Pierre Fabre and Its Partner Array BioPharma Announce Additional Median Overall Survival Results of Encorafenib and Binimetinib in Patients with Braf-Mutant Advanced Melanoma
Pierre Fabre and its partner Array BioPharma Inc. today announced updated results from the Phase 3 COLUMBUS trial in BRAF-mutant advanced melanoma. The results showed median overall survival (mOS) was 33.6 months for patients treated with the combination of encorafenib and binimetinib compared with 16.9 months for patients treated with vemurafenib as a monotherapy. The combination reduced the risk of death compared with vemurafenib monotherapy (hazard ratio [HR] of 0.61 [95% CI: 0.47–0.79], p<0.0001]. The observed efficacy of vemurafenib in the control arm is also consistent with historical data, providing an additional benchmark for validating the patient population and results observed in COLUMBUS.1,2 Further, the two-year OS with the combination therapy was 58%. These results will be part of an oral presentation today at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Illinois, and have been selected for the “Best of ASCO” program.
Importantly, the presentation included data showing limited use of post-trial immunotherapy, which is consistent with other published pivotal trials of BRAF and MEK inhibitors in BRAF-mutant advanced melanoma.1,3
“These data indicate that regardless of treatment group, the use of subsequent immunotherapies was similar, and therefore indicate that post-trial treatments are unlikely to have contributed to the OS results we’ve seen,” said Professor Reinhard Dummer, University of Zurich, lead author and Vice-Chairman of the Department of Dermatology in the University Hospital of Zürich, Switzerland. “We’re pleased to present this data at ASCO which builds upon previous analyses of the COLUMBUS data and further support our belief that encorafenib and binimetinib could be a promising new treatment option for patients with BRAF-mutant advanced melanoma.”
Additionally, the updated median progression-free survival (mPFS) results for patients treated with the combination of encorafenib and binimetinib remained consistent with what was previously reported: 14.9 months versus 7.3 months for patients treated with vemurafenib (HR=0.51 [95% CI 0.39–0.67]; p<0.0001).
As previously reported, the combination of encorafenib and binimetinib was generally well-tolerated. Grade 3–4 adverse events (AEs) that occurred in more than 5% of patients receiving the combination were increased gamma-glutamyltransferase (GGT; 9%), increased blood creatine phosphokinase (CK; 7%) and hypertension (6%). The incidence of selected any grade AEs of special interest, defined based on toxicities commonly associated with commercially available BRAF+MEK inhibitor treatments, for patients receiving the combination of encorafenib and binimetinib included: rash (22%), serous retinopathy including retinal pigment epithelial detachment (20%), pyrexia (18%) and photosensitivity (5%). Full safety results of COLOMBUS Part 1 were published in The Lancet Oncology.
Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates.4,5 There are about 200,000 new cases of melanoma diagnosed worldwide each year, approximately half of which have BRAF mutations, a key target in the treatment of metastatic melanoma.4,6,7,8
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 with 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 twice daily as a monotherapy. 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 published in The Lancet Oncology earlier this year (online March 2018, print May 2018), 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<0.0001). 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.
 Ascierto PA, et al. Lancet Oncol. 2016;17:1248-1260.
 Robert C, et al. Eur J Cancer. 2015;51:S663-S664.
 Long GV, et al. Ann Oncol. 2017;28:1631-1639.
 Melanoma Skin Cancer. American Cancer Society. Available at: https://www.cancer.org/cancer/melanoma-skin-cancer.html. Accessed May 2018.
 A Snapshot of Melanoma. National Cancer Institute. Available at: https://seer.cancer.gov/statfacts/html/melan.html. Accessed May 2018.
 Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed May 2018.
 Klein O, et al. Eur J Cancer, 2013.
 American Cancer Society. What Causes Melanoma Skin Cancer? 2016. https://www.cancer.org/cancer/melanoma-skin-cancer/causes-risks-prevention/what-causes.html. Accessed May, 2018.
Valérie Roucoules, (33) 1 49 10 83 84
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 jo ennen kuin ne uutisoidaan? Kun tilaat tiedotteemme, saat ne sähköpostiisi yhtä aikaa suomalaisen median kanssa. Tilauksen voit halutessasi perua milloin tahansa.
Lue lisää julkaisijalta Business Wire
Octapharma announces approval of new Nuwiq® product strengths in Europe, increasing dosing flexibility for patients with haemophilia A18.6.2018 10:06 | Tiedote
Octapharma announced today that the European Medicines Agency (EMA) has approved an extension of marketing authorisation for its human cell line-derived recombinant factor VIII (rFVIII) product, Nuwiq®. New single dose vial strengths of 2500, 3000 and 4000 International Units (IU) will be available in Europe, in addition to the current strengths of 250, 500, 1000 and 2000 IU. The new Nuwiq® vial strengths have been available in the US since September last year, following approval by the FDA. Nuwiq® is indicated in adults and children of all ages for on-demand treatment and prophylaxis, including during surgery, to prevent and control bleeding episodes in patients with haemophilia A. This expanded array of vial strengths has the potential to increase treatment options for patients with haemophilia A by improving dosing flexibility. Patients who previously required more than one vial per infusion may be able to reduce the number of vials needed. Nuwiq® is the only rFVIII available in an
STATS and SpokeHub Partner to Power Deeper, More Meaningful Conversations Around the 2018 FIFA World Cup18.6.2018 10:00 | Tiedote
Today, STATS, the worldwide leader in sports data and intelligence, and SpokeHub announced a new partnership to bring STATS Insights to SpokeHub’s social engagement platform, connecting worldwide World Cup football (soccer) fans with content that is more impactful. Download the app today to see the match scores, player insights, and engage with World Cup fans everywhere! STATS Insights leverages more than 37 years of research experience to deliver deep historical and comparative statistical insights, play-by-play descriptions and in-game trends based on events as they happen in the match. Before, during and after each match, SpokeHub will harness STATS Insights to amplify conversations among World Cup football communities. During the game, live Insights will deliver trends on players and teams based on in-game events, statistics and milestones. “No sporting event gets global attention like the World Cup, and every fan is looking for deeper analysis around their favorite teams and playe
Celltrion Completes Resubmission to FDA for Proposed Trastuzumab Biosimilar18.6.2018 05:53 | Tiedote
Celltrion (KRX:068270) has made a resubmission to the FDA (U.S. Food and Drug Administration) to obtain its marketing approval for CT-P6, a proposed mAb biosimilar to Herceptin® (trastuzumab). Celltrion submitted its abbreviated Biologics License Applications (aBLAs) for CT-P10 and CT-P6 to the FDA in April and May of last year, respectively. However, it received CRLs (complete response letters) from the FDA related to the warning letter issued by the FDA in January 2018, related to the manufacturing facility in Incheon, South Korea. Celltrion had completed the resubmission for the approval of CT-P10, a proposed biosimilar to Rituxan® (rituximab) last month. In accordance with FDA regulations, the approval procedure will be usually finalized within six months from the resubmission, so Celltrion expects the approval for the U.S. market of the two proposed biosimilars within this calendar year. FDA has notified Celltrion of its re-inspection schedule regarding regular audit results, and
CES Asia: Innovation at the Speed of 5G15.6.2018 17:59 | Tiedote
CES Asia® 2018 wrapped today with the rapid pace of global innovation front and center over the show’s three day duration. The next stage of technology advancements were showcased across vehicle tech, robotics, artificial intelligence (AI), virtual and augmented reality, digital health and more. The event, 24 percent larger than last year in terms of footprint, cemented itself as the place to fully experience how the pace of technology is accelerating globally. CES Asia, the premier event for tech innovation in the Asian marketplace, will return to Shanghai, China, June 11-13, 2019. “5G and AI are igniting growth across the entire tech ecosystem changing the way we interact with technology and the world around us,” said Gary Shapiro, president and CEO, Consumer Technology Association (CTA)™. “It’s incredible to see technology refining and reinventing itself at such a fast pace. Just six months ago we were at CES with life-altering tech all around us. This week, I saw that technology re
bluebird bio Presents New Data from Northstar (HGB-204) and Northstar-2 (HGB-207) Studies of LentiGlobin™ Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia at Annual Congress of the European Hematology Association15.6.2018 13:00 | Tiedote
bluebird bio, Inc. (Nasdaq: BLUE) announced that new data from the completed Phase 1/2 Northstar (HGB-204) study in adolescents and adults with transfusion-dependent β-thalassemia (TDT) and any genotype, and its ongoing, Phase 3 Northstar-2 (HGB-207) multicenter clinical study of LentiGlobin™ investigational gene therapy in patients with TDT and non-β0/β0 genotypes, will be presented in an oral session on June 16 at the 23rd Annual Congress of the European Hematology Association by Franco Locatelli, M.D., Ph.D., of the IRCCS Ospedale Pediatrico Bambino Gesù of Rome, Italy. “The maturing data from HGB-204 and HGB-207 suggest that one-time treatment with LentiGlobin may address the underlying genetic cause of TDT. With our refined manufacturing process, the majority of patients with TDT and non-β0/β0 genotypes are transfusion-free and producing total hemoglobin at normal or near-normal levels,” said David Davidson, M.D., chief medical officer, bluebird bio. “We are on track to submit a m
bluebird bio Announces New Interim Data from Phase 1 (HGB-206) Study of LentiGlobin™ Gene Therapy in Patients with Severe Sickle Cell Disease at Annual Congress of the European Hematology Association15.6.2018 13:00 | Tiedote
bluebird bio, Inc. (Nasdaq: BLUE) today announced new interim data from the ongoing HGB-206 Phase 1 multicenter clinical study of LentiGlobin investigational gene therapy in patients with severe sickle cell disease (SCD) will be presented in an oral presentation on Saturday, June 16 at the 23rd Congress of the European Hematology Association (EHA) by Julie Kanter, M.D., Medical University of South Carolina, Charleston, South Carolina. “The consistent production of increased amounts of anti-sickling HbAT87Q in the Group C patients reflects the substantial positive impact of the changes introduced with the amended HGB-206 study protocol and refined manufacturing process. All four Group C patients with greater than or equal to three months follow-up are making over 30 percent anti-sickling HbAT87Q. The first patient treated, now with six months of follow-up, is producing over 60 percent anti-sickling HbAT87Q with a normal total hemoglobin level of 14.2 g/dL,” said David Davidson, M.D., ch
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