On February 9, 2017 Boehringer Ingelheim reported the initiation of a Phase II trial of afatinib* (Giotrif) in combination with pembrolizumab (Keytruda) for patients with locally advanced or metastatic squamous cell carcinoma (SqCC) of the lung (Press release, Boehringer Ingelheim, FEB 9, 2017, View Source [SID1234517687]).

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!

Benjamin Levy, MD, Clinical Director, Sidney Kimmel Cancer Center, Johns Hopkins Medicine at Sibley Memorial Hospital Washington DC, USA said, "Given the complexity of tumours and their ability to evade immune destruction, combination approaches rooted in both clinical and scientific rationale are desperately needed. Bringing together two drugs, afatinib and pembrolizumab, which have each demonstrated meaningful activity and survival advantages in advanced stage squamous cell lung cancer patients, is an attractive strategy that needs to be further investigated as a treatment combination. The potential synergy in these agents will hopefully advance care and therapeutic options for this group of patients."

Afatinib is approved in the EU (Giotrif), US (Gilotrif) and other markets in patients with advanced SqCC of the lung whose disease has progressed on or after (EU label) / after (US label) treatment with platinum-based chemotherapy.

Pembrolizumab is approved in the US, EU, Japan and other markets for the treatment of previously-untreated patients with metastatic non-small cell lung cancer (NSCLC) whose tumours have high PD-L1 expression (tumour proportion score (TPS) >50%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumour aberrations. Pembrolizumab is also indicated for the treatment of previously-treated patients with metastatic NSCLC whose tumours express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy.

The trial is being conducted in collaboration with a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the US and Canada) and the combination of afatinib and pembrolizumab studied in this trial is currently not an approved treatment regimen in the studied indication.


Dr Victoria Zazulina
Dr Victoria Zazulina, Medical Head, Solid Tumour Oncology, Boehringer Ingelheim said, "We are excited to collaborate with MSD and launch this trial, allowing us to gain further insights into the opportunities around treatment of squamous cell carcinoma of the lung. Around the world, patients with this type of cancer are already benefitting from anti-PD-1 therapies and afatinib, the only oral tyrosine kinase inhibitor (TKI) used in this indication. It is intriguing to combine both approaches in an attempt to improve the outcomes for patients with squamous lung cancer and equip physicians with new options."

The Phase II trial will include approximately 60 patients who have progressed or relapsed on or after prior platinum-based chemotherapy, and who have not previously received therapy with an anti-PD-1 therapy, a PD-L1/L2 antibody, or other checkpoint inhibitor or anti-EGFR targeted therapy. The trial aims to measure the decrease in tumour size (primary endpoint; objective response rate) and will confirm the dose of afatinib in combination with the standard dose of pembrolizumab, as well as the tolerability of this new regimen. In addition, it will evaluate anti-tumour activity in terms of disease control, duration of response, progression-free survival (PFS) and overall survival (OS).

SqCC of the lung is the second largest sub-type of NSCLC and represents approximately 20-30% of NSCLC cases.1,2 Patients with advanced SqCC of the lung typically have a poor prognosis and the median overall survival after diagnosis is around one year.3,4

Afatinib is also approved in over 70 countries for the first-line treatment of EGFR mutation-positive NSCLC and continues to be more broadly studied beyond the approved indications.

Notes to editors

Intended audiences
This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business.

About Afatinib
Afatinib* is approved in the EU (Giotrif), US (Gilotrif) and other markets in patients with advanced SqCC of the lung whose disease has progressed on or after (EU-label) / after (US label) treatment with platinum-based chemotherapy.

Approval of afatinib in this indication is based on results of the LUX-Lung 8 study, which showed a significantly improved OS and PFS compared to Tarceva (erlotinib) in patients with SqCC of the lung.5
LUX-Lung 8 is part of the LUX-Lung programme – the largest collection of clinical trials of any EGFR TKI, with over 3,760 patients across eight studies conducted across the world.
Afatinib is also approved in over 70 countries for the first-line treatment of EGFR mutation-positive NSCLC.

Approval of afatinib in this indication was based on the primary endpoint of PFS from the LUX-Lung 3 clinical trial where afatinib significantly delayed tumour growth when compared to standard chemotherapy. 6
In addition, afatinib is the first treatment to have shown an OS benefit for patients with specific types of EGFR mutation-positive NSCLC compared to chemotherapy.7 A significant OS benefit was demonstrated independently in the LUX-Lung 3 and 6 trials for patients with the most common EGFR mutation (del19) compared to chemotherapy.7
Most recently in the LUX-Lung 7 trial, a reduction in the risk of death was observed for patients treated with afatinib versus Iressa (gefitinib), in the first-line treatment of patients with EGFR mutation-positive advanced NSCLC, without reaching significance.8
View Source

On February 9, 2017 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age-related macular degeneration and fibrotic diseases, reported top-line results from a randomized Phase 2 clinical trial of TRC105 in recurrent glioblastoma (GBM) funded and conducted by the Clinical Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) (Press release, Tracon Pharmaceuticals, FEB 9, 2017, View Source [SID1234517685]).

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!

In the trial, TRC105 combined with Avastin (bevacizumab) was compared to single agent Avastin in a total of 101 patients with recurrent GBM following chemoradiation. The trial was designed to detect a three-month improvement in progression free survival (PFS), the primary endpoint, from the expected value of 3.45 months with single agent Avastin. Top-line data indicate that the combination of TRC105 and Avastin did not improve median PFS versus single agent Avastin in recurrent GBM patients, although the combination was associated with a non-significant increase in overall survival. Detailed data and the associated correlative analyses are expected to be presented at an oncology conference later this year.

"Glioblastoma is a very challenging indication for drug development," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "We are grateful to the National Cancer Institute for sponsoring the trial and to the patients and providers who participated, and look forward to the detailed survival analysis from this trial, as well as data from multiple company-sponsored trials of TRC105 in other indications later this year."

About TRC105 and other Endoglin Antibodies

TRC105 is a novel, clinical stage antibody to endoglin, a protein overexpressed on proliferating endothelial cells that is essential for angiogenesis, the process of new blood vessel formation. TRC105 is currently being studied in one Phase 3 and multiple Phase 2 clinical trials sponsored by TRACON or the National Cancer Institute for the treatment of solid tumor types in combination with VEGF inhibitors. The ophthalmic formulation of TRC105, DE-122, is currently in a Phase 1/2 trial for patients with wet AMD. TRC205, a second generation antibody to endoglin, is undergoing preclinical testing in models of fibrosis. For more information about the clinical trials, please visit TRACON’s website at View Source

On February 9, 2017 AVEO Oncology (NASDAQ:AVEO) reported clinical and regulatory updates for its lead drug candidate, tivozanib, an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) (Press release, AVEO, FEB 9, 2017, View Source [SID1234517674]).

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!

The Company announced today that its pivotal, Phase 3 TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced renal cell carcinoma (RCC), is enrolling substantially ahead of schedule. The Company now expects TIVO-3 to complete enrollment in June 2017, ahead of its prior guidance of August 2017. Because the study is event driven the Company is not revising the anticipated time to topline data at this time, which is currently expected in the first quarter of 2018. TIVO-3 is expected to undergo a pre-planned futility analysis around midyear. The TIVO-3 trial, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of RCC, is designed to support first and third line indications for tivozanib in the U.S.

The Company also announced today that the Phase 1/2 AVEO-sponsored TiNivo trial evaluating tivozanib in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, Opdivo (nivolumab), in advanced RCC, is scheduled to open sites for enrollment in early March, with dosing of the first patient expected in the same timeframe. The company received approval by the French National Agency for Medicines and Health Products Safety (ANSM) to initiate the study and is currently labelling the nivolumab supply provided by Bristol-Myers Squibb for use in the trial. The study, which will be led by the Institut Gustave Roussy in Paris, is under the direction of Professor Bernard Escudier, MD, Chairman of the Genitourinary Oncology Committee. The Phase 1 trial will evaluate the safety of tivozanib in combination with nivolumab at escalating doses of tivozanib and, assuming favorable results, is expected to be followed by an expansion Phase 2 cohort at the established combination dose.

AVEO also announced today that its European licensee for tivozanib, EUSA Pharma, a specialty pharmaceutical company with a focus on oncology and oncology supportive care, has received the Day 180 List of Outstanding Issues (LOI) from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). The Day 180 LOI signifies that the Marketing Authorization Application is not approvable at the present time, and outlines outstanding deficiencies, which are then required to be satisfactorily addressed in an oral explanation and/or in writing prior to a final application decision. EUSA has informed AVEO that it expects to submit written responses to the Day 180 LOI in April 2017, and the EMA has tentatively scheduled EUSA to provide an oral explanation to the CHMP at its May 2017 meeting.

"We continue to execute on the TIVO-3 and TiNivo studies in our effort to complete our U.S. pivotal clinical strategy, as well as support EUSA Pharma in its response to European regulators," said Michael Bailey, president and chief executive officer of AVEO. "The rapid pace of enrollment in our TIVO-3 study is a testament to the broad level of support and enthusiasm for tivozanib among investigators. Fundamental to this drug candidate’s unique profile would be its potential to be safely combined with PD-1 immunotherapies, and we look forward to initial results from the Opdivo combination TiNivo study in RCC in the first half of 2017."

About Tivozanib

Tivozanib is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI). It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications. Tivozanib has been investigated in several tumors types, including renal cell, colorectal and breast cancers.

About the TIVO-3 Trial

The Phase 3 TIVO-3 trial is a pivotal, randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced renal cell carcinoma (RCC). The trial is expected to enroll approximately 322 patients with recurrent RCC who have failed at least two prior regimens, including VEGFR-TKI therapy (other than sorafenib). Eligible patients may also have received checkpoint inhibitor therapy in earlier lines of treatment. Patients will be randomized 1:1 to receive either tivozanib or sorafenib, with no crossover between arms. The primary endpoint of the study is progression free survival. Secondary endpoints include overall survival, overall response rate, and safety and tolerability. The TIVO-3 trial, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of RCC, is designed to support a first and third line indication for tivozanib in the U.S.

On Thursday 9, 2017 The Merck Foundation (Foundation), reported the selection of the six program sites and National Program Office forming the Alliance to Advance Patient-Centered Cancer Care (the Alliance) (Press release, Merck & Co, FEB 9, 2017, View Source [SID1234517673]). With $15 million in funding from the Foundation over five years, the Alliance aims to increase timely access to patient-centered cancer care for vulnerable and underserved populations in the United States.

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!

The following organizations have been selected based on a variety of criteria, including the technical merit of their proposed programs, their organizational capabilities and experience, relationships with community partners, and ability to promote sustainable improvements in the delivery of cancer care.

Grady Health System in Atlanta, Ga.;
The Johns Hopkins University in Baltimore, Md.;
Massachusetts General Hospital in Boston, Mass.;
Northwestern University in Chicago, Ill.;
Ohio State University in Columbus, Ohio; and
The University of Arizona in Tucson, Ariz.

The University of Michigan School of Nursing, in Ann Arbor, Mich., will serve as the Alliance’s National Program Office.

"With 1.7 million Americans newly diagnosed with cancer each year, there is a great need to improve the quality and delivery of patient-centered care to help address the significant challenges of those facing this diagnosis," said Julie L. Gerberding, chief patient officer, Merck and chief executive officer, Merck Foundation. "These superb program sites and the National Program Office should accelerate identification and uptake of innovations that benefit patients, improve health communications, and enhance the overall coordination of care."

Through an independent cross-site evaluation, the Foundation will evaluate the impact of the Alliance and its programs. The evaluation findings and lessons learned will be disseminated to promote best practices in patient-centered cancer care.

About The Merck Foundation

The Merck Foundation is a U.S.-based, private charitable foundation. Established in 1957 by Merck, a global health care leader, the Foundation is funded entirely by the company and is Merck’s chief source of funding support to qualified non-profit charitable organizations. Since its inception, the Merck Foundation has contributed more than $870 million to support important initiatives that address societal needs and are consistent with Merck’s overall mission to help the world be well. For more information, visit www.merckgiving.com.

On February 9, 2017 Array BioPharma Inc. (Nasdaq: ARRY), a biopharmaceutical company focused on the discovery, development and commercialization of targeted small molecule cancer therapies, reported results for its second quarter of fiscal 2017 and provided an update on the progress of its key clinical development programs (Press release, Array BioPharma, FEB 9, 2017, View Source [SID1234517672]).

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 were pleased to report that COLUMBUS met its primary endpoint and demonstrated a robust PFS benefit associated with the combination of binimetinib plus encorafenib versus vemurafenib in patients with BRAF-mutant melanoma," said Ron Squarer, Chief Executive Officer of Array BioPharma. "Following a pre-NDA meeting with the FDA, we expect to file an NDA for COLUMBUS in June or July."

KEY COMPANY AND PIPELINE UPDATES
Binimetinib (MEK162) and encorafenib (LGX818)
Novartis continues to substantially fund all ongoing trials with binimetinib and encorafenib that were active or planned as of the close of the Novartis Agreements in 2015, including the NEMO and COLUMBUS Phase 3 trials. Reimbursement revenue from Novartis was approximately $130 million for the previous 12 months, of which $27.9 million was recorded over the quarter ending December 31, 2016.

COLUMBUS: Global Phase 3 trial of binimetinib plus encorafenib versus vemurafenib in BRAF-mutant melanoma patients
In November 2016, results from the pivotal Phase 3 COLUMBUS trial of binimetinib plus encorafenib (bini/enco) treatment in BRAF-mutant melanoma patients were presented 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. 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), the ability to deliver a high dose intensity to the majority of patients 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 percent (encorafenib) and 99.6 percent (binimetinib).
5 percent 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 generally 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 adverse events (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 percent 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: rash (23 percent), pyrexia (18 percent), retinal pigment epithelial detachment (13 percent) and photosensitivity (5 percent).
In addition, following discussions with the Independent Data Monitoring Committee (DMC), COLUMBUS clinical investigators were instructed in January 2017 to notify all study participants of the results of the trial and to offer only vemurafenib patients alternative treatments with approved MEK/BRAF inhibitors. Array expects to file an NDA for COLUMBUS in June or July, with data from both Part 1 and Part 2 of the study. We believe Pierre Fabre remains on track to file the MAA during 2017. Binimetinib and encorafenib are investigational medicines and are not currently approved in any country.

Melanoma is the fifth most common cancer among men and the sixth most common cancer among women in the United States, with more than 87,000 new cases and over 9,700 deaths from the disease expected in 2017. Novel therapies that target the RAS-RAF-MEK-ERK pathway have a strong scientific rationale for activity in this disease, as up to 50 percent of patients with metastatic melanoma have activating BRAF mutations, the most common gene mutation in this patient population. Current marketed MEK/BRAF combination agents have a run rate approaching $1 billion in annual worldwide sales.

NEMO: Global Phase 3 trial of binimetinib versus dacarbazine in NRAS-mutant melanoma patients
In September 2016, Array announced that the FDA accepted its NDA for binimetinib in NRAS-mutant melanoma, with a target action date under the Prescription Drug User Fee Act (PDUFA) of June 30, 2017. Also, the binimetinib Marketing Authorization Application (MAA) submitted by Pierre Fabre was validated and is currently under evaluation by the Committee for Medicinal Products for Human Use (CHMP). The FDA indicated that it plans to hold an advisory committee meeting (ODAC) in the first half of 2017 as part of the review process.

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

BEACON CRC: Global Phase 3 trial of binimetinib, encorafenib and Erbitux (cetuximab) versus Erbitux in BRAF-mutant colorectal cancer (CRC) patients
Array is advancing BEACON CRC, a global Phase 3 trial of encorafenib and Erbitux (cetuximab), with or without binimetinib, versus standard of care in patients with BRAF-mutant CRC who have previously received first-or second-line systemic therapy. The study includes a safety lead-in with approximately 30 patients. Enrollment in the safety lead-in continues following a planned DMC review of the initial cohort. Array expects to complete patient enrollment with the safety lead-in in March and initiate randomization of patients in April. Array continues to expect early data from the triplet lead-in later this year.

BEACON CRC was initiated based on results from a Phase 2 study of the combination of encorafenib and cetuximab, with or without alpelisib, a selective PI3K alpha inhibitor, in patients with advanced BRAF-mutant CRC, which were presented at the 2016 ASCO (Free ASCO Whitepaper) meeting. In this study mOS for these patients exceeded one year, which is more than double several historical published benchmarks for this population.

Colorectal cancer is the second most common cancer among men and third most common cancer among women in the United States, with more than 135,000 new cases and more than 50,000 deaths from the disease projected in 2017. In the United States, BRAF mutations occur in 8 to 15 percent of patients with colorectal cancer and represent a poor prognosis for these patients.

New NF1 Study: Phase 2 trial of binimetinib in patients with Neurofibromatosis Type 1 (NF1)
In collaboration with Neurofibromatosis Consortium, Array is participating in a Phase 2 study of binimetinib in children and adults with NF1 associated Plexiform Neurofibromas. The study will enroll approximately 40 NF1 patients to determine the objective response to binimetinib defined as a 20 percent or greater tumor volume reduction by MRI. In addition, duration of response, assessment of quality of life, pain, functional outcomes, and safety and tolerability will be assessed.

Results from a prior Phase 1 NF1 trial of selumetinib, a MEK inhibitor also invented at Array, were recently published in the New England Journal of Medicine, supporting further study of a MEK inhibitor in this patient population.

Non-clinical studies with MEK/PD-1
Binimetinib Enhances a Programmed Cell Death Receptor 1 (PD-1) Inhibitor Anti-Tumor Activity in Immunocompetent Preclinical Models
Array is evaluating MEK’s contribution to immunotherapy in non-clinical cancer models, including models for CRC and pancreatic cancer.

In a CRC model, the combination of binimetinib with immunotherapy demonstrates enhanced tumor growth inhibition, providing support for the potential mechanistic synergies between immunotherapy and MEK inhibition.

In a pancreatic cancer model, the combination treatment group shows enhanced survival (i.e., PFS) with the addition of binimetinib to anti-PD-1 antibody treatment, compared to single agent anti-PD-1 treatment. Definitive tumor growth inhibition and survival studies in this model are ongoing.

Given the potential to improve clinical outcomes, as supported by these non-clinical studies, Array believes that MEK / anti-PD1 combinations are appropriate regimens to study in a number of cancer indications.

ARRY-382
Phase 1/2 dose escalation study advancing with ARRY-382, a colony-stimulating factor-1 receptor (CSF-1R) inhibitor, in combination with pembrolizumab, a PD-1 antibody, for the treatment of patients with advanced solid tumors
Array is advancing a Phase 1/2 dose escalation immuno-oncology trial of ARRY-382 in combination with pembrolizumab (Keytruda), a PD-1 antibody, in patients with advanced solid tumors. ARRY-382 is a wholly-owned, highly selective and potent, small molecule inhibitor of CSF-1R kinase activity.

Enrollment in the Phase 1 portion of the trial continues following a planned DMC review of the initial dose level. Array expects to complete the Phase 1 portion of the trial in March and to initiate Phase 2 expansions in melanoma and non-small lung cancer during April.

ARRY-797 (ARRY-371797)
Phase 2 trial in patients with LMNA A/C-related dilated cardiomyopathy (LMNA-related DCM)
Based on data to date from a Phase 2 study of ARRY-797, an oral, selective p38 mitogen-activated protein kinase inhibitor, in patients with LMNA-related DCM a rare, degenerative cardiovascular disease caused by mutations in the LMNA gene and characterized by poor prognosis. Array plans to initiate a Phase 3 trial of ARRY-797 this summer as we evaluate options regarding the asset, including advancing it internally, partnering the program for further development and commercialization or creating a separate company.

SELUMETINIB
Phase 1 trial results in pediatric patients with neurofibromatosis type 1 (NF1) and plexiform neurofibromas published in the New England Journal of Medicine
In a Phase 1 clinical trial of selumetinib, a MEK inhibitor, children with the common genetic disorder neurofibromatosis type 1 (NF1) and plexiform neurofibromas, tolerated selumetinib and, in most cases, responded to it with tumor shrinkage. NF1 affects 1 in 3,000 people. The study results were published on December 29, 2016, in The New England Journal of Medicine. Selumetinib is being explored as a treatment option in registration-enabling studies in patients with NF1 and patients with differentiated thyroid cancer. Array licensed exclusive worldwide rights to selumetinib to AstraZeneca and is entitled to future potential milestones and royalties on product sales.

The trial, which included 24 patients recruited between September 2011 and February 2014, was led by the National Cancer Institute’s Pediatric Oncology Branch. Plexiform neurofibromas develop in up to 50 percent of people with NF1. The majority of these tumors, which can cause significant pain, disability, and disfigurement, are diagnosed in early childhood and grow most rapidly prior to adolescence. Complete surgical removal of the tumors is rarely feasible, and incompletely resected tumors tend to grow back.

The primary aim of this clinical trial was to evaluate the toxicity and safety of selumetinib in patients with NF1 and inoperable plexiform neurofibromas, and, encouragingly, most of the selumetinib-related toxic effects were mild. At present, no therapies are considered effective for NF1-related large plexiform neurofibromas, but, in this trial, partial responses, meaning 20 percent or more reduction in tumor volume, were observed in over 70 percent of the patients.

Responses were observed in tumors that were previously growing at a rate of greater than 20 percent per year, as well as in non-progressing lesions. Tumor shrinkage was maintained long term, for approximately two years, and as of early 2016, no disease progression had been observed in any trial participant. Patients remained on study for as long as four years. Additionally, anecdotal evidence of clinical improvement, including a decrease in tumor-related pain, improvement in motor function, and decreased disfigurement, was reported.

FINANCIAL HIGHLIGHTS
Second Quarter of Fiscal 2017 Compared to First Quarter of Fiscal 2017 (Sequential Quarters Comparison)

Revenue for the second quarter of fiscal 2017 was $44.5 million, compared to $39.3 million for the prior sequential quarter, mainly driven by earning a $6.0 million milestone from Loxo Oncology for the advancement of larotrectinib (LOXO-101), the pan-Trk inhibitor for cancer and a $2.5 million milestone from Roche for the advancement of danoprevir, the NS3/4A protease inhibitor for Hepatitis C.
Cost of partnered programs for the second quarter of fiscal 2017 was $9.0 million, compared to $8.8 million for the prior quarter.
Research and development expense was $46.5 million, compared to $46.6 million in the prior quarter.
Net loss for the second quarter was $23.3 million, or ($0.14) per share, and was $28.6 million, or ($0.20) per share in the prior quarter. The decrease in net loss was primarily due to increased milestone revenue.
Cash, Cash Equivalents and Marketable Securities as of December 31, 2016 were $214.8 million; this includes net proceeds of $124.2 million from the public offering of 21,160,000 shares of Array common stock in October 2016.
Second Quarter of Fiscal 2017 Compared to Second Quarter of Fiscal 2016 (Prior Year Comparison)

Revenue for the second quarter of fiscal 2017 increased $9.1 million compared to the same quarter of fiscal 2016. The increase was primarily due to earning a milestone from Loxo Oncology for the advancement of larotrectinib (LOXO-101), the TRK inhibitor for cancer and a milestone from Roche for the advancement of danoprevir, the NS3 protease inhibitor for Hepatitis C.
Cost of partnered programs increased $3.4 million compared to the second quarter of fiscal 2016. The increase was primarily due to costs incurred on the BEACON CRC trial.
Research and development expense increased $5.1 million, compared to the second quarter of fiscal 2016. The increase was due to binimetinib and encorafenib expenses as we transitioned activity from the "Novartis Agreements."
Net loss for the second quarter of fiscal 2017 was $23.3 million, or ($0.14) per share, and was $24.2 million, or ($0.17) per share, for the same quarter in fiscal 2016.
– See more at: View Source#sthash.aXes4PST.dpuf