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Argos Therapeutics Announces Completion of Patient Enrollment in Pivotal Phase 3 ADAPT Clinical Trial of AGS-003

On July 15, 2015 Argos Therapeutics reported the pivotal phase 3 ADAPT clinical trial of AGS-003 in combination with standard targeted therapy for the treatment of metastatic renal cell carcinoma (mRCC) has reached its enrollment goal of at least 450 randomized patients (Press release, Argos Therapeutics, JUL 15, 2015, View Source [SID:1234506335]).

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"Strong partnerships and coordination across our global study base to identify eligible patients and collect tumor samples have led to successful enrollment for the largest clinical trial ever conducted in patients with newly diagnosed, unfavorable risk, synchronous metastatic RCC," said ADAPT trial co-principal investigator and lead medical oncologist Dr. Robert Figlin, the Steven Spielberg Family chair in hematology oncology and professor of medicine and biomedical sciences at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute. "With enough patients screened with successful tumor collection to meet and exceed our target of 450 randomized patients, we look forward to shifting our full attention to the treatment phase of the study and expected data readouts in 2016."

AGS-003 is an autologous dendritic-cell based immunotherapy designed to induce a memory T-cell response specific to each patient’s unique tumor antigens. It is produced using a small sample from a patient’s own tumor and dendritic cells derived from a leukapheresis procedure. In an open-label phase 2 study, treatment with AGS-003 plus sunitinib yielded a median overall survival of more than 30 months in newly diagnosed, unfavorable risk mRCC patients.

To qualify for the ADAPT trial, patients were required to be good candidates for standard surgery and targeted drug therapy. During the enrollment process approximately 55 percent of patients who consented for tumor collection and screening for the treatment phase of the trial were found to be ineligible for treatment because of non-clear cell histology, lack of suitability to initiate standard targeted drug therapy, poor performance status, poor prognosis after surgery, a lack of evaluable metastatic disease, or other factors.

"By concluding enrollment in the ADAPT trial, we have reached an exciting milestone by demonstrating the ability to rapidly screen and collect tumor samples for more than 1,000 newly diagnosed metastatic RCC patients over the course of approximately two years," said ADAPT trial co-principal investigator and lead urologic oncologist Dr. Christopher Wood, professor of urology and deputy chairman of the department of urology, division of surgery at the University of Texas MD Anderson Cancer Center. "This would not have been possible without a strong multidisciplinary collaboration among urologists and oncologists, which positions us well to advance our evaluation of AGS-003 in addition to standard treatment through trial completion."

"The ADAPT trial is focused on a population with significant unmet needs as the expected median survival based upon International mRCC Database Consortium (IMDC) benchmarks is approximately 15 months after diagnosis, even with standard surgery and approved targeted therapies," said Doug Plessinger, vice president of clinical and medical affairs for Argos Therapeutics. "We continue to believe that the combination of standard treatment with our personalized immunotherapy has the potential to bring new hope to mRCC patients, and we look forward to the next interim data review from the ADAPT trial in the first part of 2016."

About the Arcelis Technology Platform

Arcelis is a fully personalized immunotherapy technology that captures mutated and variant antigens that are specific to each patient’s disease. It is designed to overcome immunosuppression by producing a durable memory T-cell response without adjuvants that may be associated with toxicity. The technology is potentially applicable to a wide range of different cancers, and is designed to overcome many of the manufacturing and commercialization challenges that have impeded other personalized cancer immunotherapies. The Arcelis process uses only a small tumor or blood sample and the patient’s own dendritic cells, which are collected and optimized following a single leukapheresis procedure. The proprietary process uses RNA isolated from the patient’s disease sample to program dendritic cells to target disease specific antigens. The activated, antigen-loaded dendritic cells are then formulated into the patient’s plasma and administered via intradermal injection.

Radius Health Today Announced Preclinical Data for Its Investigational Drug RAD1901 in Combination With CDK and mTOR Inhibitors

On July 15, 2015 Radius Health reported that early but promising preclinical data show that its investigational drug RAD1901, in combination with CDK4/6 inhibitors, such as Pfizer’s palbociclib and mTOR inhibitors, such as Novartis’ everolimus, was effective in shrinking tumors (Press release, Radius, JUL 15, 2015, View Source [SID:1234506343]).

In breast cancer models using patient derived xenografts with either wild type or mutant ESR1, treatment with RAD 1901 resulted in marked tumor growth inhibition, but the combination of RAD1901 with either agent, palbociclib or everolimus, showed anti-tumor activity that was significantly greater than either agent alone. RAD1901 is being evaluated at high doses as a Selective Estrogen Receptor Degrader (SERD) for potential use in metastatic breast cancer.

In addition to this preclinical study, Radius has also recently completed a pharmacokinetic/ pharmacodynamic study in healthy volunteers. In total, 52 subjects were treated with doses between 200 mg and 1000mg for up to 7 days. Preliminary data suggested that all doses were generally well tolerated. A subset of subjects received baseline and FES-PET after 7 days to evaluate ER signal attenuation, and we expect to report the final results of this study in the third quarter of this year.

Separately, an abstract titled "RAD1901: a novel, orally bioavailable selective estrogen receptor degrader that demonstrates antitumor activity in breast cancer xenograft models" of the preclinical characterization, anti-tumor activity and therapeutic potential of investigational drug RAD1901 in breast cancer has been published in the online journal Anti-Cancer Drugs, and can be found at View Source

"These data provide Radius with important insights to evaluate multiple options including combination therapies as we seek to accelerate the next phases of our clinical development program for RAD1901 in metastatic breast cancer," said Robert E. Ward, President and CEO of Radius Health.

Radius is currently screening and enrolling patients in a Phase 1 multicenter, open-label, two-part, dose-escalation study of the investigational drug RAD1901 in postmenopausal women with advanced estrogen receptor positive and HER2-negative breast cancer. The study is designed to determine the recommended Phase 2 dose of RAD1901, and includes a preliminary evaluation of the potential anti-tumor effects. Following the determination of an optimal dose, Radius plans to initiate trials in a larger expansion cohort to evaluate the potential role of the investigational drug RAD1901 in combination with currently available therapies.

About the Investigational Drug RAD1901

Radius is developing the investigational drug RAD1901 as a potential treatment for estrogen positive (ER+) cancers, like breast, ovarian or endometrial cancer. Currently, Radius is focusing its clinical research activities in breast cancer. The National Cancer Institute estimates that approximately 70% of breast cancers are ER+ and may grow in response to exposure to estrogen. Endocrine therapy is intended to block the estrogen signal or reduce the production of estrogen. More information about breast cancer and endocrine therapy may be found on the National Cancer Institute website View Source

RAD1901 is an investigational, non-steroidal small molecule that is designed to selectively bind and degrade the ER. RAD1901 has demonstrated potent anti-tumor activity in xenograft models of ER+ breast cancer in preclinical testing and complete suppression of the FES-PET signal after six days of dosing in a maximum tolerated dose clinical study. In preclinical models thus far, RAD1901 has shown good tissue selectivity, does not appear to stimulate the uterine endometrium, and appears to protect against bone loss in an ovariectomy-induced osteopenia rat model. In addition, we believe that RAD1901 also has the ability to cross the blood-brain barrier. In vitro, treatment of human breast cancer cell lines with the investigational drug RAD1901 resulted in degradation of the ER and inhibition of both basal and estradiol-stimulated proliferation.

Radius has begun a Phase 1 multicenter, open-label, two-part, dose-escalation study of the investigational drug RAD1901 in postmenopausal women with advanced estrogen receptor positive and HER2-negative breast cancer. The study is designed to determine the recommended Phase 2 dose of RAD1901, and includes a preliminary evaluation of the potential anti-tumor effects. The incidence of dose limiting toxicities will be assessed during the first 28 days. Tumor response will be evaluated in patients with measurable or evaluable disease, using RECISTv1.1 guidelines every 8 weeks until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months of treatment. Plasma concentrations of RAD1901 will be assessed every 28 days for up to 12 months of treatment. The details of the Phase 1 study of RAD1901 are posted on www.clinicaltrials.gov.

Radius is also developing RAD1901 at lower doses as a Selective Estrogen Receptor Modulator (SERM) , for the potential treatment of vasomotor symptoms. Historically, hormone replacement therapy ("HRT") with estrogen or progesterone was considered the most efficacious approach to relieving menopausal symptoms such as hot flashes. However, because of the concerns about the potential long‑term risks and contraindications associated with HRT, Radius believes a significant need exists for new therapeutic treatment options to treat vasomotor symptoms. In a Phase 2 proof of concept study, RAD1901 at lower doses demonstrated a reduction in the frequency and severity of moderate and severe hot flashes. Radius intends to commence a Phase 2b trial in vasomotor symptoms in the second half of 2015.

Five Prime Therapeutics Establishes Strategic Research Collaboration and License Agreement With Inhibrx for Novel GITR Antibodies

On July 15, 2015 Five Prime Therapeutics reported a strategic research collaboration and license agreement with Inhibrx for Inhibrx’s novel glucocorticoid-induced tumor necrosis factor receptor (GITR) antibody program, which is currently at lead selection stage (Press release, Five Prime Therapeutics, JUL 15, 2015, View Source [SID:1234506340]).

Leveraging its comprehensive protein library and proprietary in vivo screening technologies, Five Prime identified GITR as one of the most potent inhibitors of tumor growth. GITR is an immune checkpoint protein that is selectively expressed on effector T cells and T regulatory cells (Tregs), and is believed to activate an immune response against tumor cells. In preclinical studies, agonist antibodies have demonstrated the ability to induce tumor regressions, particularly when administered in combination with other immuno-oncology therapies.

Inhibrx’s technology offers a novel, potentially best-in-class approach for engineering a GITR antibody with the desired properties aimed at maximizing safety, efficacy and combinability with other therapies. Inhibrx’s multivalent antibody scaffolds are designed to multimerize and activate GITR independent of Fc binding. This is in contrast to conventional GITR antibodies, where efficacy is dependent upon binding and the presence of Fc-receptor bearing cells and may vary due to Fc receptor polymorphisms and be dampened by competing serum IgG.

Under the terms of the agreement, Five Prime will pay Inhibrx a $10 million license fee in return for exclusive, worldwide therapeutic and diagnostic rights to antibodies provided by Inhibrx that bind to GITR, as well as an option to license multi-specific antibodies that bind to GITR and other targets. Inhibrx is eligible to receive up to $342.5 million in development, regulatory and commercial milestone payments per therapeutic product, or up to $442.5 million in development, regulatory and commercial milestone payments if the U.S. Food and Drug Administration grants a Breakthrough Therapy Designation to such therapeutic product. Milestone payments for development, regulatory and first commercial sale events may be paid in cash or in Five Prime common stock at Five Prime’s discretion. Inhibrx is also eligible for low double-digit tiered royalties on future product sales.

"Five Prime is actively pursuing a comprehensive approach to immuno-oncology by identifying pipeline candidates with the potential to work independently or in combination to target macrophages, immune check points, T cell agonist pathways and Treg cells. Comparing across many potential targets, our platform pointed to GITR as an ideal agonist to expand our portfolio," said Lewis "Rusty" T. Williams, M.D., Ph.D., chief executive officer & president of Five Prime. "Inhibrx’s antibody technology is uniquely suited to activate GITR and enhance the immune response against the tumor. We believe this program has the potential to create a differentiated, next-generation GITR agonist that may have broad therapeutic application as a monotherapy or in combination with approved checkpoint inhibitors or other therapies, including products in our pipeline."

"We believe Five Prime’s insights into GITR biology and their scientific and clinical translation capabilities make them the optimal partner for our GITR program," said Mark Lappe, CEO of Inhibrx. "They share our commitment to bring therapeutics to patients in need as quickly as possible and we are excited to be collaborating with them."

Five Prime intends to provide updated cash guidance when it reports its second quarter 2015 financial results.

RedHill Biopharma Extends Option Agreement for Phase II-Stage Pancreatic Cancer Drug RP101

On July 15, 2015 RedHill Biopharma reported that it has elected to extend its August 2014 exclusive option agreement with RESprotect GmbH, a privately-held German-based biotech company for the acquisition of the oncology drug candidate RP101 (Press release, RedHill Biopharma, JUL 15, 2015, View Source [SID:1234506339]).

RP101 is a proprietary, first-in-class, orally-administered, heat shock protein 27 (Hsp27) inhibitor intended to prevent the induction of resistance to chemotherapy (chemoresistance), thus maintaining sensitivity of the tumor to chemotherapy and potentially enhancing patient survival. RP101 has completed several clinical studies, including a Phase II study in pancreatic cancer and has been granted Orphan Drug designation for the adjunct treatment of pancreatic cancer by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

Under the terms of the binding exclusive option agreement with RESprotect GmbH, RedHill has the option to acquire the worldwide exclusive rights to RP101 for all indications, other than for the pancreatic cancer indication in South Korea. If RedHill elects to exercise this option, it will acquire the exclusive rights to RP101 for a total payment of $100,000, for both the exercise option and the acquisition of the rights, as well as potential milestone payments and tiered royalties on net revenues, ranging from single digits to mid-teens. RedHill has agreed to pay $25,000 for a one-year extension of the option agreement.

RedHill recently commenced a preclinical development program for RP101 to examine the efficacy of the drug candidate in various tumor models. The preclinical program is intended to support the existing clinical data and to assess a potential clinical development path for RP101.

About RP101:

RP101 is a nucleoside analogue found by Prof. Rudolf Fahrig at the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) in Hannover, Germany, to inhibit development of chemoresistance in various cancer models. It is an orally-administered, patent-protected small molecule which binds to heat shock protein 27 (Hsp27) and inhibits its multidrug-resistance gene amplification activity. Hsp27 is a chaperone protein which is found in abnormally high levels in cancer cells. The overexpression of Hsp27, which results in the amplification of a multidrug-resistance (MDR) gene, has been linked to tumor resistance to cytotoxic drugs and the development of metastasis. By inhibiting Hsp27, RP101 may prevent the induction of resistance to chemotherapy (chemoresistance) and maintain sensitivity of tumors to chemotherapy, thus potentially enhancing patient survival. RP101 has been studied in several Phase I and Phase II clinical studies with a total of 249 subjects treated, including a Phase II study in pancreatic cancer. RP101 has been granted Orphan Drug designation for the adjunct treatment of pancreatic cancer by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

Mersana Therapeutics and Recepta Biopharma S.A. Enter License Agreement for Novel Antibody

On July 14, 2015 Mersana Therapeutics, Inc. and Recepta Biopharma S.A. reported that they have entered into an exclusive license agreement in which Mersana will use its proprietary Fleximer technology to develop and commercialize an immunoconjugate with the undisclosed cancer antibody licensed from Recepta (Press release, Mersana Therapeutics, JUL 14, 2015, View Source [SID1234609623]).

Under the terms of the agreement, Recepta will provide Mersana exclusive rights to its novel monoclonal antibody to an undisclosed target, and Mersana will leverage Fleximer to develop an immunoconjugate against the target. Financial terms of the agreement include an upfront payment and subsequent payments to Recepta, which together could total $86 million plus royalties if certain development, regulatory and commercial milestones are achieved. Mersana will conduct and fund clinical development and regulatory activities. Recepta will have rights to commercialize in Brazil, while Mersana will have rights to commercialize in the rest of the world. Mersana will be eligible to receive royalties from Recepta on sales in Brazil.

"This licensing deal with Mersana follows pioneering R&D conducted by Recepta with this antibody, which was discovered by Ludwig Cancer Research, our partner and a global nonprofit research organization. It will enable the development of a novel immunoconjugate that has the potential to improve patient outcomes in oncology," said José Fernando Perez, PhD, Chief Executive Officer of Recepta.

"We are excited to develop a Fleximer-based immunoconjugate with this antibody to address unmet needs in cancer," said Anna Protopapas, President and Chief Executive Officer of Mersana. "This will expand our pipeline of oncology therapies that address the limitations of currently available antibody-drug conjugates and complement our objective to pursue one IND each year, starting with XMT-1522 later this year."