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Array BioPharma Submits New Drug Applications To FDA For Binimetinib And Encorafenib In Advanced Melanoma

BRAF-mutant advanced, unresectable or metastatic melanoma. The submissions are supported by data from the pivotal Phase 3 COLUMBUS study, which showed that patients who received binimetinib and encorafenib had a significantly longer progression free survival (PFS) compared to patients receiving vemurafenib.

"The totality of the COLUMBUS results, including estimated progression free survival, objective response rate, dose intensity and tolerability of the combination, provide a strong and consistent theme across multiple endpoints for this study," said Ron Squarer, Chief Executive Officer, Array BioPharma. "We look forward to working with the FDA as they review the NDA and, if approved, hope the combination of binimetinib and encorafenib will become a new option for patients with BRAF-mutant advanced melanoma."

COLUMBUS Results
As presented at the 2016 Society for Melanoma Research Annual Congress, results from Part 1 of the COLUMBUS study showed that COMBO450 significantly extend PFS in patients with advanced BRAF-mutant melanoma, with a PFS of 14.9 months compared with 7.3 months observed with vemurafenib [hazard ratio (HR) 0.54, (95% CI 0.41-0.71, P<0.001)]. As part of the trial design, the primary analysis was based on a Blinded Independent Central Review (BICR) of patient scans, while results by local review at the investigative site were also analyzed. The table below outlines the median PFS (mPFS) results, as determined by both assessments, for COMBO450 versus vemurafenib, COMBO450 versus encorafenib, and encorafenib versus vemurafenib:



mPFS BICR


mPFS Local Review

COMBO450 vs. Vemurafenib


COMBO450

Vemurafenib


COMBO450

Vemurafenib


14.9 months

7.3 months


14.8 months

7.3 months


HR (95% CI): 0.54 (0.41-0.71); P<0.001


HR (95% CI): 0.49 (0.37-0.64); P<0.001


COMBO450 vs. Encorafenib


COMBO450

Encorafenib


COMBO450

Encorafenib


14.9 months

9.6 months


14.8 months

9.2 months


HR (95% CI): 0.75 (0.56-1.00); P=0.051


HR (95% CI): 0.68 (0.52-0.90); P=0.006


Encorafenib vs. Vemurafenib


Encorafenib

Vemurafenib


Encorafenib

Vemurafenib


9.6 months

7.3 months


9.2 months

7.3 months


HR (95% CI): 0.68 (0.52-0.90); P=0.007


HR (95% CI): 0.70 (0.54-0.91); P=0.008

In this study, COMBO450 was generally well-tolerated, with a median duration of treatment of 51 weeks and median relative dose intensity for encorafenib and binimetinib of 100% and 99.6%, respectively. Grade 3/4 adverse events (AEs) that occurred in more than 5% of patients receiving COMBO450 were increased blood creatine phosphokinase (CK) (9%), increased gamma-glutamyltransferase (GGT) (7%) and hypertension (6%). The incidence of any grade of AEs of special interest, defined based on toxicities commonly associated with commercially available MEK+BRAF-inhibitor treatments for patients receiving COMBO450 included: rash (23%), pyrexia (18%), retinal pigment epithelial detachment (13%) and photosensitivity (5%). Full safety results of COLUMBUS Part 1 were presented at the 2016 Society for Melanoma Research Annual Congress.

COLUMBUS Part 2 was designed specifically to assess the contribution of binimetinib to the combination of binimetinib and encorafenib by reducing the dose of encorafenib to 300mg in the combination arm to allow for a comparison...


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