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ZIOPHARM Presents Data Demonstrating Activation of Anti-Tumor Immune Response Using Ad-RTS-hIL-12 in Patients with Advanced Breast Cancer

On October 10, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP) reported the presentation of preliminary data from the Company’s Phase 1b/2 study of Ad-RTS-hIL-12 + veledimex following standard chemotherapy for the treatment of patients with locally advanced or metastatic breast cancer (Press release, Ziopharm, OCT 10, 2016, View Source [SID:SID1234515715]). The poster presentation, titled "Phase 1b/2 study of intratumoral Ad-RTS-hIL-12+veledimex in patients with chemotherapy-responsive locally advanced or metastatic breast cancer," was presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress today in Copenhagen, Denmark.

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The study, which is being conducted at the Memorial Sloan Kettering Cancer Center in New York, is designed to examine the safety, tolerability and efficacy of Ad-RTS-hIL-12 immunotherapy in up to 40 women with locally advanced or metastatic breast cancer of all subtypes. Ad-RTS-hIL-12 + veledimex is a novel gene therapy which controls local expression of IL-12. The ability to regulate the production of IL-12 by modulating veledimex dosing is designed to improve its therapeutic index with standard of care.

Following entry into the trial, patients go on a chemotherapy holiday and enter an immunotherapy phase of treatment. A single cycle of Ad-RTS-hIL-12, along with the oral activator ligand veledimex, is given during the immunotherapy phase, with the goal of maintaining or improving pre-study response.

As of August 30, 2016, a total of nine patients were available for initial assessment. Results show that Ad-RTS-hIL-12 + 7 days of veledimex consistently elicited production of IL-12 which in turn produced IFNγ. It was notable that the intratumoral influx of CD8+ T cells and IFNγ were present six weeks after completion of veledimex consistent with the ability of Ad-RTS-hIL-12 to favorably impact the tumor environment over the long term. In two patients, Ad-RTS-hIL-12 + veledimex provided a meaningful drug holiday, with durable responses for 18 and 35 weeks. In all patients, disease control rate (DCR) was 44% at Week 6 and 22% at Week 12. Overall response rate (ORR), defined as achieving a partial response (PR) or better, was 11% at Week 12. Most toxicities promptly reversed upon discontinuation of veledimex, including cytokine release syndrome (grade 1-2 CRS), observed in six of nine patients. The higher than expected incidence of CRS was likely related to CYP-3A4 drug interactions with veledimex (80 mg) which resulted in enhanced peak cytokine expression.

"These data provide additional evidence that IL-12 expression and corresponding downstream signaling is activated using Ad-RTS-hIL-12 + veledimex, consistent with results observed in other studies and tumor types," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "Early results from this study are promising, providing further support and validation for our ongoing study of Ad-RTS-hIL-12 in glioblastoma, a program we anticipate moving into a pivotal trial."

ESMO Presentation Details

Title: Phase 1b/2 study of intratumoral Ad-RTS-hIL-12+veledimex in patients with chemotherapy-responsive locally advanced or metastatic breast cancer
Abstract Number: 280P
Date and Time: October 10, 2016, 1:00-2:00p CET
Location: Hall E

Peregrine Pharmaceuticals Reports Top-Line and Initial Biomarker Data from Phase III SUNRISE Trial of Bavituximab in Oral Presentation at European Society for Medical Oncology (ESMO) 2016 Congress

On October 10, 2016 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company committed to improving patient lives by manufacturing high quality products for biotechnology and pharmaceutical companies and advancing its proprietary R&D pipeline, reported that top-line data from the Phase III SUNRISE trial of bavituximab in patients with previously treated locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) were presented in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress (Press release, Peregrine Pharmaceuticals, OCT 10, 2016, View Source [SID:SID1234515714]). The presentation included interim efficacy and safety outcomes, as well as initial findings from the company’s ongoing biomarker analysis of samples collected during the study. The SUNRISE Phase III trial was discontinued earlier this year based on a pre-specified interim analysis although patient treatment and follow-up in the study were allowed to continue. The pre-planned biomarker analysis has been taking place as patient follow-up has continued and available results were evaluated as part of the recent top-line data analysis.

The study protocol pre-specified the collection of thousands of patient samples for exploratory analyses over a wide range of possible biomarkers, including pre-treatment levels of beta-2 glycoprotein-1 (β2GP1). Data presented at ESMO (Free ESMO Whitepaper) demonstrated that patients with pre-treatment β2GP1 levels between 200 and 240 (representing approximately 30% of randomized patients) achieved a statistically significant, 5.5-month improvement (13.2 months vs. 7.7 months) in median overall survival (OS) as compared to patients in the control group with the same range of β2GP1 levels [p = 0.049; hazard ratio (HR) = 0.67]. A similar trend was observed with pre-treatment β2GP1 levels ≥ 200 µg/mL (representing approximately 50% of randomized patients) with 11.9 months vs. 10.1 months median OS in favor of the bavituximab-containing group (p = 0.155; HR = 0.81). Taken together, this strongly suggests β2GP1 levels may be useful for identifying patients who are more likely to benefit from a bavituximab containing therapeutic regimen. Numerous additional biomarkers are currently being analyzed with the goal of developing a multi-marker signature that can potentially identify patients that are likely to receive significant clinical benefit from a bavituximab-containing therapeutic regimen.

Top-line results reported at ESMO (Free ESMO Whitepaper) today were based on a data cut-off after 70% (330/473) of the targeted OS events had been reached and demonstrated the addition of bavituximab to docetaxel did not result in improvement of the study’s primary endpoint of OS in the intent-to-treat population. Median OS for the bavituximab plus docetaxel group was 10.7 months as compared to 10.8 months for the placebo plus docetaxel control group (HR = 1.110; p = 0.382). Median progression free survival (PFS) for the bavituximab-containing group was 4.1 months compared to 3.9 months for the control group (HR = 0.97; p = 0.803). Objective response rates based on independent central review are currently 13% and 11% (p = 0.53) for the bavituximab-containing and control groups, respectively. Additionally, the safety profile of the combination of bavituximab with docetaxel was similar to placebo plus docetaxel.

"With every clinical trial we conduct, we are constantly reminded of the difficulty involved in treating patients with non-small cell lung cancer. This continues to prove to be a very challenging cancer to combat and the need for effective treatments remains high," David R. Spigel, MD, chief scientific officer and program director of Lung Cancer Research at the Sarah Cannon Research Institute and one of the lead investigators in the SUNRISE trial. "The findings with regard to β2GP1 that have been collected as part of the ongoing SUNRISE trial data analysis are interesting and support further investigation."

Peregrine intends to further evaluate the role of β2GP1 levels in response to bavituximab therapy in future clinical trials. The company has filed a new patent application directed to the use of this initial biomarker discovery. Additional patient sample testing and analysis is ongoing and may result in other biomarkers of importance.

"We would once again like to thank all of the patients, clinical investigators and scientists who participated in the SUNRISE trial and have made it possible for us to continue to collect and analyze a range of key data from the study. While we were disappointed with the trial being discontinued earlier in the year, we are excited by the fact that we are beginning to learn important information from the trial through the ongoing biomarker analysis program that will be critical in helping guide the future clinical development of bavituximab," said Joseph Shan, vice president of clinical and regulatory affairs at Peregrine. "It is encouraging that the initial biomarker analysis has identified an important biomarker early in the process and we are optimistic that additional biomarkers associated with improved outcomes for bavituximab-containing treatments will be identified as the analysis continues. We expect to be able to share the emerging data over the coming months at scientific and medical conferences as the more
results become available."

Mr. Shan continued, "It is not uncommon in the cancer field for therapeutic candidates to suffer clinical trial setbacks as researchers continue to learn more about the most appropriate patient populations for those drugs. In this landscape, biomarkers play an increasingly important role in helping identify specific patient characteristics that may impact responses to a treatment. This has been seen historically with targeted cancer treatments, as well as more recently with checkpoint inhibitors including PD-1 inhibitors. We look forward to identifying the equivalent markers for bavituximab that will help guide its clinical development."
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab is believed to override PS mediated immunosuppressive signaling by blocking the engagement of PS with its receptors as well as by sending an alternate immune activating signal. PS targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in multiple signs of immune activation and anti-tumor immune responses.

Peregrine’s clinical development strategy for bavituximab is currently focused on small, early-stage proof-of-concept trials evaluating the drug in combination with other cancer treatments. The intent behind this strategy is to control research and development costs, while continuing to generate clinical data to further validate bavituximab’s combination potential that will be critical to bringing onboard a partner to help advance the program.

Onconova to Host Key Opinion Leader Luncheon on Novel Approaches to Targeting the RAS Pathway in Oncology on Monday, October 17, in New York City

On October 10, 2016 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported that it will host a Key Opinion Leader lunch discussion on novel approaches to targeting the RAS Pathway in oncology, including the Company’s late-stage drug candidate, rigosertib, a small molecule that inhibits cellular signaling by interacting with the RAS-binding domain (RBD) of RAS effector proteins (Press release, Onconova, OCT 10, 2016, View Source [SID:SID1234515713]). The event and live webcast will take place on Monday, October 17, from 12:00 PM-1:30 PM Eastern Time in New York City.

The meeting will feature presentations by two pioneers in the area of RAS biology. Dr. Channing J. Der, a member of the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center and the Kenan Distinguished Professor in the Department of Pharmacology at UNC-Chapel Hill, and Dr. E. Premkumar Reddy, Professor in the Department of Oncological Sciences and the Department of Structural & Chemical Biology and Director of the Experimental Cancer Therapeutics Program at the Tisch Cancer Institute at Mount Sinai School of Medicine. Following these presentations, Onconova’s management team will provide an overview of the Company’s ongoing clinical development work with lead product candidate, rigosertib, a small molecule intended to treat patients with myelodysplastic syndromes (MDS). Onconova is actively enrolling patients in its global Phase 3 INSPIRE trial with IV rigosertib, and has completed an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) related to a combination therapy with oral rigosertib and azacitidine. A Q&A session with the featured experts and management will follow the presentations.

This event is intended for institutional investors and sell-side analysts. To reserve a place, please contact Mac McDonald at 212-915-2567 or via e-mail at [email protected]. A live webcast and subsequent replay of the event will be available at View Source

Mateon Announces Issuance of US Patent for Cathepsin Inhibition

On October 10, 2016 Mateon Therapeutics, Inc. (Nasdaq:MATN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, reported that the U.S. Patent and Trademark Office has issued U.S. Patent 9,458,103 to Mateon and Baylor University for "Compositions and methods for inhibition of cathepsins." The patent covers compounds which modulate cathepsin activity, particularly cathepsin L or cathepsin K, and methods of using these compounds for the treatment of conditions in which their regulation may be therapeutically useful.

"I am pleased to have this patent issued," stated William D. Schwieterman, M.D., President and Chief Executive Officer of Mateon. "For the past few years we have been working with Baylor University to pursue discovery and development of novel, small-molecule therapeutics that may be effective in oncology indications, and we are continuing several interesting, early-stage opportunities in this field."

Cathepsins have been validated as an important enzymatic class to target in drug discovery research, and eleven cysteine protease cathepsin enzymes have been identified to date in humans, with different structures and functions. Cathepsin L has a function in the growth and metastasis of primary tumors and has been implicated in diabetes, immunological responses, degradation of the articular cartilage matrix, and other pathological processes, including osteoporosis and rheumatoid arthritis. Inhibition of cathepsin L has also been shown to block Severe Acute Respiratory Syndrome (SARS) and Ebola pseudotype virus infection. Cathepsin K plays a role in bone resorption and has implications in osteoporosis.

CytRx Presents Interim Results from On-going Aldoxorubicin Plus Ifosfamide/Mesna Combination Clinical Trial at ESMO 2016 Congress

On October 10, 2016 CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, reported results from its on-going Phase 1b/2 trial of aldoxorubicin in combination with ifosfamide/mesna in patients with advanced sarcomas at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress being held in Copenhagen, Denmark.

Of the 36 evaluable patients receiving either 170mg/m2 or 250mg/m2 of aldoxorubicin plus ifosfamide and mesna, 13 of 36 (36%) achieved a partial response of the target lesion by RECIST 1.1 criteria, 22 of 36 (61%) had stable disease, and one patient had progressive disease. Median progression-free survival has not been reached, and dose-limiting toxicities were not observed in either cohort. No clinically significant cardiac toxicities were seen. The most common Grade 3 or 4 adverse events were neutropenia (71%), anemia (54%), thrombocytopenia (17%) and febrile neutropenia (14%). There were nine treatment-related serious adverse events, and no treatment-related deaths. The trial has been expanded to allow continued enrollment of additional sarcoma patients at the 250 mg/m2 dose of aldoxorubicin with ifosfamide and mesna.

"The results to date demonstrate that aldoxorubicin combined with ifosfamide provides significant clinical benefit for sarcoma patients," said Sant Chawla, M.D., F.R.A.C.P., the trial’s principal investigator and Director of the Sarcoma Oncology Center in Santa Monica, California. "More than one-third of sarcoma patients achieved a partial response for the target lesion and 61% had prolonged stable disease. Importantly, six patients with unresectable tumors achieved greater than 50% tumor shrinkage allowing some of them to become eligible for surgery. Further, we did not see any signs of cardiotoxicity including in patients that received approximately 10 times the cumulative maximum dose of doxorubicin."

The Phase 1b/2 clinical study is a single-center trial that has enrolled 40 patients to date with locally advanced, unresectable, and/or metastatic soft tissue sarcoma, intermediate-grade or high-grade chondrosarcoma or osteosarcoma. In the dose escalation phase, patients received either 170mg/m2 or 250mg/m2 of aldoxorubicin in combination with up to a 14-day continuous infusion of ifosfamide (1g/m2/day) plus mesna over a 28-day cycle. Up to six cycles of ifosfamide/mesna with aldoxorubicin can be administered, and aldoxorubicin may be continued until tumor progression or unacceptable toxicity occurs. The expansion phase will enroll patients at the 250mg/m2 dose of aldoxorubicin and will allow for patients that had received prior chemotherapy to be included. The primary endpoint of the study is safety, and secondary endpoints include overall response rates and progression-free survival.

About Aldoxorubicin

Aldoxorubicin is a rationally-engineered cytotoxic which combines doxorubicin, a widely used chemotherapeutic agent, with a novel linker molecule that binds directly and specifically to circulating albumin, the most abundant protein in the bloodstream. Protein-hungry tumors concentrate albumin, which facilitates the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. Typically, doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Using this acid-sensitive linker technology, aldoxorubicin delivers greater doses of doxorubicin (3 ½ to 4 times). To date, there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of doxorubicin in excess of 5,000 mg/m2. Aldoxorubicin is the first-ever single agent to show superiority over doxorubicin in a randomized global Phase 2b clinical trial in first-line STS.