On May 18, 2016 Array BioPharma (NASDAQ: ARRY) reported that they will present additional data on their late-stage candidates binimetinib and encorafenib in NRAS-mutant melanoma and BRAF-mutant colorectal cancer, respectively, at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois on June 3-7 (Press release, Array BioPharma, MAY 18, 2016, View Source;p=RssLanding&cat=news&id=2169509 [SID:1234512536]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We look forward to presenting data at ASCO (Free ASCO Whitepaper) from our pivotal NEMO trial of binimetinib in NRAS-mutant melanoma, which met its primary endpoint of progression free survival (PFS), and plan to submit a New Drug Application (NDA) for binimetinib next month," said Ron Squarer, Chief Executive Officer of Array BioPharma. "Importantly, in the pre-specified sub-group of patients who received prior treatment with immunotherapy, including ipilimumab and nivolumab, median PFS was 5.5 months for patients treated with binimetinib compared to 1.6 months for patients treated with dacarbazine. These results are encouraging given the limited treatment options available to patients with NRAS-mutant melanoma beyond immunotherapy."

"We are also pleased to share results from our Phase 2 trial of encorafenib and cetuximab containing-regimens in BRAF-mutant colorectal cancer patients who have progressed after one or more prior therapies," added Mr. Squarer. "Data from this study suggest that median overall survival (OS) for these patients may exceed one year which is substantial when compared to historical published benchmarks for this population, which range between four to six months. We expect to present updated OS data from this trial at ASCO (Free ASCO Whitepaper) and plan to initiate a global Phase 3 trial in BRAF-mutant colorectal cancer later this year."

BINIMETINIB

In the Phase 3 NEMO (NRAS MELANOMA AND MEK INHBITOR) trial, 402 patients with NRAS-mutant melanoma were randomized 2:1 to receive binimetinib or dacarbazine, respectively. Eighty-five of the 402 patients received prior treatment with immunotherapy.

The primary endpoint of PFS was met, with a hazard ratio of 0.62, [95% CI 0.47-0.80] and a p-value of less than 0.001. The median PFS on the binimetinib arm was 2.8 months versus 1.5 months on the dacarbazine arm.
Importantly, an improvement in median PFS in binimetinib-treated patients was observed in the pre-specified sub-group of patients who received prior treatment with immunotherapy. The median PFS on the binimetinib arm was 5.5 months versus 1.6 months on the dacarbazine arm [HR=0.46 (95% CI 0.26-0.81)].
Confirmed overall response rate (ORR) and disease control rate (DCR) were 15 percent (95% CI, 11-20 percent) and 58 percent (95% CI, 52-64 percent) for all patients receiving binimetinib, respectively, versus 7 percent (95% CI, 3-13 percent) and 25 percent (95% CI, 18-33 percent) for patients receiving dacarbazine, respectively.
Grade 3/4 adverse events (AEs) reported in greater than or equal to 5 percent of patients receiving binimetinib included increased creatine phosphokinase (CPK) and hypertension.
Array expects to present additional OS data at ASCO (Free ASCO Whitepaper).
Data from the Phase 3 study will be featured during an oral presentation on Monday, June 6, 1:15 p.m. CT:

Abstract 9500: Results of NEMO: A phase III trial of binimetinib (BINI) vs dacarbazine (DTIC) in NRAS-mutant cutaneous melanoma
Presenter: Reinhard Dummer, M.D.
ENCORAFENIB

In the Phase 2 BRAF-mutant colorectal cancer trial, 102 patients were randomized 1:1 to receive encorafenib and cetuximab with or without alpelisib:

Median PFS was 5.4 months and 4.2 months for the triplet and doublet regimens, respectively.
An early analysis of median OS exceeded one year for the triplet regimen and was not reached for the doublet regimen. Updated interim median OS analysis for both regimens will be presented at ASCO (Free ASCO Whitepaper).
Confirmed ORR was 27 percent (95% CI, 16-41 percent) for the triplet regimen and 22 percent (95% CI, 12-36 percent) for the doublet regimen.
Grade 3/4 AEs occurring in greater than 10 percent of patients in either arm included anemia, hyperglycemia and increased lipase.
Historical published PFS and OS results after first-line treatment range between 1.8 to 2.5 months and four to six months, respectively, and published response rates from various studies in this population range between 6 percent to 8 percent.

Data from the Phase 2 study will be presented on Saturday, June 4, 8:00 – 11:30 a.m. CT:

Abstract 3544: Phase 2 results: encorafenib (ENCO) and cetuximab (CETUX) with or without alpelisib (ALP) in patients with advanced BRAF-mutant colorectal cancer (BRAFm CRC)
Presenter: Josep Tabernero, M.D., Ph.D.
Additional data from Array BioPharma and partner compounds will also be presented at ASCO (Free ASCO Whitepaper) across a variety of tumor types.

All abstracts can be accessed through the ASCO (Free ASCO Whitepaper) website, View Source After the presentations and posters are public, they will be available as PDFs on Array’s website at www.arraybiopharma.com.

About NRAS-Mutant Melanoma
Activating NRAS mutations are present in up to 20 percent of patients with metastatic melanoma, and is a poor prognostic indicator for these patients. Treatment options for this population remain limited beyond immunotherapy, and patients face poor clinical outcomes and high mortality.

About BRAF-Mutant Colorectal Cancer
Colorectal cancer is the third most common cancer among men and women in the United States, with more than 134,000 new cases and nearly 50,000 deaths from the disease projected in 2016.

About Binimetinib and Encorafenib
MEK and BRAF 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, such as melanoma, non-small cell lung, colorectal and thyroid cancers. Binimetinib is a late-stage small molecule MEK inhibitor and encorafenib is a late-stage small molecule BRAF inhibitor, both of which target key enzymes in this pathway.

Binimetinib and encorafenib are being studied in Phase 3 trials in advanced cancer patients, including: NRAS-mutant melanoma (NEMO, binimetinib single agent) and BRAF-mutant melanoma in combination with encorafenib (COLUMBUS, binimetinib and encorafenib). Activating BRAF mutations are present in approximately 50 percent of patients with metastatic melanoma. NRAS-mutant melanoma represents the first potential indication for binimetinib, with a projected regulatory filing estimated in the first half of 2016. Array also projects COLUMBUS top-line results availability during the third quarter of 2016. In addition, Array plans to initiate a Phase 3 global registration trial in patient with BRAF-mutant colorectal cancer later this year.