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TARIS Biomedical® Launches Second Phase 1b Clinical Trial of TAR-200 (GemRIS™) in Patients with Bladder Cancer

On August 10, 2016 TARIS Biomedical, a company developing powerful and targeted new treatments for millions of patients suffering from difficult-to-treat bladder diseases, reported the initiation of a Phase 1b clinical trial of TAR-200 (GemRIS, Gemcitabine Releasing Intravesical System) in patients with non-muscle-invasive bladder cancer (NMIBC) (Press release, TARIS Biomedical, AUG 10, 2016, View Source [SID:1234514500]). The study, which is being conducted in Europe, is the second Phase 1b trial of TAR-200 in bladder cancer. TARIS announced the initiation of a study in muscle-invasive bladder cancer (MIBC) in July 2016. TAR-200, a drug-device combination product utilizing the TARIS System, is designed to release gemcitabine continuously into the bladder over 7 days.

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"Non-muscle-invasive bladder cancer, which represents 70-75% of newly diagnosed cases, is a serious disease with a profound impact on the lives of patients. The current management of this cancer includes repeated surgical and pharmacological interventions, as well as lifelong monitoring. Despite these efforts, many patients are still at risk of recurrence and, in some cases, progression to MIBC," said Christopher J. Cutie, MD, Chief Medical Officer of TARIS. "TAR-200 may ultimately offer a unique non-surgical approach in the management of this disease."

"The initiation of a second study of TAR-200 is another substantial milestone for our organization," said Purnanand Sarma, Ph.D., President and Chief Executive Officer of TARIS. "If successful, these two studies are designed to demonstrate the potential utility of TAR-200 across the entire spectrum of bladder cancer. We are very excited to advance these programs into the clinic and look forward to the results."

About the TAR-200 Phase 1b Trial
The Phase 1b open-label study will assess whether continuous, local exposure to gemcitabine using TAR-200 is safe and tolerable in patients with intermediate risk NMIBC. The study will also assess the preliminary efficacy and pharmacokinetics in this patient population. The study will be conducted at multiple sites in Europe and expects to enroll up to 30 patients after the diagnosis of NMIBC and before transurethral resection of bladder tumors (TURBT).

About TAR-200
TAR-200 (GemRIS) is TARIS’ first product candidate in bladder cancer. TAR-200 is a drug-device combination product designed to release gemcitabine continuously into the bladder over 7 days. Gemcitabine is commonly used to treat multiple cancers alone and in combination with other chemotherapeutic drugs.1 TARIS believes TAR-200 has the potential to set a new standard of care in bladder cancer, with enhanced efficacy and minimal systemic side effects compared to current approaches. TARIS is developing TAR-200 to address unmet needs in both muscle-invasive and non-muscle-invasive bladder cancer.

About Non-Muscle-Invasive Bladder Cancer
Bladder cancer affects roughly 2.7 million people worldwide, including nearly 600,000 in the United States.2 The National Cancer Institute estimates that there will be a total of nearly 77,000 new cases and 16,000 deaths due to this disease in 2016.3 When measured as a cumulative lifetime per patient cost, bladder cancer exceeds all other forms of cancer.4 The estimated U.S. national expenditure on bladder cancer was $4.3 billion in 2014. 5

Non-muscle-invasive bladder cancer (NMIBC) represents 70-75% of newly diagnosed cases. NMIBC tumors are confined to the innermost layers of the bladder wall, and have not progressed into the deeper muscle layer or beyond. These tumors are currently managed using local resection (transurethral resection of bladder tumors or TURBT) and local pharmacological intervention. While current treatments often eliminate the existing tumor(s), the disease frequently recurs, requiring lifelong monitoring and repeated intervention. Further, higher-risk tumors that recur or progress despite these therapies often require patients to undergo radical cystectomy (complete surgical removal of the bladder). Radical cystectomy is a major, life changing procedure, and many patients are medically unfit and/or unwilling to undergo this surgery.

Oncolytics Biotech® Inc. Reports Additional Data from Randomized Phase II Study of REOLYSIN® in Non-Small Cell Lung Cancer

On August 10, 2016 Oncolytics Biotech Inc. ("Oncolytics" or the "Company") (TSX:ONC) (OTCQX:ONCYF) (FRA:ONY) reported additional data from IND 211, a randomized, Phase II clinical study of REOLYSIN in patients with non-small cell lung cancer ("NSCLC") (Press release, Oncolytics Biotech, AUG 10, 2016, View Source [SID:1234514493]). The study enrolled patients with both non-squamous (adenocarcinoma) and squamous cell histology. Those with adenocarcinoma (n=75) were treated with REOLYSIN in combination with pemetrexed in the test arm versus pemetrexed alone in the control arm. Those with squamous cell histology (n=76) were treated with REOLYSIN in combination with docetaxel in the test arm versus docetaxel alone in the control arm. The study’s primary objective was progression free survival ("PFS"). Its secondary objectives included overall survival ("OS"), safety, and measurement of biomarkers that may be predictive of response.

Results in Patients with Adenocarcinoma by Patient Gender
An analysis was performed of survival outcomes for patients with adenocarcinoma by gender. The PFS was statistically significantly better for female patients in the test arm (n=20) than for those in the control arm (n=16); median PFS was 5.39 months compared with 3.02 months, respectively (p=0.0201) (Figure A). The evolving OS showed a strong trend towards survival benefit for female patients in the test arm (n=20, six of whom remained alive at the time of the analysis) over those in the control arm (n=16, three of whom remained alive at the time of the analysis); median OS was 10.68 months compared with 7.59 months, respectively (p=0.145) (Figure B). By contrast, no PFS or OS benefit was noted for the male patients with adenocarcinoma.

"We are excited to see a statistically significant improvement in progression free survival for female patients with adenocarcinoma of the lung," said Dr. Brad Thompson, President and CEO of Oncolytics. "There is a significant unmet need for new therapies for non-small cell lung cancer patients."

Results in Patients with Adenocarcinoma by Patient Genetic Status
All patients were tested for biomarkers including those that are associated with the replication of the reovirus (namely, EGFR, Hras, Kras, Nras, Braf and/or p53 mutations) (the "target biomarkers"). Patients treated with REOLYSIN with one or more target biomarkers had a greater PFS (p=0.039) and OS (p=0.031) than patients treated with REOLYSIN without any of these biomarkers. The presence of these biomarkers may account, at least in part, for the difference between the survival outcomes for male and female patients; target biomarkers were present in a higher proportion of the female patients in the study than the male patients (66.7% versus 43.6%). As a result, pre-screening for target biomarkers in patients with adenocarcinoma of the lung is warranted.

Results in Patients with Squamous Cell Histology
The overall OS for patients with squamous cell histology continues to evolve. Target biomarkers were present in a smaller proportion of the overall patients with squamous cell histology (34.2% versus 54.7% of those with adenocarcinoma); therefore a larger patient population would be required to make statistical conclusions about the role of biomarkers in predicting response.

Next Steps
Based on the findings reported from IND 211, the Company intends to include preselection of patients using genetic screening in future study protocols.

About IND 211
IND 211 is an open-label, randomized, non-blinded two sided (adenocarcinoma and squamous cell carcinoma) Phase II study of intravenously administered REOLYSIN in patients with advanced or metastatic non-small cell lung cancer. Patients with squamous cell histology were treated with either REOLYSIN given in combination with docetaxel (test arm) or docetaxel alone (control arm). Patients with adenocarcinoma were treated with either REOLYSIN given in combination with pemetrexed (test arm) versus pemetrexed alone (control arm). After a patient safety run-in, a total of approximately 150 response-evaluable patients were enrolled. Preliminary data from this study were reported in May 2016. The study was sponsored by the Canadian Cancer Trials Group ("CCTG") at Queen’s University in Kingston, Ontario, formerly known as the National Cancer Institute of Canada ("NCIC") Clinical Trials Group.

About Non-Small Cell Lung Cancer
The American Cancer Society ("ACS") estimates that approximately 224,390 Americans will be diagnosed with lung cancer in 2016 and that 158,080 of them will die from the disease. Approximately 80% to 85% of lung cancer cases are non-small cell lung cancer. The ACS identifies multiple subtypes of non-small cell lung cancer based on the types of cells where they originate – adenocarcinoma accounts for about 40% of lung cancers and occurs more frequently in women than men; squamous cell carcinoma accounts for 25% to 30% of lung cancers; and large cell carcinoma accounts for 10% to 15% of lung cancers.

10-Q/A [Amend] – Quarterly report [Sections 13 or 15(d)]

(Filing, Q2, Mannkind, 2016, AUG 10, 2016, View Source [SID:1234514491])

Heron Therapeutics Announces U.S. FDA Approval of SUSTOL® (granisetron) Extended-Release Injection for the Prevention of Chemotherapy-Induced Nausea and Vomiting

On August 10, 2016 Heron Therapeutics, Inc. (NASDAQ:HRTX), reported that the U.S. Food and Drug Administration (FDA) has approved SUSTOL (granisetron) extended-release injection (Press release, Heron Therapeutics, AUG 10, 2016, View Source [SID:1234514460]). SUSTOL is a serotonin-3 (5-HT3) receptor antagonist indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens (Press release, Heron Therapeutics, AUG 10, 2016, View Source [SID:1234514460]).

SUSTOL is an extended-release, injectable 5-HT3 receptor antagonist that utilizes Heron’s Biochronomer polymer-based drug delivery technology to maintain therapeutic levels of granisetron for ≥5 days, covering both the acute and delayed phases of chemotherapy-induced nausea and vomiting (CINV).

"Despite advances in the management of CINV, up to half of patients receiving chemotherapy can still experience CINV, with delayed CINV being particularly challenging to control," commented Ralph V. Boccia, MD, FACP, Medical Director, Center for Cancer and Blood Disorders. "In our experience, other 5-HT3 receptor antagonists, including palonosetron, are generally effective for 48 hours or less. SUSTOL, due to its extended-release profile, represents a novel option that can protect patients from CINV for a full 5 days."

The SUSTOL global Phase 3 development program was comprised of two, large, guideline-based clinical trials that evaluated SUSTOL’s efficacy and safety in more than 2,000 patients with cancer. SUSTOL’s efficacy in preventing nausea and vomiting was evaluated in both the acute phase (day 1 following chemotherapy) and the delayed phase (days 2-5 following chemotherapy).
"The SUSTOL clinical trial populations and results are highly representative of cancer patients in our real-world clinical practice," said Jeffrey Vacirca, MD, FACP, Chief Executive Officer and Director of Clinical Research, North Shore Hematology Oncology Associates and Vice President, Community Oncology Alliance. "Use of MEC regimens is widespread, and AC-based regimens are among the most commonly prescribed highly emetogenic chemotherapy regimens. The most significant challenge for my breast cancer patients receiving AC is chemotherapy-induced nausea and vomiting. SUSTOL represents a better option to manage this devastating side effect of therapy."

"We would like to thank the investigators, caregivers and most of all the patients who have helped us to achieve this important milestone," commented Barry D. Quart, PharmD, Chief Executive Officer of Heron Therapeutics. "In addition to bringing an important product to patients, we are extremely pleased to have obtained the first approval of a product utilizing Heron’s Biochronomer polymer-based drug delivery technology."

"The approval of SUSTOL is a major step in Heron’s evolution into a fully-integrated biopharmaceutical company with both development and commercial capabilities," said Robert H. Rosen, President of Heron Therapeutics. "Our focus now turns to ensuring patients have access to this important therapy. We look forward to collaborating with the oncology community to make SUSTOL available in the fourth quarter of this year."

Lilly Provides Update on MONARCH 2 Phase 3 Trial of Abemaciclib

On August 10, 2016 Eli Lilly and Company (NYSE: LLY) reported that following a pre-planned interim analysis for MONARCH 2, an independent Data Monitoring Committee (DMC) provided the recommendation to continue the study without modification as the interim efficacy criteria were not met (Press release, Eli Lilly, AUG 10, 2016, View Source [SID:1234514459]). The MONARCH 2, Phase 3 trial compares abemaciclib plus fulvestrant* versus placebo with fulvestrant in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer.

"We had stringent criteria set for this interim analysis and we look forward to receiving the final MONARCH 2 results in the first half of 2017," said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. "We remain optimistic that treatment with abemaciclib, in combination with fulvestrant could offer improved outcomes for patients."

The Phase 3, double-blind study, designed to evaluate the safety and efficacy of abemaciclib in combination with fulvestrant, was conducted across 142 sites worldwide. The intent-to-treat population of 669 patients was randomized to receive abemaciclib or placebo orally every 12 hours on a continuous dosing schedule, given in combination with fulvestrant at the approved dose and schedule, until disease progression. Patients enrolled in the study had experienced disease progression on or within 12 months of receiving endocrine treatment in the neoadjuvant or adjuvant setting or while receiving first-line endocrine therapy for metastatic disease. Patients who had received chemotherapy in the metastatic setting were not eligible for the study. The primary endpoint for MONARCH 2 is progression-free survival (PFS).

The trial will continue into the first half of 2017 and will include a final analysis of PFS, overall survival and safety data.

Lilly will await further data and continue to work with the FDA to inform its submission plan for single-agent abemaciclib, based on the MONARCH 1 study. This Phase 2 study evaluated the single-agent activity and safety of abemaciclib in patients with refractory metastatic breast cancer, whose disease had progressed following multiple prior treatments, including chemotherapy.

Along with MONARCH 1 and MONARCH 2, Lilly currently has three additional MONARCH trials evaluating abemaciclib in breast cancer. MONARCH 3 is a Phase 3 trial of abemaciclib in combination with a nonsteroidal aromatase inhibitor in patients with HR+, HER2- locoregionally recurrent or metastatic breast cancer. Additionally, there are two Phase 2 MONARCH trials: neoMONARCH, which is evaluating abemaciclib in combination with a nonsteroidal aromatase inhibitor in the neoadjuvant setting, and monarcHER, which is evaluating abemaciclib plus trastuzumab (with or without fulvestrant) in women with HR+, HER2+ locally advanced or metastatic breast cancer.

For more information on additional abemaciclib trials, a complete listing can be found on ClinicalTrials.gov.

About Metastatic Breast Cancer
Breast cancer is the most common cancer in women worldwide with nearly 1.7 million new cases diagnosed in 2012.1 In the U.S. this year, approximately 246,660 new cases of invasive breast cancer will be diagnosed and about 40,450 people will die from breast cancer.2 Of all early stage breast cancer cases diagnosed in the U.S., approximately 30 percent will become metastatic, spreading to other parts of the body. In addition, an estimated six to 10 percent of all new breast cancer cases are initially diagnosed as being stage IV, or metastatic.3 Metastatic breast cancer is considered incurable, but is generally treatable.

About Abemaciclib
Abemaciclib (LY2835219) is an investigational, oral cell cycle inhibitor, designed to block the growth of cancer cells by specifically inhibiting cyclin-dependent kinases, CDK 4 and CDK 6. In many cancers, uncontrolled cell growth arises from a loss of cell cycle regulation due to increased signaling from CDK 4 and CDK 6. Abemaciclib inhibits both CDK 4 and CDK 6, and was shown in cell-free enzymatic assays to be most active against Cyclin D 1 and CDK 4.

In 2015, the U.S. Food and Drug Administration granted abemaciclib Breakthrough Therapy Designation based on data from the breast cancer cohort expansion of the company’s Phase 1 trial, JPBA, which studied the efficacy and safety of abemaciclib in women with advanced or metastatic breast cancer. In addition to its current MONARCH clinical trials evaluating abemaciclib in breast cancer, a Phase 3 trial of abemaciclib in lung cancer is also underway.