On June 6, 2016 Array BioPharma (Nasdaq: ARRY) reported full results at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Abstract No. 9500) from the pivotal Phase 3 NEMO (NRAS MELANOMA AND MEK INHBITOR) trial of binimetinib (Press release, Array BioPharma, JUN 6, 2016, View Source;p=RssLanding&cat=news&id=2175437 [SID:1234513066]). The study found binimetinib significantly extended median progression-free survival (PFS), the study’s primary endpoint, at 2.8 months, as compared with 1.5 months observed with dacarbazine [hazard ratio (HR)=0.62 (95% CI 0.47-0.80), p<0.001] – the first trial to ever meet a PFS endpoint in patients with advanced NRAS-mutant melanoma. In the pre-specified subset of patients who received prior treatment with immunotherapy, including ipilimumab, nivolumab or pembrolizumab, patients who received binimetinib experienced 5.5 months of median PFS (95% CI, 2.8–7.6), compared with 1.6 months for those receiving treatment with dacarbazine (95% CI, 1.5–2.8).

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Array BioPharma. (PRNewsFoto/Array BioPharma Inc.)
"The NEMO findings are promising and suggest binimetinib may provide a new treatment option for the thousands of patients who are diagnosed with NRAS-mutant melanoma," said lead study investigator Reinhard Dummer, M.D., Professor, Dept. of Dermatology, University of Zurich Hospital. "Particularly compelling are the results in the pre-specified sub-group of patients who had received prior treatment with immunotherapy, which is now recognized as the standard of care for first-line treatment in this patient population."

In addition to improving PFS, binimetinib also demonstrated significant improvement in overall response rate (ORR) and disease control rate (DCR). While there was no statistically significant difference demonstrated in overall survival, the median overall survival (mOS) favored the binimetinib arm.

Confirmed ORR was 15 percent (95% CI, 11-20 percent) in patients receiving binimetinib vs. 7 percent (95% CI, 3-13 percent) in patients receiving dacarbazine.
DCR for patients receiving binimetinib was 58 percent (95% CI, 52-64 percent) vs. 25 percent (95% CI, 18-33 percent) for patients receiving dacarbazine.
mOS was estimated at 11.0 months in patients receiving binimetinib vs. 10.1 months for patients treated with dacarbazine [(HR) = 1.0 (95% CI 0.75-1.33), p=0.499].
"NRAS-mutant melanoma impacts one out of five advanced melanoma patients, yet there are currently no treatment options indicated specifically for these patients," said study investigator Keith T. Flaherty, M.D., Director of the Termeer Center for Targeted Therapy, Massachusetts General Hospital and Professor of Medicine, Harvard Medical School. "There remains a need for additional effective treatments for patients with NRAS–mutant disease. Binimetinib may provide another important treatment option for this patient population."

Binimetinib was generally well-tolerated and the adverse events (AEs) reported were consistent with previous results in NRAS-mutant melanoma patients. Grade 3/4 AEs reported in greater than or equal to 5 percent of patients receiving binimetinib included increased creatine phosphokinase (CPK) and hypertension.

"The NEMO trial results demonstrate the potential of binimetinib to help slow disease progression in this patient population, an often overlooked subset without treatment options beyond immunotherapy," explained Victor Sandor, M.D., Chief Medical Officer, Array BioPharma. "Based on the strength of these data, we plan to submit our regulatory filing for binimetinib in NRAS-mutant melanoma later this month."

About NEMO
The NEMO trial, (NCT01763164), is an international, randomized Phase 3 study in patients with advanced NRAS-mutant melanoma. 402 patients were randomized 2:1 to receive continuous 45 mg BID binimetinib or 1,000 mg/m2 dacarbazine dosed every three weeks. Prior immunotherapy treatment was allowed. The primary endpoint of the study is progression-free survival, and overall survival is a key secondary endpoint. Patients underwent radiographic assessment of disease status every six weeks, and assessment of progression was determined by blinded central review. Over 100 sites across North America, Europe, South America, Asia and Australia participated in the study.

About NRAS-Mutant Melanoma
Melanoma is the fifth most common cancer among men and the seventh most common cancer among women in the United States, with more than 76,000 new cases and nearly 10,000 deaths from the disease projected in 2016. 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 Binimetinib
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, which targets key enzymes in this pathway.

Binimetinib is currently being studied in Phase 3 trials in advanced cancer patients, including the COLUMBUS trial studying encorafenib in combination with binimetinib in patients with BRAF-mutant melanoma and the recently initiated BEACON trial that will study encorafenib in combination with binimetinib and cetuximab in patients with BRAF V600E-mutant colorectal cancer. Array projects COLUMBUS top-line results availability during the third quarter of 2016.

On June 06, 2016 Atara Biotherapeutics, Inc. (Nasdaq:ATRA), a biopharmaceutical company focused on developing meaningful therapies for patients with severe and life threatening diseases that have been underserved by scientific innovation, reported that its collaborating investigators at Memorial Sloan Kettering Cancer Center (MSK) reported clinical results for Atara’s allogeneic Epstein-Barr Virus Cytotoxic T-Lymphocyte (EBV-CTL) product candidate (Press release, Atara Biotherapeutics, JUN 6, 2016, View Source [SID:1234513088]). Data were presented from an on-going Phase 2 clinical trial, which enrolled a heterogeneous group of EBV associated malignancies including NPC and post-transplant lymphoproliferative disorders, at an oral presentation at the ASCO (Free ASCO Whitepaper) 2016 Annual Meeting. This data included safety and efficacy of EBV-CTL in the treatment of 14 patients with recurrent metastatic nasopharyngeal carcinoma (NPC). EBV-associated NPC accounts for approximately 6,000 cases annually in the US and EU combined and approximately 80,000 cases worldwide. Historical median survival rates range from five to eleven months for patients with metastatic disease.

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Dr. Susan Prockop, M.D., and colleagues reported the following data:

A 21% objective response rate in NPC patients, including one complete response, and two partial responses.
11 of the 14 NPC patients were alive with median 18-month follow-up.
EBV-CTLs expanded after administration to immunocompetent NPC patients without concomitant lymphodepleting chemotherapy.
Of the 126 patients enrolled across all indications, there were two grade 4 and seven grade 3 possibly related serious adverse events.
"We are pleased that this study has demonstrated the potential therapeutic benefit of an allogeneic therapy for patients with solid tumors," commented Chris Haqq M.D., Ph.D., Chief Medical Officer of Atara Bio. "We look forward to developing this product candidate as both a single agent and in combination with other therapies in NPC and other indications. In addition, we will be commencing our two upcoming pivotal trials in patients with rituximab refractory EBV Post-Transplant Lymphoproliferative Disorder (EBV-PTLD) after solid organ transplant (SOT) and hematopoietic stem cell transplant (HCT) later this year."

About EBV-CTL

T-cells are a critical component of the body’s immune system and can be harnessed to counteract viral infections and some cancers. By focusing the T-cells on specific proteins involved in cancers and infections, the power of the immune system can be employed to combat these diseases. Atara Bio’s EBV-CTL utilizes a technology in which T cells are collected from the blood of third-party donors and then exposed to EBV antigens. The resulting activated T cells are then expanded, characterized, and stored for future therapeutic use in an appropriate partially human leukocyte antigen, or HLA, matched patient, providing an "off-the-shelf", allogeneic, cellular therapeutic option for patients. EBV-CTLs are designed to find cancer cells expressing EBV and kill them. Phase 2 clinical results from trials conducted at MSK have been reported in multiple peer-reviewed forums. Atara Bio plans to commence two pivotal clinical trials of EBV-CTL for rituximab-refractory EBV Post-Transplant Lymphoproliferative Disorder (EBV-PTLD) following hematopoietic cell transplant (HCT), as well as solid organ transplant (SOT), towards the end of 2016.

On June 6, 2016 Heat Biologics, Inc. (Nasdaq:HTBX), an immuno-oncology company developing novel therapies that activate a patient’s immune system against cancer, reported that it presented a poster entitled "Broadening response rates to PD-1 therapy in advanced lung adenocarcinoma: Viagenpumatucel-L (HS-110) in combination with nivolumab in the ongoing DURGA trial" (Abstract #TPS9102) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Heat Biologics, JUN 6, 2016, View Source [SID:1234513020]). The poster was accepted within the Trials in Progress category and as such, reviewed the design and endpoints for the ongoing Phase 1b study of HS-110 in combination with anti-PD-1 checkpoint inhibitor, nivolumab, for the treatment of non-small cell lung cancer (NSCLC). Eight patients are currently enrolled.

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Recent study findings, not presented at ASCO (Free ASCO Whitepaper), suggest that the addition of HS-110 to nivolumab does not significantly alter the nivolumab safety profile to-date. In addition, case studies of three trial patients (one non-responder and two responders) have been characterized. While all three patients showed a decrease in immune cell PD-1 expression, which is consistent with nivolumab’s mechanism of action, both responders also showed a decrease in immunosuppressor cells, as well as increases in activated effector T cells in the peripheral blood. Furthermore, the two responders showed an increase in CD8+ T cells in biopsy samples after treatment with the HS-110/nivolumab combination. ELISPOT analysis of patient blood samples demonstrated induction of antigen-specific immune responses to both total vaccine antigen and individual shared tumor antigens in both responding patients, but not the clinical non-responder. Finally, these responding patients also had low-grade injection site reactions in addition to rash, which the non-responder did not, suggesting their clinical and immune responses may be attributed to the HS-110 vaccine.

These data are included in the updated corporate presentation which is available on Heat’s corporate website at www.heatbio.com. As previously announced, full topline data on all eight patients is expected to be presented in the fourth quarter, including all primary and secondary endpoints.

"In these early data, we observed a correlation between patients’ clinical outcomes and their immunological responses, which we believe indicates that tumor response may be a result of increased immunological activity," said Melissa Price, Ph.D., Heat’s VP of Product Development. "Additionally, the two responders qualitatively converted from low to high tumor infiltrating lymphocytes (TILS), which is consistent with data previously reported from our bladder cancer study. This finding supports our hypothesis that patients with low levels of TILs, who typically do not respond well to single-agent checkpoint inhibitors, may respond to a combination with our ImPACT vaccine."

On June 6, 2016 Bio-Path Holdings, Inc., (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer and autoimmune drugs, reported that data from the Phase I study of BP1001 (Liposomal Grb2 Antisense) as a treatment for acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) and the safety segment of the Phase II combination therapy of BP1001 and low-dose cytarabine (LDAC) as a treatment for advanced AML were presented by Dr. Maro Ohanian, Assistant Professor at the University of Texas MD Anderson Cancer Center, during a poster presentation at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in a poster titled, "Phase I Study of BP1001 (Liposomal Grb2 Antisense) in Patients with Hematologic Malignancies (Filing, 8-K, Bio-Path Holdings, JUN 6, 2016, View Source [SID:1234513067])."

"While a small dataset, we are still very excited by these robust data showing that five of six evaluable patients demonstrated activity, especially for these refractory and resistant patients. We are also encouraged by the lack of toxicity as our Phase II efficacy segment will be in de novo fragile patients, for whom the drug side effect profile is particularly important," stated Peter H. Neilson, Chief Executive Officer of Bio-Path Holdings. "In addition, we were very pleased with BP1001’s pharmacokinetics, particularly its 30-hour half-life. The final analysis of these data, along with the demonstrated reductions in bone marrow blasts, suggests that 60 mg/m2 is the appropriate dose going forward."

The Phase I study of BP1001 comprised Cohorts 1 through 6 of the dose-finding monotherapy at doses up to 90 mg/m2 in refractory/relapsed leukemia patients. The safety segment of the Phase II study evaluated the toxicity of BP1001 in Cohorts 7 and 8 in doses of 60 mg/m2 and 90 mg/m2, combined with LDAC chemotherapy in refractory/relapsed patients with advanced AML.

Data from the safety segment of the Phase II combination therapy of BP1001 and LDAC showed no dose limiting toxicities. Of the six evaluable patients, four patients completed more than two cycles of treatment, three patients achieved complete remission and two patients achieved partial remission. BP1001 levels decreased bi-exponentially in plasma and the pharmacokinetics of BP1001 demonstrated a half-life at 60 mg/m2 of 30 hours.

As previously reported, data from the Phase I study demonstrated that BP1001 was well tolerated in refractory/relapsed leukemia patients at doses up to 90 mg/m2 with no drug related adverse events. It also decreased target Grb2 expression by an average of 50% in the 21 evaluable patients on BP1001 monotherapy. Of these patients in the Phase I study, seven patients completed more than two cycles of treatment, 10 patients had more than a 50% reduction in peripheral or bone marrow blasts and six patients had transient decline in blasts (n=3) and/or stable disease (n=3), with two patients experiencing transient improvement in leukemia cutis lesions.

About BP1001

BP1001 is a neutral-charge, liposome-incorporated antisense drug substance designed to inhibit Grb2 protein expression. The protein Grb2 is essential to cancer cell signaling because it is utilized by oncogenic tyrosine kinases to induce cancer progression. Suppressing the function or expression of Grb2 should interrupt its vital signaling function and have a therapeutic application in cancer.

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On June 6, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) reported new data informed by comprehensive genomic profiling (CGP) using FoundationOne Heme demonstrating the diverse and distinct genomic landscape of acute myeloid leukemia (AML) in children versus adults (Press release, Foundation Medicine, JUN 6, 2016, View Source [SID:1234513044]). Foundation Medicine conducted comprehensive genomic profiling of tumor samples from 558 patients with AML, including 104 pediatric and 454 adult patients, and identified age-associated genomic alterations in a subset of patients that could influence and personalize treatment and inform the selection of approved targeted therapies or access to novel therapies available in clinical trials.

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In collaboration with the Children’s Oncology Group AML Disease Committee, a clinical trials group supported by the National Cancer Institute (NCI), cases with known cytogenetic and molecular aberrations underwent CGP with FoundationOne Heme. The results demonstrated 100% concordance between FoundationOne Heme and conventional biomarker analysis across the various cytogenetic hallmarks of AML, including changes to inv(16) and t(8;21), as well as DNA mutations including FLT3/ITD, NPM1, and CEBPA. Importantly, FoundationOne Heme identified multiple additional mutations, such as structural alterations and copy number variations, including alterations that have therapeutic significance. These results suggest the potential clinical benefit of FoundationOne Heme in AML as compared to single gene or hotspot-based clinical testing, and underscore FoundationOne Heme’s unique capability to enhance risk stratification and identify molecular targets for therapeutic intervention.

The data showed a clear age-associated profile with distinct genomic make-up in pediatric versus adult patients. Novel transcripts such as NSD1-NUP98, KDM5A-NUP98 and CBFA2T3-GLIS2 were identified in 21 patients, 16 of whom were children. Fusions were markedly enriched in pediatric patients, while mutations in epigenetic modifiers occurred almost exclusively in adults, including DNMT3A (22 percent), IDH1/2 (21 percent) and TET2 (15 percent). Mutations in ASXL1 (21 percent), SRSF2 (14 percent) and BCOR (9 percent) were also prevalent in adults, but rare in children (0-6%).

"Like many blood cancers, AML is characterized by recurring genomic alterations that often provide information about disease progression and outcome, making comprehensive genomic profiling incredibly important to informing diagnosis and therapeutic decisions," said Vincent Miller, M.D., chief medical officer, Foundation Medicine. "Recognizing that there are fundamental differences between the genomic alterations in pediatric versus adult AML patients will ultimately arm clinicians with additional information to better understand each patient’s disease and guide therapeutic regimens best suited to a particular age group. We believe these data further support integration of FoundationOne Heme into oncology clinical practice."

The findings were presented in a poster titled, "Distinct Age-Associated Genomic Profiles Identified in Acute Myeloid Leukemia (AML) Using FoundationOne Heme," by Katherine Tarlock, M.D., pediatric hematology-oncology faculty at Seattle Children’s Hospital, and a member of the Children’s Oncology Group AML Committee. The data were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2016 taking place June 3-7 in Chicago.

FoundationOne Heme, an integrated DNA/RNA platform using targeted hybrid-capture next-generation sequencing, is a comprehensive genomic profile developed to detect all types of genomic alterations with therapeutic relevance, including single-nucleotide substitutions, insertions and deletions, copy number alterations and rearrangements, which are not fully evaluated using conventional diagnostic assays. FoundationOne Heme simultaneously detects all classes of genomic alterations in the DNA of 405 cancer-related genes and employs RNA sequencing across 265 genes to capture a broad range of gene fusions, a type of alteration that is a common driver of hematologic cancers. It is designed to provide physicians with clinically actionable information to guide treatment options for patients based on the genomic profile of their cancer.

About Foundation Medicine

Foundation Medicine (NASDAQ:FMI) is a molecular information company dedicated to a transformation in cancer care in which treatment is informed by a deep understanding of the genomic changes that contribute to each patient’s unique cancer. The company offers a full suite of comprehensive genomic profiling assays to identify the molecular alterations in a patient’s cancer and match them with relevant targeted therapies, immunotherapies and clinical trials. Foundation Medicine’s molecular information platform aims to improve day-to-day care for patients by serving the needs of clinicians, academic researchers and drug developers to help advance the science of molecular medicine in cancer. For more information, please visit View Source or follow Foundation Medicine on Twitter (@FoundationATCG).