Array Biopharma (ARRY), Pierre Fabre Announce Presentation of Binimetinib Combo Phase 3 Data in BRAF-Mutant Melanoma

November 9, 2016 10:02 AM EST

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Array BioPharma (Nasdaq: ARRY) and Pierre Fabre jointly announced new results from the pivotal Phase 3 COLUMBUS trial of binimetinib plus encorafenib (bini/enco) treatment in BRAF-mutant melanoma patients at the Society for Melanoma Research Annual Congress. The study met its primary endpoint, with the combination of bini/enco significantly improving progression free survival (PFS) compared with vemurafenib, a BRAF inhibitor, alone. The combination of bini/enco was generally well-tolerated and reported adverse events (AEs) were overall consistent with previous published clinical trial results for the bini/enco combination in BRAF-mutant melanoma patients.

"The results presented today from the COLUMBUS trial, including estimated progression free survival, objective response rate, dose intensity and tolerability of the combination, provide a strong and consistent theme across multiple endpoints, underscoring the promise of binimetinib plus encorafenib as a potential, attractive treatment option for patients diagnosed with BRAF-mutant melanoma," said Keith T. Flaherty, M.D., Director of the Termeer Center for Targeted Therapy, Massachusetts General Hospital and Professor of Medicine, Harvard Medical School.

In the analysis of the primary endpoint, the median PFS (mPFS) for patients treated with the combination of bini/enco was 14.9 months versus 7.3 months for patients treated 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 chart below outlines the mPFS results, as determined by both assessments, for the combination of bini/enco versus vemurafenib, bini/enco versus encorafenib, and encorafenib versus vemurafenib:

mPFS BICR

mPFS Local Review

Bini/Enco vs. Vemurafenib

Bini/Enco

Vemurafenib

Bini/Enco

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

Bini/Enco vs. Encorafenib

Bini/Enco

Encorafenib

Bini/Enco

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

The combination of bini/enco also demonstrated an improvement in confirmed overall response rate (ORR; complete response plus partial response), as well as favorable median duration of exposure, high median dose intensity and consistent activity in patients with prior immunotherapy treatment as well as an advantage in terms of maintaining quality of life for patients.

Confirmed ORR BICR

Confirmed ORR Local Review

Bini/Enco

63% (95% CI: 56-70%)

75% (95% CI: 68-81%)

Vemurafenib

40% (95% CI: 33-48%)

49% (95% CI: 42-57%)

Encorafenib

51% (95% CI: 43-58%)

58% (95% CI: 50-65%)

  • Median duration of exposure was approximately 51 weeks for patients receiving bini/enco, versus 31 weeks and 27 weeks for the encorafenib and vemurafenib monotherapy arms, respectively
  • Median dose intensity for patients treated with bini/enco was 100% (encorafenib) and 99.6% (binimetinib)
  • 5% of bini/enco patients had received prior treatment with check-point inhibitors, including ipilimumab, anti-PD-1 and/or anti-PD-L1 therapies, and the observed clinical activity for these patients was consistent with that of bini/enco patients who had not received prior immunotherapy
  • The Quality of Life (QoL) measures were consistent between two scales and showed an advantage in terms of maintaining quality of life for patients receiving bini/enco compared to patients treated with either encorafenib or vemurafenib single agent therapy. The QoL scales used were the EORTC Quality of Life Questionnaire Core 30 and FACT-Melanoma Scale Score (Functional Assessment of Cancer Therapy).

The combination of bini/enco was generally well-tolerated and reported AEs were overall consistent with previous bini/enco combination clinical trial results in BRAF-mutant melanoma patients.

  • Grade 3/4 AEs which occurred in more than 5% of patients receiving bini/enco included increased gamma-glutamyltransferase (GGT), increased blood creatine phosphokinase (CK), and hypertension
  • The incidence of AEs of special interest (toxicities commonly associated with commercially available MEK+BRAF-inhibitor treatments), for patients receiving bini/enco included (% of patients): rash (23%), pyrexia (18%), retinal pigment epithelial detachment (13%) and photosensitivity (5%)

"The robust PFS benefit and tolerability observed with binimetinib plus encorafenib in COLUMBUS suggest the combination represents a potential important addition to the MEK/BRAF treatment landscape for patients with BRAF-mutant melanoma," said Victor Sandor, Chief Medical Officer, Array BioPharma. "We are preparing these data for regulatory submission in 2017."

Frédéric Duchesne, Chief Executive Officer Pharmaceutical Division, Pierre Fabre remarked, "We are very pleased with the promising results and look forward to the possibility that, if approved, the combination of encorafenib plus binimetinib could offer a new treatment option for patients suffering from this devastating disease."



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