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CytRx Announces Initial Results of Phase 3 Trial of Aldoxorubicin in Patients with Second-Line Soft Tissue Sarcoma; Subsequent Analysis to Be Announced Fourth Quarter 2016

On July 11, 2016 CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, reported the results of an analysis of its global, randomized, Phase 3 clinical trial of aldoxorubicin compared to investigator’s choice therapy in patients with relapsed or refractory soft tissue sarcomas (STS) (Press release, CytRx, JUL 11, 2016, View Source;p=RssLanding&cat=news&id=2184496 [SID:1234513826]).

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In accordance with the FDA-granted special protocol assessment, the current analysis occurred following 191 progression events. Because enrollment was interrupted by a partial clinical hold in November 2014, this analysis did not provide for sufficient follow-up for the nearly two-thirds of patients who entered the Phase 3 study after the hold was resolved and enrollment resumed. This resulted in nearly half of all patients being censored (excluded) from the current progression free survival (PFS) evaluation. CytRx expects to conduct a second analysis, which will include longer patient follow-up and allow for greater maturation of all endpoints. The Company expects to announce the results of this evaluation and hold an end-of-Phase 3 meeting with the Food and Drug Administration (FDA) in the fourth quarter of 2016. The partial clinical hold was related to a single patient enrolled in a compassionate use study, which was subsequently resolved successfully.

For the current evaluation, the study did not show a significant difference between aldoxorubicin and investigator’s choice therapy for PFS, with a median of 4.17 months and 4.04 months, respectively, for the study’s primary endpoint (hazard ratio: 0.91). However, the most immediate indications of therapeutic activity, objective response rate (ORR) and disease control rate (ORR + stable disease ≥ 4 months), showed a near doubling in the aldoxorubicin arm compared to investigator’s choice, including in patients who previously received treatment with doxorubicin. Disease control rate for aldoxorubicin was significantly greater than investigator’s choice therapy in the intent-to-treat population (p=0.048) as well as in patients who received prior doxorubicin (p=0.0415). Patients continue to be followed for overall survival (OS), a secondary endpoint of the trial.

"While results from this current analysis are immature, a near doubling of response rates with aldoxorubicin suggests a highly active therapy which may benefit certain patients with soft tissue sarcoma," said Sant Chawla, M.D., F.R.A.C.P., Principal Investigator and the Director of the Sarcoma Oncology Center in Santa Monica, California. "Because enrollment was interrupted by a clinical hold, both PFS and response data need to be analyzed at a future date to account for patients enrolled later in the trial. I look forward to this subsequent analysis providing a more complete understanding of aldoxorubicin’s potential in this very challenging disease."

Treatment-related adverse events for aldoxorubicin were consistent with those observed in prior studies. Aldoxorubicin was not associated with clinically significant cardiac, kidney or liver toxicities. The Company plans to present updated results of the study at an upcoming medical meeting.

"The complexity, in terms of tumor diversity and primary location, makes soft tissue sarcoma extremely difficult to treat, especially in the relapsed and refractory setting, resulting in few treatment advances over the last four decades," said Daniel Levitt, M.D., Ph.D., Executive Vice President and Chief Medical Officer of CytRx. "This first-of-its-kind study in STS included a comparator arm with multiple regimens, allowing for treatments to be matched to specific sarcoma subtypes. Despite a requirement for this challenging study design, aldoxorubicin demonstrated markedly greater activity over investigator’s choice therapy. That said, the unforeseen clinical hold that interrupted this study impacted the outcome of the current evaluation, underscoring a need for a subsequent analysis."

"In over 550 patients treated to date, aldoxorubicin has demonstrated anti-tumor activity in multiple tumor types and has shown a manageable safety profile," said Steven A. Kriegsman, CytRx’s Chairman and CEO. "With approximately $68.2 million in cash and equivalents as of our last 10-Q filing, CytRx is funded through the next Phase 3 STS trial analysis and through a readout of our global Phase 2b trial of aldoxorubicin in small cell lung cancer. We are deeply grateful for the continued support and commitment of the patients, their families, the investigators and clinical support professionals participating in the Phase 3 trial."

Celldex Therapeutics Initiates Phase 1/2 Clinical Trial of New Product Candidate CDX-014 in Advanced Renal Cell Carcinoma

On July 11, 2016 Celldex Therapeutics, Inc. (Nasdaq:CLDX) reported that enrollment has opened in its Phase 1/2 study of CDX-014 in advanced renal cell carcinoma (RCC) (Press release, Celldex Therapeutics, JUL 11, 2016, View Source [SID:1234513825]). CDX-014 is a novel antibody-drug conjugate that targets the transmembrane protein T-cell immunoglobulin mucin-1 (TIM-1). TIM-1 expression is upregulated in several cancers, most notably renal cell and ovarian carcinomas, and is associated with a more malignant phenotype of RCC and tumor progression1,2. TIM-1 has very restricted expression in healthy tissue. The study is open to patients with both clear cell and papillary RCC.

"Although significant advances have been made in the treatment of metastatic renal cell carcinoma, patients who progress through currently approved therapies have extremely limited options," said Thomas Davis, M.D., Executive Vice President and Chief Medical Officer of Celldex Therapeutics. "Selectively targeting TIM-1, which is expressed in the majority of metastatic renal cell carcinomas, presents a novel approach that could provide new options for patients. CDX-014 has also demonstrated an ability to effectively kill tumor cells without negatively impacting immune response in preclinical studies, which may make it an ideal candidate for future combination therapy. We are pleased to initiate this first study of CDX-014, further broadening our pipeline to meet the needs of patients with difficult to treat cancers."

The Phase 1 dose-escalation portion of the study will evaluate cohorts of patients receiving increasing doses of CDX-014 to determine the maximum tolerated dose and a recommended dose for Phase 2 study. The Phase 2 portion of the study will enroll approximately 25 patients to assess the anti-tumor activity of CDX-014 at the recommended dose in advanced renal cell carcinoma as measured by objective response rate (RECIST 1.1). Secondary objectives include safety and tolerability, pharmacokinetics, immunogenicity and additional measures of anti-tumor activity, including clinical benefit rate. The study is being conducted in the United States and is expected to include approximately 10 sites. Patients must have advanced/metastatic clear cell or papillary renal cell carcinoma and have experienced progressive disease after at least two prior lines of therapy, including at least one VEGF-targeted tyrosine kinase inhibitor, or be otherwise inappropriate candidates for all approved therapies. Data analysis will be conducted separately in clear cell RCC and papillary RCC, as well as by the total population.

1Vila, Kaplan, et al. Kidney Int. 2004; 65(5): 1761-1773.
2Cuadros, Trilla, et al. Eur J Cancer. 2013; 49 (8): 2014-2047.

About CDX‑014
CDX-014 is a fully human monoclonal antibody-drug conjugate (ADC) that targets T-cell immunoglobulin mucin-1 (TIM-1). TIM-1 expression is upregulated in several cancers, most notably renal cell and ovarian carcinomas, and has very restricted expression in healthy tissue. The TIM-1-targeting antibody, CR014, is linked to a potent cytotoxic, monomethyl auristatin E (MMAE), using Seattle Genetics’ proprietary technology. CDX-014 is designed to be stable in the bloodstream, but to release MMAE upon internalization into TIM-1-expressing tumor cells, resulting in a targeted cell-killing effect. CDX-014 is in development for the treatment of advanced/metastatic clear cell or papillary renal cell carcinoma.

AbbVie Receives U.S. FDA Rare Pediatric Disease Designation for Investigational ABT-414 for the Treatment of a Type of Pediatric Brain Tumor known as Diffuse Intrinsic Pontine Glioma (DIPG)

On July 11, 2016 AbbVie (NYSE: ABBV), a global biopharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) granted Rare Pediatric Disease Designation for ABT-414, an investigational antibody drug conjugate (ADC) targeting the epidermal growth factor receptor (EGFR), for the treatment of pediatric patients with EGFR-amplified Diffuse Intrinsic Pontine Glioma (DIPG), known to be highly aggressive and difficult to treat brain tumors found at the base of the brain (Press release, AbbVie, JUL 11, 2016, View Source [SID:1234513814]).1

Though brainstem tumors are extremely rare among adults, they comprise approximately 10-15 percent of all pediatric brain tumors. DIPG is the most common subtype of tumor in this anatomical region and the second most common malignant brain tumor of childhood, with an estimated 200-400 children affected each year in the United States.2,3,8

The FDA granted the Rare Pediatric Disease Designation based on a proposed pediatric sub-study "nested" within the ongoing Phase 2 study of ABT-414 in adults with recurrent EGFR-amplified glioblastoma, conducted in collaboration with the European Organization for Research and Treatment of Cancer (EORTC).4,5

"Pediatric patients with high grade gliomas have a rare and fatal disease.2 This Rare Pediatric Designation, a first for AbbVie, is an important advancement as we continue to evaluate ABT-414 and its potential to help this group of patients who desperately need a new treatment option," said Gary Gordon, M.D., vice president, oncology clinical development, AbbVie. "The proposal of including a nested cohort within an adult global trial is an endeavor that we hope may bring more treatments to pediatric patients."

About ABT-414
ABT-414 is an investigational monoclonal antibody drug conjugate (ADC) targeting the epidermal growth factor receptor (EGFR) developed by AbbVie researchers with components in-licensed from Life Science Pharmaceuticals, Inc. and Seattle Genetics.6 AbbVie is evaluating it for the treatment of adult patients with EGFR-amplified glioblastoma, an aggressive malignant primary brain tumor.6,7 In 2014, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency granted Orphan Drug Designation for the treatment of adult glioblastoma and glioma, respectively.4,5 In 2016, the FDA granted Rare Disease Designation to ABT-414 for the treatment of pediatric patients with EGFR-amplified Diffuse Intrinsic Pontine Gliomas (DIPG). ABT-414 is an investigational compound and its efficacy and safety have not been established by the FDA or any other health authority.

About Pediatric High Grade Gliomas
Diffuse Intrinsic Pontine Glioma (DIPG) is a type of high grade glioma (HGG).8 HGG represents one of the most common central nervous system (CNS) tumors among adults; however, they comprise only approximately 8-12 percent of all CNS tumors in pediatric patients.2 Pediatric HGG are highly aggressive tumors that account for a significant amount of morbidity and mortality among children.2 Despite numerous treatment approaches, five-year survival outcomes range from 15-35 percent and the majority of children succumb to their disease.2,9

About Glioblastoma
Glioblastoma is the most common and most aggressive type of malignant primary brain tumor.7 Prior to diagnosis, patients may experience headache, vision problems, nausea/vomiting, personality changes and seizures.7 For adults with more aggressive glioblastoma, treated with concurrent Temozolamide and radiation therapy, median survival is about 14.6 months.9 Treatment for glioblastoma remains challenging.7 Standard treatment is surgical resection, radiotherapy and concomitant adjunctive chemotherapy.9

Sorrento and Servier Enter Into Exclusive Worldwide License and Collaboration Agreement for Development and Commercialization of Anti-PD-1 Antibody

On July 11, 2016 Sorrento Therapeutics, Inc. (NASDAQ: SRNE, "Sorrento"), an antibody-centric, clinical-stage biopharmaceutical company developing new treatments for cancer and other unmet medical needs, and Servier, the largest non-listed pharmaceutical company in France, reported a license and collaboration agreement for the development, manufacture and commercialization of products using Sorrento’s fully human immuno-oncology anti-PD-1 monoclonal antibody (mAb) STI-A1110 (Press release, Sorrento Therapeutics, JUL 11, 2016, View Source [SID:1234513813]).

Sorrento’s proprietary G-MAB library platform was used to identify and generate STI-A1110, which targets PD-1, one of the key targets in the rapidly developing immuno-oncology therapy market. The agreement provides Servier with an exclusive worldwide license to Sorrento’s STI-A1110 mAb asset, covering all indications including hematological and solid tumor cancers. Servier also obtains full rights to develop, register and commercialize the products and will bear all costs for these activities.

The financial terms of the agreement include, among other things, a non-refundable upfront payment to Sorrento of €25 million. Sorrento may also receive development milestone payments for the initial product and each additional product. Sorrento may receive up to €710 million in various payments based on commercial sales milestones related to annual net sales levels for the initial product and then also for each additional product. In addition to the commercial sales milestones, Sorrento will be entitled to receive variable royalties on the sales of all commercialized products ranging from high single-digit to double-digit percentages.

"We are excited about partnering on our anti-PD-1 immune checkpoint antibody with Servier, which is recognized for its scientific excellency and as a pioneer in CAR-T therapies. This agreement represents validation for Sorrento’s antibody technologies and R&D capabilities," stated Dr. Henry Ji, President and CEO of Sorrento. "This also further establishes Sorrento as a notable immuno-oncology company with a comprehensive portfolio of clinical stage and preclinical immunotherapies. We look forward to working closely with the Servier team and growing this global partnership."

"We have tested STI-A1110 in preclinical studies conducted at Servier and we believe that, used in combination with several products from our portfolio, it will lead to the development of new treatments for hematological as well as solid tumor cancers," added Dr. Jean-Pierre Abastado, Director of the Oncology Innovation Therapeutic Pole for Servier.

PIERIS PHARMACEUTICALS ANNOUNCES PRESENTATION OF DATA FOR ITS LEAD IO BISPECIFIC PROGRAM, PRS-343, AT THE 2016 CRI-CIMT-EATI-AACR INTERNATIONAL CANCER IMMUNOTHERAPY CONFERENCE

On July 9, 2016 Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for cancer and other diseases reported that it will be presenting a poster at the 2016 CRI-CIMT-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) -Translating Science into Survival, taking place in New York City, September 25-26, 2016 (Press release, Pieris Pharmaceuticals, JUL 9, 2016, View Source [SID:1234515005]).

The poster entitled "Costimulatory T-cell engagement by PRS-343, a CD137 (4-1BB)/HER2 bispecific, leads to tumor growth inhibition and TIL expansion in humanized mouse model," will be presented on September 26, 2016.

Session Title: Poster Session
Session Subtitle: New Agents and Their Mode of Action in Animals and Humans
Poster Number: B016
Session Date: Monday, September 26, 2016
Presentation Time: 5:15 p.m. to 7:45 p.m. ET
Session Location: New York Hilton Midtown – Grand America Hall I

About PRS-343
PRS-343 is a bispecific monoclonal antibody/Anticalin fusion protein comprised of a HER2 tumor-targeting mAb genetically linked to a potent anticalin specific for the immune costimulatory TNF family receptor 4-1BB (CD137). PRS-343 is being developed as the first 4-1BB based therapeutic to mediate the activation of tumor-specific T lymphocytes selectively within the Tumor Micro-Environment (TME). 4-1BB is an established marker for tumor-specific infiltrating T lymphocytes (TILs) and is, therefore, an attractive target for cancer immunotherapy. In in vivo preclinical tumor models, PRS-343 has demonstrated potent T lymphocyte activation localized to the TME of established HER2-positive tumors, indicating the potential for both enhanced safety and efficacy.