On April 14, 2016-Presage Biosciences, an oncology company that has established a novel drug development approach to assess drug combinations directly in patient tumors, reported that is has entered into a multi-year extension of its November 2014 research alliance with Takeda Pharmaceuticals Company Limited (TSE:4502) (Press release, Presage Biosciences, APR 14, 2016, View Source [SID:1234510837]).

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The agreement provides Takeda access to Presage’s proprietary CIVO technology platform to enable identification of novel oncology drug combinations in solid tumors. Under the agreement, Presage and Takeda will screen a broad array of drug combinations and preclinical models to discover novel combinations and generate data to support clinical decision-making on Takeda’s pipeline agents. The agreement includes development and regulatory milestones related to identification of successful novel drug combinations.

"We are pleased to extend our collaboration with Presage and utilize their technology platform to more rapidly understand the impact of drug combinations directly on tumors," said Christopher Claiborne, Ph.D., Head of the Oncology Drug Discovery Unit at Takeda. "Takeda prides itself on creating novel medicines for patients, and having a committed partner like Presage enables us to continue fulfilling our mission of aspiring to cure cancer."

"It is deeply rewarding to continue our collaboration with Takeda," said Richard Klinghoffer, Chief Scientific Officer of Presage. "Together, the teams at Presage and Takeda are employing the unique potential of Presage’s CIVO arrayed microinjection technology to identify novel drug combinations that will hopefully improve the lives of patients with cancer."

CIVO technology is currently being used preclinically to identify effective combinations of drugs. By assessing several combinations in a single living tumor, the CIVO platform is able to characterize and directly compare the influence of multiple biophysical factors such as immune infiltrate, stromal barrier and hypoxia on the tumor response.

On April 14, 2016 Leica Biosystems and Merrimack Pharmaceuticals (NASDAQ: MACK) reported a strategic partnership to develop companion diagnostic assays to aid in identification of patients who might best respond to current and future oncology therapies developed by Merrimack (Press release, Merrimack, APR 14, 2016, View Source [SID:1234510833]). The assays will be designed using Advanced Cell Diagnostics’ (ACD’s) RNAscope technology and will be processed on Leica Biosystems’ BOND clinical advanced staining systems.

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The initial focus of this partnership will be the development of a companion diagnostic assay for Merrimack’s seribantumab, or MM-121, an investigational therapy. Seribantumab is a fully human, monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin (HRG). Heregulin-driven ErbB3 signaling identifies a unique, more difficult to treat cancer phenotype characterized by increased tumor growth and increased resistance to targeted, cytotoxic and anti-endocrine therapies. Seribantumab is being investigated primarily in combination settings, to block HRG activated ErbB3 signaling in order to enhance the anti-tumor effect of the combination therapy partner.

"We are pleased to be working with Merrimack on cancer therapies with the BOND platform," added Matthias Weber MD, President of Leica Biosystems. "The partnership utilizing RNAscope technology is an example of Leica Biosystems paving the way for in situ RNA detection in personalized medicine. The ease of use and high quality staining delivered by BOND systems makes them ideal platforms on which to deploy these very informative tests."

"Our increased understanding of cancer cell biology is driving the need for companion diagnostic tests to ensure the right patients get the right therapies," said Jason Baum, Director, Companion Diagnostics at Merrimack. "The use of RNAscope technology on Leica Biosystems’ automated staining platforms will allow us to detect HRG with high sensitivity and specificity, helping to identify the patients most likely to benefit from seribantumab treatment. HRG is the cognate ligand of the ErbB3 receptor and a powerful driver of cell survival signaling. HRG tumor expression has been implicated in defining a distinct, difficult to treat cancer phenotype that is found across multiple solid tumors at a prevalence rate of approximately 30-50% in major indications. We are pleased to have partnered with Leica Biosystems on this project."

Leica Biosystems’ work program will be led from their Companion Diagnostics Research and Development site in Danvers, Greater Boston, Massachusetts, with kit manufacturing occurring in Newcastle.

On April 14, 2016 Oncolytics Biotech Inc. (TSX: ONC) (OTCQX: ONCYF) (FRA: ONY) ("Oncolytics" or the "Company") reported updated results for a randomized Phase 2 clinical trial of its lead product, REOLYSIN, in combination with carboplatin and paclitaxel in patients with pancreatic cancer (NCI-8601) (Filing, 6-K, Oncolytics Biotech, APR 14, 2016, View Source [SID:1234510816]).

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The study is being sponsored by the U.S. National Cancer Institute ("NCI"). The update is based on data collected up to January 19, 2016 from the NCI and updates information from previous disclosures by the principal investigator.

Update Highlights

Overall survival ("OS") of control, test, crossover, and combined test and crossover arms

Arm Median OS
(months) 1-year OS
(%) 2-year OS
(%) 3-year OS
(%)
Control (n = 20) 6.57 25.0 0 0
Test (n = 36) 7.33 29.6 17.7 8.87
Crossover (n = 16) 10.97 25.0 12.5 6.25
Combined Test and
Crossover
(n = 52) 8.73 28.1 16.0 8.02
Source: NCI Clinical Trial Summary: Response Information Report

The Company performed an intent-to-treat analysis of overall survival on patients with confirmed treatment regimes, as assessed by the percentage of patients surviving for two years. The analysis showed a statistically significantly higher percentage of patients surviving two years in the test arm versus the control arm (p = 0.001), the crossover arm versus the control arm (p = 0.03) and the test plus crossover arms versus the control arm (p = 0.0004). At the time of the data cut off (January 19, 2016), there were five survivors on study in the test arm, and one survivor on study in the crossover arm. As a result, the two- and three-year survival for the arms may continue to evolve.

"These data clearly illustrate that patients receiving REOLYSIN, whether in the test arm or crossing over after progressing in the control arm, received a benefit in longer-term overall survival," said Dr. Brad Thompson. "The overall survival findings in this study build on what we saw in our REO 017 study, where the combination of REOLYSIN and gemcitabine, also produced a clear longer-term overall survival benefit, despite having limited impact on progression free survival. This is characteristic of clinical studies where the immune system affects patient outcomes. Based on these combined results, we are currently enrolling pancreatic cancer patients in a study incorporating REOLYSIN plus the checkpoint inhibitor KEYTRUDA to determine the effect of the immune system on patient outcomes."

This was one in a series of randomized Phase 2 studies with REOLYSIN that were designed and sponsored by third parties to test their specific hypotheses, and the Company intends to use these findings to further advance its own clinical program.

Study Design Summary
The study was an open-label, multi-institution, two-arm Phase 2 randomized study of patients with metastatic pancreatic cancer. Patients were randomized to receive either carboplatin, paclitaxel and REOLYSIN (test arm) or carboplatin and paclitaxel alone (control arm). Patients in both arms received treatment every three weeks (21-day cycles) and standard intravenous doses of paclitaxel and carboplatin on day one only. In the test arm, patients also received intravenous REOLYSIN at a dose of 3×1010 TCID50 on days one through five. Tumor response was assessed by computed tomography (CT) scan and conducted every eight weeks. Patients who progressed on carboplatin and paclitaxel (control arm) had REOLYSIN added (crossover arm). If patients experienced significant toxicity related to carboplatin and/or paclitaxel, they could continue with single agent REOLYSIN.

The primary endpoint of the trial is to assess improvement in progression free survival with REOLYSIN, carboplatin and paclitaxel relative to carboplatin and paclitaxel alone in patients with metastatic pancreatic cancer. Secondary endpoints include safety, overall response rate, overall survival, immune factors and to prospectively establish and validate the relationship between Ras mutations in tumor samples and response to REOLYSIN. For this analysis, the control arm is patients receiving carboplatin and paclitaxel alone, the test arm is patients receiving carboplatin, paclitaxel, and REOLYSIN, and the crossover arm is patients initially treated with carboplatin and paclitaxel alone, who progressed and subsequently had REOLYSIN added to their treatment regime.

About Oncolytics Biotech Inc.

On April 14, 2016 Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, reported that results from the NEfERT-T Phase II clinical trial of neratinib in ERBB2-positive metastatic breast cancer patients were published online in JAMA Oncology (Press release, Puma Biotechnology, APR 14, 2016, View Source [SID:1234510802]). The article, entitled "Neratinib Plus Paclitaxel vs. Trastuzumab Plus Paclitaxel in Previously Untreated Metastatic ERBB2-Positive Breast Cancer: The NEfERT-T Randomized Clinical Trial," appears in the April 14, 2016 online issue and will be published in a future print issue of the journal.

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The NEfERT-T trial is a randomized, two-arm Phase II trial of neratinib plus the anticancer drug paclitaxel versus trastuzumab (Herceptin) plus paclitaxel as a first-line treatment for ERBB2-positive (previously referred to as HER2-positive) locally recurrent or metastatic breast cancer. The trial enrolled 479 patients in 33 countries who had not received prior anticancer therapy for locally recurrent or metastatic disease. Patients were randomized to receive first-line treatment with either paclitaxel plus neratinib or paclitaxel plus trastuzumab. The primary endpoint of the trial was progression-free survival (PFS). The secondary endpoints of the study included objective response rate (ORR) and the incidence of central nervous system (CNS) metastases, including brain metastases.

The results of the trial demonstrated that the progression-free survival for the patients who received the combination of paclitaxel plus neratinib was 12.9 months and the progression-free survival for the patients who received the combination of paclitaxel plus trastuzumab was 12.9 months (hazard ratio 1.02, p=0.89). The objective response rate in the trial for the patients who received the combination of paclitaxel plus neratinib was 74.8% and the objective response rate for the patients who received the combination of paclitaxel plus trastuzumab was 77.6% (p=0.52).

With respect to the incidence of CNS metastases (e.g., brain metastases), treatment with the combination of paclitaxel plus neratinib resulted in a 52% reduction in the incidence of CNS metastases compared to the incidence of CNS metastases in patients who received the combination of paclitaxel plus trastuzumab. Symptomatic or progressive CNS recurrences occurred in 20 patients (8.3%) in the neratinib-paclitaxel group and 41 patients (17.3%) in the trastuzumab-paclitaxel group (relative risk 0.48, p=0.002). The estimated Kaplan-Meier 2-year incidence of CNS recurrences was 16.3% in the neratinib-paclitaxel group and 31.2% in the trastuzumab-paclitaxel group (hazard ratio 0.45, p=0.004). These results reflect a statistically significant difference between the two treatment arms.

"The NEfERT-T trial represents the first randomized trial with a HER2-targeted agent that has shown a statistically significant reduction in the incidence of CNS metastases," said Alan H. Auerbach, Chief Executive Officer and President. "We believe this provides a meaningful point of differentiation for neratinib in the treatment of HER2-positive breast cancer. We are pleased that JAMA Oncology has chosen to publish these results."