Array BioPharma Announces BRAFTOVI + MEKTOVI + Cetuximab Meet Primary Endpoints of ORR and OS in Phase 3 BEACON CRC Trial Interim Analysis for the Treatment of BRAF(V600E)-mutant Metastatic Colorectal Cancer
- BRAFTOVI combinations showed statistically significant improvement in ORR and OS versus control -
- BRAFTOVI + MEKTOVI + cetuximab reduced the risk of death by 48% versus control - - Potential to be the first chemotherapy-free, targeted regimen for metastatic CRC patients - - Array intends to submit these data for marketing approval in 2H19 - - Array will host a conference call today, Tuesday, May 21, 2019, at 9:00 am Eastern Time - BOULDER, Colo., May 21, 2019 /PRNewswire/ -- Array BioPharma Inc. (Nasdaq: ARRY) today announced positive results from the interim analysis of the Phase 3 BEACON CRC trial evaluating the combination of BRAFTOVI® (encorafenib), a BRAF inhibitor, MEKTOVI® (binimetinib), a MEK inhibitor, and ERBITUX® (cetuximab), an anti-EGFR antibody (BRAFTOVI Triplet), in patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC), following one or two prior lines of therapy. The trial met both primary endpoints of confirmed objective response rate (ORR), as assessed by Blinded Independent Central Review (BICR), and overall survival (OS). Array intends to submit these results of the BEACON CRC trial for marketing approval in the second half of 2019. Results from the trial showed that BRAF-mutant mCRC patients treated with the BRAFTOVI Triplet demonstrated a statistically significant improvement in ORR (26.1% vs. 1.9%, p<0.0001, per BICR) and OS (median 9.0 months vs. 5.4 months, [HR 0.52, 95% CI (0.39-0.70), p<0.0001]) compared to cetuximab plus irinotecan-containing regimens (Control). "The BEACON CRC trial is the first Phase 3 trial in patients with BRAFV600E-mutant mCRC and these results show a significant improvement compared to available standard of care options for this patient population," said Scott Kopetz, M.D., Ph.D., FACP, Associate Professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. "Given that there are no therapies currently FDA-approved for this patient population, I believe the results of the BEACON CRC trial will be practice-changing." The analysis of ORR was based on the first 331 randomized patients, while the interim analysis of OS included all 665 randomized patients, and was based on a data cutoff date in February of 2019, approximately two weeks after the last patient was enrolled. Future analyses will assess ORR on the total population and OS with longer follow up. Results from the secondary endpoint analysis showed that patients treated with the combination of BRAFTOVI and cetuximab (BRAFTOVI Doublet) demonstrated a statistically significant improvement in ORR (20.4% vs. 1.9%, p<0.0001, per BICR) and OS (median 8.4 months vs. 5.4 months, [HR 0.60, 95% CI (0.45-0.79), p=0.0003]) compared to Control. A descriptive comparison of the BRAFTOVI Triplet to the BRAFTOVI Doublet demonstrated a positive trend across endpoints including ORR and OS [HR 0.79, 95% CI (0.59-1.06), nominal p=0.1164]. In patients receiving one prior line of therapy, ORR as assessed by BICR was 34.3% with the BRAFTOVI Triplet and 22.4% with the BRAFTOVI Doublet, while at this time the OS for both arms is consistent with that seen in the overall population. "We are pleased to announce positive results from the BEACON CRC trial, including that the BRAFTOVI Triplet reduced the risk of death by 48% versus control," said Ron Squarer, CEO, Array BioPharma. "We are deeply grateful to the patients and investigators whose participation has helped bring us one step closer to delivering a new standard of care for patients with BRAF-mutant mCRC. This has the potential to be the first chemotherapy-free, targeted regimen for mCRC patients, a population with a very high unmet need for effective treatments." As demonstrated in the control arm of the BEACON CRC trial and consistent with historical data, patients with BRAF-mutant mCRC generally have a poor prognosis with currently available treatments and currently there are no FDA-approved therapies specifically indicated for this high unmet need population. [1-12,14] BRAF mutations are estimated to occur in up to 15% of patients with mCRC and V600E is the most common mutation. [1-3,12-14] The BRAFTOVI Triplet and Doublet were generally well-tolerated with no unexpected toxicities. The safety profiles of the BRAFTOVI Triplet and Doublet were consistent with prior reported experience with each regimen and with effects of MEK, RAF and EGFR therapies. In March 2019, the National Comprehensive Cancer Network® (NCCN®) updated their Clinical Practice Guidelines in Oncology for Colon and Rectal Cancer to include BRAFTOVI in combination with MEKTOVI and an anti-EGFR antibody as a Category 2A treatment for patients with BRAFV600E-mutant mCRC, after failure of one or two prior lines of therapy for metastatic disease. The NCCN based their recommendation on data from the safety lead-in of the BEACON CRC trial. On August 7, 2018, Array announced that the FDA granted Breakthrough Therapy Designation to BRAFTOVI, in combination with MEKTOVI and ERBITUX for the treatment of patients with BRAFV600E-mutant mCRC as detected by an FDA-approved test, after failure of one to two prior lines of therapy for metastatic disease. The triplet combination of BRAFTOVI, MEKTOVI and ERBITUX for the treatment of patients with BRAFV600E-mutant mCRC is investigational and not approved by the FDA. Conference Call Information
Webcast, Replay and Conference Call Slides: https://edge.media-server.com/m6/p/vth2rcxk About Colorectal Cancer About BEACON CRC The triplet combination of BRAFTOVI, MEKTOVI and ERBITUX for the treatment of patients with BRAFV600E-mutant mCRC is investigational and not approved by the FDA. About BRAFTOVI + MEKTOVI Array has exclusive rights to BRAFTOVI and MEKTOVI in the U.S. and Canada. Array has granted Ono Pharmaceutical Co. Ltd., exclusive rights to commercialize both products in Japan and South Korea, Medison exclusive rights to commercialize both products in Israel and Pierre Fabre exclusive rights to commercialize both products in all other countries, including Europe, Latin American and Asia (excluding Japan and South Korea). BRAFTOVI + MEKTOVI have received regulatory approval in the United States, European Union, Australia and Japan. The Swiss Medicines Agency (Swissmedic) is currently reviewing the Marketing Authorization Applications for BRAFTOVI and MEKTOVI submitted by Pierre Fabre. Indications and Usage Limitations of Use: BRAFTOVI is not indicated for the treatment of patients with wild-type BRAF melanoma. BRAFTOVI + MEKTOVI Important Safety Information Warnings and Precautions Tumor Promotion in BRAF Wild-Type Tumors: Confirm evidence of BRAFV600E or V600K mutation prior to initiating BRAFTOVI. Cardiomyopathy, manifesting as left ventricular dysfunction associated with symptomatic or asymptomatic decreases in ejection fraction, has been reported in patients. In the COLUMBUS trial, cardiomyopathy occurred in 7% and Grade 3 left ventricular dysfunction occurred in 1.6% of patients. Cardiomyopathy resolved in 87% of patients. Assess left ventricular ejection fraction by echocardiogram or MUGA scan prior to initiating treatment, 1 month after initiating treatment, and then every 2 to 3 months during treatment. Safety has not been established in patients with a baseline ejection fraction that is either below 50% or below the institutional lower limit of normal. Patients with cardiovascular risk factors should be monitored closely. Venous Thromboembolism (VTE): In the COLUMBUS trial, VTE occurred in 6% of patients, including 3.1% of patients who developed pulmonary embolism. Hemorrhage: In the COLUMBUS trial, hemorrhage occurred in 19% of patients and ≥ Grade 3 hemorrhage occurred in 3.2% of patients. Fatal intracranial hemorrhage in the setting of new or progressive brain metastases occurred in 1.6% of patients. The most frequent hemorrhagic events were gastrointestinal, including rectal hemorrhage (4.2%), hematochezia (3.1%), and hemorrhoidal hemorrhage (1%). Ocular Toxicities: In the COLUMBUS trial, serous retinopathy occurred in 20% of patients; 8% were retinal detachment and 6% were macular edema. Symptomatic serous retinopathy occurred in 8% of patients with no cases of blindness. RVO is a known class-related adverse reaction of MEK inhibitors and may occur in patients treated with MEKTOVI in combination with encorafenib. In patients with BRAF mutation-positive melanoma across multiple clinical trials, 0.1% of patients experienced retinal vein occlusion (RVO). The safety of MEKTOVI has not been established in patients with a history of RVO or current risk factors for RVO including uncontrolled glaucoma or a history of hyperviscosity or hypercoagulability syndromes. Perform ophthalmological evaluation for patient-reported acute vision loss or other visual disturbance within 24 hours. Permanently discontinue MEKTOVI in patients with documented RVO. In COLUMBUS, uveitis, including iritis and iridocyclitis was reported in 4% of patients. Assess for visual symptoms at each visit. Perform ophthalmological evaluation at regular intervals and for any visual disturbances, and to follow new or persistent ophthalmologic findings. Interstitial Lung Disease (ILD): ILD, including pneumonitis occurred in 0.3% of patients with BRAF mutation-positive melanoma across multiple clinical trials. Assess new or progressive unexplained pulmonary symptoms or findings for possible ILD. Hepatotoxicity: In the COLUMBUS trial, the incidence of Grade 3 or 4 increases in liver function laboratory tests was 6% for alanine aminotransferase (ALT) and 2.6% for aspartate aminotransferase (AST), and 0.5% for alkaline phosphatase. Monitor liver laboratory tests before and during treatment and as clinically indicated. Rhabdomyolysis: In the COLUMBUS trial, elevation of laboratory values of serum creatine phosphokinase (CPK) occurred in 58% of patients. Rhabdomyolysis was reported in 0.1% of patients with BRAF mutation-positive melanoma across multiple clinical trials. Monitor CPK and creatinine levels prior to initiating MEKTOVI, periodically during treatment, and as clinically indicated. QTc Prolongation: BRAFTOVI is associated with dose-dependent QTc interval prolongation in some patients. In the COLUMBUS trial, an increase in QTcF to > 500 ms was measured in 0.5% (1/192) of patients. Monitor patients who already have or who are at significant risk of developing QTc prolongation. Correct hypokalemia and hypomagnesemia prior to and during BRAFTOVI administration. Withhold, reduce dose, or permanently discontinue for QTc > 500 ms. Embryo-Fetal Toxicity: BRAFTOVI or MEKTOVI can cause fetal harm when administered to pregnant women. BRAFTOVI can render hormonal contraceptives ineffective. Non-hormonal contraceptives should be used during treatment and for at least 30 days after the final dose for patients taking BRAFTOVI + MEKTOVI. Adverse Reactions In the COLUMBUS trial, the most common laboratory abnormalities (≥20%, all Grades): included increased creatinine, increased CPK, increased gamma glutamyl transferase, anemia, increased ALT, hyperglycemia, increased AST, and increased alkaline phosphatase. Drug Interactions Please see full Prescribing Information for BRAFTOVI and full Prescribing Information for MEKTOVI for additional information. [17-18] You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Array at 1-844-Rx-Array (1-844-792-7729). About Array BioPharma References ® National Comprehensive Cancer Network, Inc. 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. Array BioPharma Forward-Looking Statement BRAFTOVI® and MEKTOVI® are registered trademarks of Array BioPharma Inc. in the United States and various other countries. Erbitux® is a registered trademark of Eli Lilly and Company. Vitrakvi® is a registered trademark of Bayer AG. All trademarks are properties of their respective owners. CONTACTS: Media
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