Press Release Details
Array BioPharma Announces a 62% Observed Overall Survival 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 20th World Congress on Gastrointestinal Cancer
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
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 a mOS of 9.3 months, mPFS of 4.2 months and an ORR of 24%. The data cutoff for that analysis was
Enrollment in the randomized portion of the BEACON CRC trial is ongoing. Patients interested in participating in this trial may talk to their doctor to have their tumor tested for the BRAF mutation for eligibility to enroll in this new and important trial. Further details on the trial are available at clinicaltrials.gov (NCT02928224).
A PDF of the
Array will host an encore webcast presentation of the BEACON CRC safety lead-in data.
Encore Investor Webcast:
Axel Grothey, M.D., Division of Hematology/Oncology, Mayo Clinic
Saturday, June 23
4:30 pm CET (10:30 am ET)
Webcast, including replay and conference call slides:https://edge.media-server.com/m6/p/bn2j2g45
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.  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.  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 BRAFV600E mutation is more than two times higher than for those with wild-type BRAF.  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 (
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 BRAFV600E 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
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.
Encorafenib and binimetinib are investigational medicines and are not currently approved in any country.
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Array BioPharma Forward-Looking Statement
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements about the future development plans of encorafenib and binimetinib; expectations regarding approval of encorafenib and binimetinib for BRAF-mutant melanoma and timing of such approvals; expectations that events will occur that will result in greater value for Array; and the potential for the results of current and future clinical trials to support regulatory approval or the marketing success of encorafenib and binimetinib. Specifically, there is no assurance that results from the BEACON CRC and COLUMBUS trials will satisfy the requirements of regulatory authorities necessary for approval. These statements involve significant risks and uncertainties, including those discussed in our most recent annual report filed on Form 10-K, in our quarterly reports filed on Form 10-Q, and in other reports filed by Array with the
Senior Director, Investor Relations & Corporate Communications
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