1stOncology™: Cancer Intelligence Service – Page 15669 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Tarveda Therapeutics Announces Phase 1/2a Clinical Trial of PEN-221 Underway in Patients with Neuroendocrine Tumors and Small Cell Lung Cancer

On January 4, 2017 Tarveda Therapeutics a biopharmaceutical company discovering and developing Pentarins as a new class of potent and selective anti-cancer medicines, reported that a Phase 1/2a clinical trial evaluating PEN-221 in patients with advanced neuroendocrine tumors and small cell lung cancer expressing the somatostatin receptor 2 (SSTR2) is underway, with patients enrolled and treated (Press release, Tarveda Therapeutics, JAN 4, 2017, View Source [SID1234517269]). The somatostatin receptor is highly expressed in neuroendocrine cancers. PEN-221 is a novel, miniaturized drug conjugate designed to selectively target SSTR2 and then internalize and release its potent DM1 payload in the tumor cell.

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!

"Pentarins are engineered to rapidly penetrate and kill solid tumors that have proven challenging for treatment modalities such as antibody drug conjugates and chemotherapeutics," said Gordon B. Mills, M.D., Ph.D., Professor and Chair, Department of Systems Biology, at The University of Texas MD Anderson Cancer Center, Houston, TX. "The miniaturized size, unique design and potent payloads of Pentarins allow for sustained payload release in solid tumors to drive potential efficacy while sparing normal tissue.

"PEN-221 has high affinity for the SSTR2 on the surface of neuroendocrine and small cell lung cancer cells, which facilitates internalization followed by release of its potent cell-killing payload, DM1. Pentarins offer a new treatment approach to address the deficits of current treatments, and PEN-221 has the potential to address the urgent and significant medical need of patients with neuroendocrine and small cell lung cancers. Having an imaging approach to identify neuroendocrine and small cell lung cancers expressing the somatostatin receptor 2 makes the PEN-221 trial an exciting proof-of-concept as well as an opportunity for patients with these challenging tumors," concluded Mills.

The Phase 1/2a first-in-human study is an open-label, multicenter trial to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of PEN-221 in patients with SSTR2-expressing advanced neuroendocrine cancers, including a range of neuroendocrine tumors and small cell lung cancer. Utilizing FDA-approved imaging diagnostics, the study employs a seamless, Phase 1/2a design that identifies and selects advanced cancer patients with SSTR2 expressing tumors. These patients are believed to be the most likely to benefit from treatment with PEN-221. For additional information on this clinical trial, please visit clinicaltrials.gov, identifier number NCT02936323.

"The initiation of this Phase 1/2a clinical trial of PEN-221 in patients with neuroendocrine tumors and small cell lung cancer marks an important milestone in the development of this product candidate and our Pentarin drug conjugates," said Leila Alland, M.D., Chief Medical Officer of Tarveda. "PEN-221 consistently demonstrated complete and durable regressions in hard-to-treat xenograft cancer models. We and our industry leading clinical investigators are excited to advance this therapy into the clinic."

About Pentarins
Tarveda is developing Pentarins, potent and selective miniaturized drug conjugates with high affinity for specific cell surface and intracellular targets. Pentarins are engineered to bind to their tumor cell targets and provide sustained release of their potent therapeutic payloads deep into solid tumor tissue. Comprised of a targeting ligand conjugated to a potent cell-killing agent through a chemical linker, Pentarins are designed to overcome the deficits of both larger antibody drug conjugates and small molecules that limit their therapeutic effectiveness against solid tumors. Together, the components of Tarveda’s Pentarins have distinct, yet synergistic, anticancer attributes: the small size of Pentarins allows for effective penetration and distribution into the tumor tissue, the ligand’s targeting ability allows for specific binding and retention in tumor cells, and the chemical linker is tuned to optimize the release of the potent, cell-killing payload inside the cancer cells for efficacy.

BAVARIAN NORDIC PROVIDES UPDATE ON ANTICIPATED TIMING OF PROSPECT STUDY

On January 4, 2017 Bavarian Nordic A/S (OMX: BAVA, OTC: BVNRY) reported guidance for the current estimated timing of interim and final overall survival analysis from the PROSPECT study – a placebo controlled Phase 3 study designed to investigate the efficacy of PROSTVAC to prolong the survival of men with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Bavarian Nordic, JAN 4, 2017, View Source [SID1234517268]).

The company maintains its previous guidance that full data is expected within this year, albeit in the second half of 2017, with the third interim analysis likely to occur around mid-2017. This estimate is based on a decline in the number of average monthly events currently seen in the PROSPECT study.

"As there has been speculation that the third interim could occur during first quarter of 2017, we believe it is important to update the market on the current estimated timelines for readout of the Phase 3 study" said Paul Chaplin, President and CEO of Bavarian Nordic.

While the company remains blinded to all patient specific data, the latest estimates have been provided by the independent Data Monitoring Committee (DMC) following a routine analysis of the current survival data.

"While we will have to await the final read out of the PROSPECT study to establish the efficacy of PROSTVAC, we are encouraged that the current monthly event rate has declined. This is great news for the patients. Not only is this consistent with an improvement in the standard of care for patients with mCRPC, which has been observed in recent years, but could also be indicative of a therapeutic effect of PROSTVAC as well" said Paul Chaplin.

About the PROSPECT study
PROSPECT is a global, randomized, double-blind, placebo-controlled phase 3 study being conducted under a Special Protocol Assessment (SPA) from the FDA. The objective of the study is to determine whether PROSTVAC alone or in combination with GM-CSF is effective in prolonging overall survival. The study has been fully enrolled with 1,297 asymptomatic or minimally symptomatic mCRPC patients as of January 2015. Patients were enrolled at more than 200 sites in 15 countries. Both the first and second interim analyses confirmed that the study would continue as planned. Final study data requires 534 events in both comparisons of treatment arms versus placebo, and the third interim analysis will occur at 427 events.

About PROSTVAC
PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec, or "rilimogene") is a prostate specific antigen (PSA)-targeted immunotherapy candidate designed to enhance or stimulate the body’s immune response, specifically T cells that will home to and kill prostate cancer cells, altering the course of the disease and improving overall survival (OS) of patients with prostate cancer. A robust data package has been established that includes 18 ongoing or completed clinical studies, comprising more than 2,000 patients of which more than 1,100 patients have been actively treated with PROSTVAC, which has been generally well-tolerated. A randomized, placebo-controlled Phase 2 trial demonstrated the potential of PROSTVAC to extend the median overall survival by 8.5 months in patients with advanced prostate cancer. These results led to the initiation of the PROSPECT pivotal Phase 3 study.

PROSTVAC is being developed in collaboration with the National Cancer Institute under a Cooperative Research and Development Agreement.

Five Prime Therapeutics and Bristol-Myers Squibb Extend Research Term in Collaboration to Discover Novel Immuno-Oncology Therapies for Three Immune Checkpoint Pathways

On January 4, 2017 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that Bristol-Myers Squibb Company (NYSE:BMY) has exercised its option to extend the research term of its discovery collaboration agreement with Five Prime for the discovery, development and commercialization of immuno-oncology therapies directed toward targets in three undisclosed immune checkpoint pathways (Press release, Five Prime Therapeutics, JAN 4, 2017, View Source [SID1234517266]).

The original collaboration agreement was established in March 2014 and focused on two undisclosed immune checkpoint pathways. In January 2016, the companies added a third immune checkpoint pathway to the collaboration. Bristol-Myers Squibb has now elected to extend the research term from its original ending date of March 2017 to March 2018, and will provide additional research funding for the 12-month extension of the research term.

Bristol-Myers Squibb will utilize Five Prime’s discovery capabilities to advance these three immuno-oncology programs toward the identification of drug candidates for continued research and development. Drug candidates developed against targets in these pathways may be studied either as single agents or in combination with approved Bristol-Myers Squibb immuno-oncology therapies or others in development. Five Prime and Bristol-Myers Squibb continue work on antibody drug candidates targeting these pathways. Bristol-Myers Squibb has advanced the first antibody from this collaboration to IND-enabling activities.

"We are pleased that the demonstrated productivity of our unique research capabilities has prompted Bristol-Myers Squibb, a clear leader in immuno-oncology, to invest further in our efforts to find new drug candidates to modulate three checkpoint pathways," said Luis Borges, Ph.D., senior vice president of research, at Five Prime. "Together, we have made significant progress that includes an antibody candidate that could lead to an IND application for our collaborator."

Under the terms of the original agreement, Bristol-Myers Squibb will obtain exclusive, worldwide rights to develop and commercialize products directed toward certain protein targets in the three checkpoint pathways identified by Five Prime prior to and during the collaboration. Bristol-Myers Squibb paid an upfront fee of $20 million to Five Prime and will provide up to $11.6 million in research funding over the course of the entire research term. Five Prime will be eligible to receive up to $300 million in future development (including $5 million upon filing of the first IND application by Bristol-Myers Squibb), regulatory and sales-based milestone payments per collaboration product and tiered mid-single-digit rising to low-double-digit royalty payments on net sales of each product commercialized by Bristol-Myers Squibb.

Affimed and MD Anderson Announce Clinical Immuno-Oncology Development Collaboration

On January 4, 2017 Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies, and The University of Texas MD Anderson Cancer Center reported an exclusive strategic clinical development and commercialization collaboration to evaluate Affimed’s TandAb technology in combination with MD Anderson’s natural killer cell (NK) product (Filing, 6-K, Affimed, JAN 4, 2017, View Source [SID1234517262]).

NK-cells are white blood cells which monitor the body for infected and cancerous cells. The technology to grow NK-cells from umbilical cord blood was developed at MD Anderson.

This collaboration will leverage MD Anderson’s expertise in NK-cells and translational medicine, and Affimed’s capabilities to develop tumor-targeting bispecific TandAb immune cell engagers.

"In our effort to broaden the applications of our NK-cell engager products, we are excited to partner with the world-leading NK-cell experts at MD Anderson to investigate their unique product together with our first-in-class NK-cell engager AFM13 in Hodgkin lymphoma," said Adi Hoess, Ph.D., CEO of Affimed. "Harnessing the advantages of both antibody-based and cell therapy approaches has the potential to better exploit the therapeutic activity of NK-cells. We believe this partnership could benefit many hematological malignancies, including in multiple myeloma, where Affimed is developing AFM26, a BCMA/CD16A bispecific antibody. For us, this partnership is an important step in executing our strategy to develop transformative cancer therapies."

Collaborative studies will research, develop, and eventually commercialize novel oncology therapeutics resulting from this combination of products. MD Anderson will be responsible for conducting preclinical research activities aimed at investigating its NK-cells derived from umbilical cord blood in combination with Affimed’s lead NK-cell engager, the CD30- and CD16A-targeting TandAb AFM13. These are intended to be followed by a Phase 1 clinical trial. Affimed will fund research and development expenses for this collaboration and the agreement includes a provision for the potential expansion of the partnership. Affimed holds an option to exclusive worldwide rights to develop and commercialize any product developed under the collaboration.

"We look forward to joining the cord blood-derived NK-cells developed at MD Anderson with our collaborator’s technology which we believe will benefit our patients," said Katayoun Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson.

AFM13 is a bispecific NK-cell TandAb simultaneously targeting CD16A on NK-cells and CD30 on tumor cells. AFM13 is designed to treat CD30-positive malignancies including Hodgkin lymphoma (HL) and T-cell lymphoma (TCL) and is currently in Phase 2 development in HL patients. Based on its safety profile, AFM13 is being developed both as monotherapy and in combination with other therapeutics such as Merck’s checkpoint inhibitor KEYTRUDA.

Elizabeth Shpall, M.D., professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson, and Rezvani’s co-leader on the project, believes the collaboration "holds true potential to produce a novel cellular therapeutic for the treatment of high-risk Hodgkin lymphoma."

CytRx Granted Type B Pre-NDA Meeting with U.S. FDA for Registration Pathway with Aldoxorubicin as a Treatment for Patients with Relapsed Soft Tissue Sarcomas

On January 4, 2017 CytRx Corporation (NASDAQ: CYTR), a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing new therapeutics to treat patients with cancer, reported that, in response to a request from the company, the U.S. Food and Drug Administration (FDA) has agreed to a Type B pre-NDA meeting at which the company will seek input on its planned New Drug Application (NDA) for aldoxorubicin as a new second-line treatment for patients with soft tissue sarcomas (STS) (Press release, CytRx, JAN 4, 2017, View Source [SID1234517261]). Assuming a positive outcome from this pre-NDA meeting, CytRx expects to submit an NDA for aldoxorubicin to the FDA in the last quarter of 2017, and, subject to FDA approval, bring aldoxorubicin to market next year.

"Based on positive, statistically significant results from our pivotal Phase 3 trial evaluating aldoxorubicin compared to investigator’s choice in patients with previously treated relapsed or refractory sarcomas, we requested, and were recently granted, a Type B meeting with the FDA," said Daniel Levitt, M.D., Ph.D., Chief Operating Officer and Chief Medical Officer of CytRx. "The purpose of this meeting is to share the Phase 3 data with the Agency and discuss the regulatory path forward for aldoxorubicin. In our view, this meeting is an important next step toward our goal of bringing aldoxorubicin to the thousands of patients in need of a new treatment for relapsed soft tissue sarcoma."

Overview of the Updated Phase 3 Trial and Results

The randomized, controlled Phase 3 trial enrolled a total of 433 patients at 79 clinical sites. Patients with metastatic, locally advanced or unresectable soft tissue sarcomas who had either not responded to, or who had progressed following treatment with one or more systemic regimens of non-adjuvant chemotherapy were randomized 1:1 to be treated with aldoxorubicin or the investigator’s choice of an approved chemotherapeutic regimen, including doxorubicin, ifosfamide, dacarbazine, pazopanib (Votrient), or gemcitabine plus docetaxel. The primary endpoint of the study is PFS. Secondary endpoints include overall survival, response rates, disease control rates and safety.

In November 2016, CytRx reported positive results which demonstrated a statistically significant improvement in progression-free survival (PFS) between aldoxorubicin and investigator’s choice therapy in 246 patients with leiomyosarcoma and liposarcoma, (p=0.007). The hazard ratio (HR) was 0.62 (95% CI 0.44-0.88), representing a 38% reduction in the risk of tumor progression for patients receiving aldoxorubicin versus investigator’s choice. Leiomyosarcoma and liposarcoma are the two most common types of STS and accounted for 57% of the patients enrolled in the trial. Aldoxorubicin also demonstrated a statistically significant improvement in PFS over investigator’s choice in 312 patients treated in North America (p=0.028; HR=0.71, 95% CI 0.53-0.97). Notably, aldoxorubicin performed better than investigator’s choice for the entire study population and narrowly missed statistical significance (p=0.12; HR=0.81, 95% CI 0.64-1.06). All responses were determined by an independent, blinded central lab assessment of scans.

Aldoxorubicin did not cause clinically significant cardiac, renal, or hepatic toxicities. For the global trial population, the most commonly reported adverse events were neutropenia and anemia consistent with prior clinical trials with aldoxorubicin. Grade 3 or higher adverse events were manageable with supportive care and occurred at a rate of 61% for patients receiving aldoxorubicin and 46% in patients treated with investigator’s choice. Importantly, treatment-emergent adverse events leading to discontinuation occurred in 4.2% of patients treated with aldoxorubicin, compared to 6.3% for patients receiving investigator’s choice.

Patients continue to be followed for overall survival (OS), a secondary endpoint, and CytRx expects the OS data to be available in 2017.

About Soft Tissue Sarcoma

Soft tissue sarcoma is a cancer occurring in muscle, fat, blood vessels, tendons, fibrous tissues and connective tissue. It can arise anywhere in the body at any age. STS remains a high unmet medical need because of the difficulty in treating the more than 50 types of this aggressive cancer. According to the American Cancer Society, in 2016 more than 12,300 new cases were diagnosed in the U.S. and approximately 5,000 Americans died from this disease. In addition, approximately 40,000 new cases and 13,000 deaths in the U.S. and Europe are part of a growing underserved market.

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 drug well in excess of 6,500 mg/m2 of doxorubicin equivalents. Aldoxorubicin is the first-ever single agent to show superiority over doxorubicin in a randomized clinical trial in first-line STS.