts & Figures 3rd Edition. American Cancer Society. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/global-cancer-facts-and-figures/global-cancer-facts-and-figures-3rd-edition.pdf. Accessed June 2018.

[2] Cancer Facts & Figures 2018. American Cancer Society. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf. Accessed June 2018.

[3] Saridaki et al., PLoS One. 2013

[4] Loupakis et al., Br J Cancer. 2009

[5] Sorbye H, et al. PLoS One. 2015

[6] Vecchione, et al. Cell. 2016

[7] Safaee Ardekani G, Jafarnejad SM, Tan L, et al. The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis. PLoS One. 2012;7(10):e47054.

[8] Kopetz et al., ASCO 2017

[9] De Roock et al., Lancet Oncol, 2010

[10] Ulivi et al., J Transl Med. 2012

[11] Peeters et al., ASCO 2014

[12] Saridaki et al., PLoS One. 2013

[13] Loupakis et al., Br J Cancer. 2009

[14] Seymour et al., Lancet Oncol, 2013 (supplementary appendix)

[15] Corcoran et al., Cancer Discovery, 2018

Contact information

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

Tietoja julkaisijasta

For more than 50 years, Business Wire has been the global leader in press release distribution and regulatory disclosure.

Tilaa tiedotteet sähköpostiisi

Haluatko tietää asioista ensimmäisten joukossa? Kun tilaat mediatiedotteemme, saat ne sähköpostiisi välittömästi julkaisuhetkellä. Tilauksen voit halutessasi perua milloin tahansa.

Lue lisää julkaisijalta Business Wire

Kalray Releases the Kalray Neural Network 3.0 (KaNN) to Accelerate Artificial Intelligence Application Development13.11.2018 21:26Tiedote

Kalray (Euronext Growth Paris – ALKAL), a pioneer in processors for new intelligent systems, today announced the launch of the Kalray Neural Network 3.0 (KaNN), a platform for Artificial Intelligence application development. KaNN allows developers to seamlessly port their AI-based algorithms from well-known machine learning frameworks including Caffe®, Torch® and TensorFlow® onto Kalray’s Massively Parallel Processor Array (MPPA®) intelligent processor. Artificial Intelligence is at the heart of a growing number of applications such as autonomous vehicles, intelligent storage servers, data centers, robotics, drones, and more. Kalray’s manycore MPPA® intelligent processor has been architected from the ground up to meet the incredible performance requirements of such advanced applications. However, it is crucial to provide an easy way for AI developers to seamlessly support the AI networks they develop. “The Kalray MPPA® intelligent processor is capable of processing massive amounts of d

Sharjah International Book Fair 2018 Celebrates Reading and Culture with 2.23 Million Visitors13.11.2018 21:17Tiedote

The world’s third largest celebration of the written word, the Sharjah International Book Fair (SIBF), has put up yet another record performance in its 37th annual edition. Themed ‘A Tale of Letters’, the event was a dream come true occasion for book lovers, who had access to 20 million books, all under one roof. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20181113006044/en/ Sharjah International Book Fair 2018 - Provided by Sharjah Book Authority (Photo: Business Wire) Organised by the Sharjah Book Authority (SBA) in the emirate of Sharjah, cultural capital of the United Arab Emirates (UAE), SIBF 2018 witnessed a footfall of 2.23 million visitors in 11 days, including 230,000 school students who poured in from around the country. The Sharjah International Book Fair hosted 1,874 publishers from 77 countries who brought in 1.6 million titles, 80,000 of which were seen at the fair for the first time. It also offered its stage

Communications and Business Transformation Strategist Brian Ellner Joins BCW to Lead U.S. Corporate Practice13.11.2018 21:00Tiedote

BCW (Burson Cohn & Wolfe), a leading global communications agency, announced today that Brian Ellner has joined as Executive Vice President, Global Corporate Solutions, responsible for leading and growing BCW’s U.S. Corporate Practice. Ellner takes on the role previously held by Aranthan “AJ” Jones II, who will now lead the firm’s Public Affairs and Crisis Practice in the U.S. “Corporations are navigating an increasingly complex world where their reputations are tied not only to their own performance but also to their behavior on topics like climate, gender pay equity, visa status, diversity and inclusion and the environment,” said Chris Foster, President, North America, BCW. “Brian has deep experience helping clients build and protect their reputations, manage business transformation and create authentic social purpose engagements. He is a seasoned strategic counselor and power player in the New York business world and will bring our clients and our business clear opportunities for gr

Alliance Ventures Invests in Enevate to Advance Li-ion Battery Technology for Electric Vehicles13.11.2018 19:00Tiedote

Alliance Ventures, the strategic venture capital arm of Renault-Nissan-Mitsubishi, has announced today that it has invested in the latest round of funding in Enevate Corporation, an advanced lithium-ion (Li-ion) battery technology company based in Irvine, California. This marks the latest technology investment by Alliance Ventures, launched earlier this year to support start-ups, early-stage development, and entrepreneurs at the cutting edge of next-generation systems for the automotive industry. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20181113005136/en/ Francois Dossa, Alliance Global Vice President, Ventures and Open Innovation, said: “We are pleased to participate in Enevate’s latest funding round. This strategic investment allows us to support the development of Enevate’s proprietary, cutting-edge electrode technology. Continued development in this critical field will help us accelerate the electrification of our ve

P&G Tackles Clean Water, Gender Equality and Plastic Waste in 2018 CSR Report13.11.2018 17:05Tiedote

The Procter & Gamble Company (NYSE:PG) extends its long history of doing good in the world by bringing the comforts of home to those impacted by disasters, continuing to spark conversations about diversity, inclusion and gender equality with its advertising and making meaningful impact on the environment with new 2030 goals including a vision to ensure that none of the Company’s packaging ends up in the world’s oceans. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20181113005694/en/ P&G issued its 2018 Citizenship Report, which highlights the Company's progress in its Citizenship priority areas of Community Impact, Diversity & Inclusion, Gender Equality and Environmental Sustainability, all of which are based in a foundation of Ethics and Corporate Responsibility. (Graphic: Business Wire) Captured in the 2018 Citizenship Report released today, P&G highlights the recent activities that define the Company as a force for good an

ISACA Refreshes COBIT Framework to Address Latest Business Technology Trends and Standards13.11.2018 17:03Tiedote

ISACA, the global association for information and technology (I&T) audit, risk, governance and security professionals, has released its first update to the COBIT framework in nearly seven years. The new version, COBIT® 2019, provides comprehensive and more practical guidance to help enterprises better govern and manage their information and technology. The COBIT framework is used by enterprises in all industries around the globe, and COBIT publications have been downloaded more than one million times. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20181113005757/en/ ISACA introduced COBIT in 1996 to provide and organize a set of controls for IT. The new iteration of COBIT will come in four phases and will include focus areas reflecting trends and priorities in technology (e.g., DevOps, cybersecurity), updates aligned with the latest industry standards, and a design guide that provides flexibility and guidance to help organizat

Uutishuoneessa voit lukea tiedotteitamme ja muuta julkaisemaamme materiaalia. Löydät sieltä niin yhteyshenkilöidemme tiedot kuin vapaasti julkaistavissa olevia kuvia ja videoita. Uutishuoneessa voit nähdä myös sosiaalisen median sisältöjä. Kaikki STT Infossa julkaistu materiaali on vapaasti median käytettävissä.

Tutustu uutishuoneeseemme