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Clinical Trial to Evaluate Two Biothera Cancer Drugs for Advanced Pancreatic Cancer

On October 23, 2014 Biothera reported that a phase 1b clinical trial at the University of Illinois at Chicago (UIC) will evaluate a new combination therapy for advanced pancreatic cancer that includes two Biothera cancer immunotherapy drug candidates (Press release Biothera, OCT 23, 2014, View Source [SID:1234500878]).

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The investigator-sponsored study combines Biothera’s Imprime PGG and mucin-1 (MUC1) targeted monoclonal antibody BTH1704 with the chemotherapy gemcitabine (Gemzar) in patients with advanced, previously treated pancreatic ductal adenocarcinoma (PDAC).

"There is an urgent and unmet need for effective treatments for patients with advanced pancreatic cancer after first-line chemotherapy fails," said Dr. Neeta Venepalli, UIC assistant professor of hematology/oncology and principal investigator of the study.

Advanced PDAC has a five-year survival rate of less than 5% and is the fourth-leading cause of cancer deaths in the U.S., claiming nearly 40,000 lives each year.

Mucin-1 (CD 227) is a tumor-associated antigen that is both overexpressed and aberrantly glycosylated in more than 60% of pancreatic cancers, and has been associated with poor clinical outcomes and resistance to chemotherapy. BTH1704 is a monoclonal antibody that binds to Mucin-1 on the surface of pancreas cancer cells, resulting in opsonization of the tumor cells, effectively marking them for destruction by innate immune cells.

Imprime PGG is a biologic immune modulator that targets the innate immune system, enabling neutrophils via a complement receptor 3 (CR3)-dependent mechanism to exert anti-tumor activity against complement opsonized tumor cells. This novel mechanism synergizes with anti-tumor monoclonal antibodies, with significant therapeutic potential in a wide range of cancer indications.

"We are excited to see two promising Biothera products advance into clinical development in pancreas cancer – an area of particularly high unmet medical need," said Ada Braun, M.D., Ph.D., Biothera’s chief medical officer. "This study is designed to provide important safety and translational research information as well as proof of concept efficacy data for this innovative combination therapy approach."

Phil L’Huillier, director of business development for Cancer Research Technology, which exclusively licenses BTH1704 to Biothera, said: "Recent research has highlighted the potential to treat cancer by combining immunotherapies with other targeted treatments and we welcome the opportunity to collaborate with companies working in this promising area of research."

Study Design
This phase 1b open-label dose escalation study will evaluate weekly treatment with BTH1704 at assigned doses (3, 6 or 9 mg/kg) and Imprime PGG 4 mg/kg, in combination with gemcitabine 1000 mg/m2 administered on days 1, 8, and 15 of each 28-day cycle, in up to 24 patients with locally advanced, recurrent or metastatic PDAC. The primary objective of the study is to determine the maximum administered dose of BTH1704 in combination with gemcitabine and Imprime PGG when given to patients with advanced and previously treated PDAC. Secondary objectives are to evaluate clinical response, time to progression, progression-free survival and overall survival. For more information on this trial, please visit View Source using the identifier NCT 02132403.

Medivation Inc. Licenses Clinical Stage Anti-PD-1 Immune Modulatory Monoclonal Antibody From CureTech Ltd. for Potential Applications in Oncology

On October 23, 2014 Medivation and CureTech reported that Medivation has licensed exclusive worldwide rights to CureTech’s late-stage clinical molecule pidilizumab (CT-011), an immune modulatory anti-PD-1 monoclonal antibody (Press release Medivation, OCT 23, 2014, View Source [SID:1234500873]). Under the license agreement, Medivation will be responsible for all development, regulatory and commercialization activities for pidilizumab for all indications, including oncology.

"Immuno-oncology is a significant area of interest for researchers in the development of anti-cancer therapies, marked by its potential to stimulate the body’s immune system to fight disease," said David Hung, M.D., President and Chief Executive Officer of Medivation. "Licensing rights to pidilizumab under this agreement marks an important step in our strategy to further diversify our portfolio."

"We believe that Medivation’s expertise and accomplishments in drug development will be a tremendous advantage in the highly competitive field of oncology immunotherapy," said Michael Schickler, Chief Executive Officer of CureTech. "We are pleased that Medivation will advance this molecule to the next stage of development and potential commercialization."

The arrangement with CureTech also includes a manufacturing and supply agreement, under which CureTech will manufacture and supply the antibody to Medivation over the next 3 years for clinical development purposes. In addition, the arrangement contemplates a guaranty agreement between Medivation and CureTech’s largest (53%) shareholder — Clal Biotechnology Industries Ltd. (CBI) — with respect to certain obligations of CureTech. The guaranty is subject to approval by CBI shareholders. If approval of the guaranty agreement is not obtained, Medivation has the option to terminate both the license agreement and the manufacturing and supply agreement or proceed with such agreements on reduced economic terms (i.e. a reduction of $2 million in the upfront payment and 1% from each tier of royalties). The shareholder vote on the guaranty and Medivation’s exercise of its option to continue to maintain the license are expected to occur in December 2014.

Under the terms of the license agreement, and depending on whether the guaranty from CBI is obtained, CureTech would receive an upfront payment of up to $5.0 million from Medivation and would also be entitled to payments upon the attainment of certain development and regulatory milestones totaling $85 million. In addition, CureTech would be eligible to receive sales based milestone payments totaling up to $245 million, upon the achievement of certain annual worldwide net sales thresholds, and tiered royalties ranging from 4%-11% based on annual worldwide net sales.

Clovis Oncology Announces First Patient Enrolled in Lucitanib Phase 2 Study in Squamous Non-small Cell Lung Cancer

On October 23, 2014 Clovis Oncology reported that its global Phase 2 study of lucitanib in patients with FGFR1-amplified squamous non-small cell lung cancer (NSCLC) has commenced and the first patient has been dosed at a U.S. study site (Press release Clovis Oncology, OCT 23, 2014, View Source;p=RssLanding&cat=news&id=1981074 [SID:1234500872]). Lucitanib is the Company’s oral, potent inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors 1 through 3 (FGFR1-3), vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3) and platelet-derived growth factor receptors alpha and beta (PDGFR α-ß).

"The lucitanib data presented to date in patients with FGF-aberrant breast cancer are very encouraging, and we know that FGFR1 amplification occurs in approximately 15 percent of patients with squamous non-small cell lung cancer," said Dr. Benjamin Besse, Head of Thoracic Oncology, Institut Gustave Roussy, and the lead investigator of the study in squamous NSCLC. "Accordingly, we are very enthusiastic to explore lucitanib in this selected population of patients with lung cancer, for whom there is significant need for novel therapies."

"Less than a year after acquiring lucitanib, we are commencing a broad clinical development program, which includes this study in FGFR1-amplified squamous NSCLC, as well as our ongoing study currently underway in FGF-aberrant breast cancer," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We are enthusiastic about the opportunity to explore lucitanib in these indications, and potentially in other solid tumors exhibiting FGFR pathway activation."

The Phase 2 study will enroll FGFR1-amplified squamous NSCLC patients with advanced disease who have progressed on at least one prior line of therapy. The global study will assess objective response rate, progression-free survival, and duration of response, as well as the safety, tolerability, and pharmacokinetics of lucitanib.

Lucitanib is unique among tyrosine kinase inhibitors being developed for cancer therapy, as it effectively targets fibroblast growth factor receptors (FGFR)1-3, vascular endothelial growth factor receptors (VEGFR)1-3, and platelet-derived growth factor receptors (PDGFR) alpha and beta with minimal off-target activity. This selectivity profile allows lucitanib to provide a potential benefit to cancer patients by targeting multiple pathways of tumor development. Specifically, by targeting the FGFR pathway, lucitanib can have a direct antitumor effect in FGF/FGFR driven tumors such as breast or lung cancers harboring amplification of the FGFR1 gene. In addition, by targeting the FGFR, VEGFR and PDGFR receptors lucitanib also can inhibit the development of blood vessels that are required by the tumor to grow and spread.

In addition to this Clovis-sponsored Phase 2 study in squamous NSCLC, a global development program for lucitanib in breast cancer is underway, which includes the Clovis-sponsored Phase 2 study in FGF-aberrant advanced breast cancer being conducted in the U.S., the Servier-sponsored FINESSE study of lucitanib monotherapy being conducted in Europe, Canada and Australia as well as the Servier-sponsored INES study evaluating lucitanib in combination with fulvestrant after failure of endocrine therapy.

Aduro Presents Updated Interim Results from Phase 1b Clinical Trial in Mesothelioma at International Mesothelioma Interest Group Conference

On October 23, 2014 Aduro BioTech reported the presentation of updated safety and efficacy data from an ongoing Phase 1b clinical trial of its novel immunotherapy CRS-207 in combination with standard chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM) (Press release Aduro BioTech, OCT 23, 2014, View Source [SID:1234500871]). Of 16 evaluable patients with response data, 75% (12/16) had confirmed durable partial responses (PR) and 19% (3/16) experienced stable disease (SD) after CRS-207 and chemotherapy, for a 94% rate of disease control (PR and SD). At the time of the presentation, estimated progression-free survival was 7.5 months with one patient on study for more than 19 months, currently receiving maintenance therapy with CRS-207 following the combination treatment.

The results were presented by Raffit Hassan, M.D., winner of the 2014 Wagner Medal for his career work in mesothelioma and co-chief of the Thoracic and GI Oncology Branch at the National Cancer Institute, in an oral presentation at the International Mesothelioma Interest Group (iMig) Conference held in Cape Town, South Africa. CRS-207, based on Aduro’s live-attenuated, double-deleted (LADD) Listeria monocytogenes immunotherapy platform, has been engineered to induce a potent innate immune response as well as an adaptive immune response targeting mesothelin, an antigen over-expressed in MPM tumors.

"We continue to be excited by the results from this trial of our novel immunotherapy in combination with chemotherapy in this difficult-to-treat patient population," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "While the findings warrant further investigation, we believe CRS-207 may prove to be a very attractive therapeutic option in the armamentarium to improve overall response rates and boost the duration of those responses."

Dirk G. Brockstedt, Ph.D., senior vice president of research and development at Aduro, added, "These results continue to support the promise of our technology as a method to boost and rally a patient’s immune system to target tumors. We plan to further evaluate CRS-207 in combination with chemotherapy in a randomized, controlled Phase 2 clinical trial in mesothelioma, which we anticipate to begin in the first half of 2015."

The multi-center Phase 1b study is open to patients with unresectable MPM who are chemotherapy-naïve, have good performance status (ECOG 0 or 1) and adequate organ function. Under the trial design, eligible patients receive two prime vaccinations with CRS-207 two weeks apart, followed by up to six cycles of standard of care pemetrexed and cisplatin chemotherapy three weeks apart and then two CRS-207 boost vaccinations three weeks apart. Clinically stable patients are eligible to receive CRS-207 maintenance vaccinations every eight weeks. Subjects are followed every eight weeks until disease progression. Objectives of the study are to assess safety, immunogenicity, objective tumor responses and tumor marker kinetics. Twenty-three patients have been enrolled thus far and additional response, follow-up and immune response data are pending.

At the time of the presentation, the median time on study was 229 days (range: 155-570 days). No treatment-related serious adverse events or unexpected toxicities were observed. The most common adverse events associated with CRS-207 were infusion-related chills and fever, which were transient, mild and self-limiting.

Pfizer Wins SUTENT® Patent Case In Delaware District Court

On October 23, 2014 Pfizer reported that the U.S. District Court for the District of Delaware upheld its basic patent and the L-malate salt patent covering SUTENT (sunitinib malate) capsules (Press release Pfizer, OCT 23, 2014, http://www.pfizer.com/news/press-release/press-release-detail/pfizer_wins_sutent_patent_case_in_delaware_district_court [SID:1234500866]). This decision, which is subject to appeal, affirms Pfizer’s right to exclusively provide sunitinib malate as SUTENT to patients through the term of the patent, which expires in 2021.

"The Court’s decision acknowledges the validity and infringement of our patents and affirms the value of SUTENT, a standard of care in the treatment of advanced renal cell carcinoma," said Douglas M. Lankler, executive vice president and general counsel for Pfizer. "Defending our intellectual property is crucial to our ability to discover and develop innovative new medicines, which is at the very core of what we do."

Pfizer filed suit in June 2010 after Mylan Pharmaceuticals Inc. applied to the U.S. Food and Drug Administration (FDA) to market a generic version of SUTENT prior to the expiration of the patents covering sunitinib malate and its uses. After a four-day trial, the Court agreed that Mylan infringed the valid patents covering SUTENT.

The patents at issue are U.S. Patent Nos.6,573,293 and 7,125,905.