Array BioPharma Announces Presentation of Updated Overall Survival from the Phase 3 COLUMBUS Trial of BRAFTOVI + MEKTOVI in advanced BRAF-mutant Melanoma at 2019 ASCO Annual Meeting
BOULDER, Colo., May 29, 2019 /PRNewswire/ -- Array BioPharma, Inc. (Nasdaq: ARRY) announced that that it will present data from the Phase 3 COLUMBUS Trial of BRAFTOVI + MEKTOVI in advanced BRAF-mutant melanoma in an oral poster discussion on June 3, 2019, at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois. Landmark overall survival (OS) and progression-free survival (PFS), as well as subgroup analyses and updated safety and tolerability, will be presented.
"We are pleased to report a 4-year landmark analysis of the long-term benefit of BRAFTOVI + MEKTOVI from the COLUMBUS trial," said Ron Squarer, Chief Executive Officer. "Both the overall survival and progression-free survival data remain consistent with prior reports and continue to represent new benchmarks for BRAF + MEK inhibitor combinations in the treatment of BRAFV600-mutant advanced melanoma. We remain steadfastly committed to developing products that treat cancers in dire need of effective therapies."
Across arms, median follow-up for OS was 48.6 months, with a median OS of 33.6 months (95% CI, 24.4–39.2) for BRAFTOVI, 450 mg daily + MEKTOVI, 45 mg twice daily, compared to 16.9 months (95% CI, 14.0–24.5) for vemurafenib, consistent with prior readouts. Compared to vemurafenib, BRAFTOVI, 450 mg daily + MEKTOVI, 45 mg twice daily, decreased the risk of death by 39% (HR, 0.61 [95% CI, 0.48–0.79]).
Updated median progression-free survival (PFS) also remained consistent and was 14.9 months (95% CI, 11.0–20.2) with BRAFTOVI, 450 mg daily + MEKTOVI, 45 mg twice daily, compared to 7.3 months (95% CI, 5.6–8.2) with vemurafenib (HR, 0.52 [95% CI, 0.40–0.67]).
The abstracts can be accessed through the ASCO website, http://abstract.asco.org/. Following the poster presentation on Monday, June 3, 2019, the poster will be available as a PDF on Array's website at www.arraybiopharma.com.
About BRAF-mutant Metastatic Melanoma
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.
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.
Please see full Prescribing Information for BRAFTOVI and full Prescribing Information for MEKTOVI for additional information. [6,7] 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
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.
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SOURCE Array BioPharma Inc.
Company Codes: NASDAQ-NMS:ARRY