On September 8, 2017 /PRNewswire/ — Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation status to cemiplimab (REGN2810) for the treatment of adults with metastatic cutaneous squamous cell carcinoma (CSCC) and adults with locally advanced and unresectable CSCC, the second deadliest skin cancer after melanoma. Cemiplimab is an investigational human, monoclonal antibody targeting PD-1 (Press release, Regeneron, SEP 8, 2017, View Source [SID1234520414]).

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Regeneron and Sanofi previously reported positive, preliminary results for cemiplimab from two expansion cohorts involving 26 advanced CSCC patients in a Phase 1 study of nearly 400 patients, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2017. EMPOWER-CSCC 1, a Phase 2, potentially pivotal, single-arm, open-label clinical trial of cemiplimab is currently enrolling patients with metastatic CSCC and locally advanced and unresectable CSCC. Cemiplimab was discovered using Regeneron’s proprietary VelocImmune technology that yields optimized fully-human antibodies, and is being jointly developed by Regeneron and Sanofi under a global collaboration agreement. Pending data results, the companies anticipate submitting a biologics license application for cemiplimab with the FDA in the first quarter of 2018.

CSCC is the second most common type of skin cancer in the United States. Although CSCC has a good prognosis when caught early, it can prove especially difficult to treat when it progresses to advanced stages. Patients at this stage can be disfigured due to multiple surgeries to remove CSCC tumors on the head, neck and other parts of the body.1 CSCC is responsible for the most deaths among non-melanoma skin cancer patients.

Breakthrough Therapy designation serves to expedite the development and review of drugs that target serious or life- threatening conditions. Drugs qualifying for this designation must show credible evidence of a substantial improvement on a clinically significant endpoint over available therapies, or over placebo if there is no available therapy. The designation includes all of the Fast Track program features, as well as more intensive FDA guidance and discussion. The Breakthrough Therapy designation is distinct from both accelerated approval and priority review, which can also be granted to the same drug if relevant criteria are met.

Cemiplimab is currently under clinical development, and its safety and efficacy has not been fully evaluated by any regulatory authority.

On September 07, 2017 (GLOBE NEWSWIRE) — 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 dosing of the first patient in a Phase II clinical trial evaluating the combination of bavituximab, temozolomide, and radiation therapy in patients with newly diagnosed glioblastoma (Press release, Peregrine Pharmaceuticals, SEP 7, 2017, View Source [SID1234520413]). Elizabeth R. Gerstner, MD, at Massachusetts General Hospital Cancer Center, is the primary investigator for the trial, which is one of three bavituximab clinical studies being funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program (ORP) through a grant provided by Peregrine.

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The single group, interventional Phase II trial will enroll approximately 36 patients with newly diagnosed glioblastoma. Patients will receive standard of care radiation, as well as daily temozolomide treatment and weekly bavituximab treatment, throughout the 18-week study. The primary objective of the trial is overall survival at twelve months. Secondary outcome measures include progression free survival (PFS) and radiographic response.

"We are hopeful that results from this trial, as well as from the two additional studies at NCCN Member Institutions, will continue to support our belief that bavituximab works to create a more immune active tumor microenvironment in which other therapies are able to have a greater anti-tumor effect," said Joseph Shan, MPH, vice president, clinical and regulatory affairs of Peregrine. "We look forward to following this important study at the Massachusetts General Hospital Cancer Center, as well as the planned trials at the Moffitt Cancer Center and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins."

Results from a previous preclinical study highlighted that PS-targeting antibodies similar to bavituximab synergize with radiation to improve anti-tumor activity in the F98 rat model of glioblastoma. These study data, generated by researchers at the University of Texas, Southwestern, demonstrated that PS-targeting treatment in combination with radiation more than doubled the median survival time of glioma-bearing rats and was significantly superior to either PS-targeting or radiation alone (p < 0.001). Additionally, 13% of the glioma-bearing rats treated with the combination were rendered disease free. These disease-free animals were immune to a rechallenge with F98 glioma cells, suggesting that the combination treatment had induced an adaptive immunity to the tumor cells.

NCCN, a not-for-profit alliance of 27 leading cancer centers devoted to patient care, research, and education, is dedicated to improving the quality, effectiveness, and efficiency of cancer care so that patients can live better lives. Funding for the three investigator-initiated clinical studies has been provided by Peregrine in the form of a research grant to NCCN ORP. NCCN is responsible for oversight and monitoring of the clinical studies through the research grant.

Details of the two additional NCCN-supported studies are as follows:

A Phase I Trial of Sorafenib and Bavituximab Plus Stereotactic Body Radiation Therapy (SBRT) for 1st Line Treatment of Unresectable Hepatocellular Carcinoma; Jessica Frakes, MD, Moffitt Cancer Center.

Phase II Study of Pembrolizumab and Bavituximab for Progressive Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck; Ranee Mehra, MD, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

Bavituximab is an investigational immune-modulatory monoclonal antibody that targets phosphatidylserine (PS), a phospholipid that inhibits the ability of immune cells to recognize and fight tumors. Bavituximab is believed to reverse PS-mediated immunosuppression 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. This mechanism may play an important role in allowing other cancer therapies to more effectively attack tumors by reversing the immunosuppression that limits the impact of those treatments.

Importantly, bavituximab has also demonstrated a favorable safety and tolerability profile across several clinical trials conducted to date, which may offer the compound a key advantage as the evolving cancer treatment landscape continues to shift to a combination therapy approach. The ability to be added to a range of other cancer therapies without causing added safety concerns may position bavituximab favorably as a component of combination treatments.

On September 7, 2017 NewLink Genetics Corporation (NASDAQ: NLNK) reported updated data from the ongoing Phase 2 NLG2103 study of indoximod, NewLink Genetics’ IDO pathway inhibitor, in combination with the PD-1 pathway inhibitor, KEYTRUDA (pembrolizumab) (Press release, NewLink Genetics, SEP 7, 2017, View Source [SID1234520412]). These data will be highlighted in an oral presentation at the Third International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) in Frankfurt/Mainz, Germany, on September 9, 2017 by Yousef Zakharia, M.D., Assistant Professor of Medicine, Division of Hematology, Oncology and Blood & Marrow Transplantation at the University of Iowa and Holden Comprehensive Cancer Center.

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The presentation entitled, "Combined Inhibition of the IDO and PD-1 Pathways Improves the Response Rate for Patients with Advanced Melanoma", showed an improvement over previously reported results presented at the AACR (Free AACR Whitepaper) Annual Meeting 2017 for both the Complete Response rate (CR) and the Overall Response Rate (ORR) for patients1 who received indoximod plus pembrolizumab. Evaluable patients were defined as those having at least one on-treatment imaging study.

Key findings in the updated data reported today:

Improvement in Complete Response (CR) to 20% (10/51 patients) compared to CR of 12% (6/51 patients)
The Progression-Free Survival (PFS) by RECIST criteria was 56% at one year with median PFS (mPFS) of 12.9 months
"We are encouraged by the progression-free survival and the improvement in complete responses observed in the trial," said Charles J. Link, Jr., M.D., Chairman, Chief Executive Officer, and Chief Scientific Officer. "The updated data further support our decision to initiate a pivotal trial for patients with advanced melanoma."

Indoximod plus Pembrolizumab Data from Phase 2 Trial in Advanced Melanoma
n1 = 51 patients n (%)
ORR 31 (61)
CR 10 (20)
PR 21 (41)
SD 10 (20)
DCR 41 (80)
PD 10 (20)
mPFS (months) 12.9
PFS at 12 months 56%
overall response rate (ORR), complete response (CR), partial response (PR), stable disease (SD), disease control
rate (DCR), progressive disease (PD), median progression-free survival (mPFS), progression-free survival (PFS)
1 Update includes only those patients with cutaneous, mucosal and melanoma of unknown primary origin.
Data as presented at Third International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper)
Indoximod in combination with pembrolizumab was well-tolerated. The most common all-grade adverse events were fatigue, headache, and nausea. Three patients experienced grade 3 serious adverse events (SAE) possibly attributed to indoximod. Three patients experienced SAEs that led to discontinuation of treatment. There were no treatment related deaths.

Pivotal Trial of Indoximod in Advanced Melanoma to Include Both PD-1 Inhibitors, KEYTRUDA (pembrolizumab) and OPDIVO (nivolumab)

The pivotal trial has been designed as a large-scale (600 patients) trial in Stage III unresectable and metastatic stage IV melanoma. The trial will have a one to one randomization between indoximod plus KEYTRUDA (pembrolizumab) or OPDIVO (nivolumab) compared to single agent PD-1 inhibitor. The co-primary endpoints of the study are PFS by RECIST criteria and Overall Survival (OS).

"Our team is excited to move forward with this pivotal trial," said Eugene Kennedy, M.D., Vice President of Clinical and Medical Affairs. "We believe that allowing physicians the choice of either pembrolizumab or nivolumab accurately reflects current clinical care and should aid in enrolling the trial by the end of 2018."

About Indoximod

Indoximod is an investigational, orally available small molecule targeting the IDO pathway. The IDO pathway is one of the key immuno-oncology targets involved in regulating the tumor microenvironment and immune escape.

NewLink Genetics is currently evaluating indoximod in multiple combination studies for patients with various types of cancer including melanoma, acute myeloid leukemia, pancreatic cancer and prostate cancer.

On September 7, 2017 Kura Oncology, Inc., (Nasdaq:KURA) a clinical stage biopharmaceutical company focused on the development of precision medicines for oncology, reported positive topline results from a Phase 2 trial for its lead product candidate, tipifarnib, in patients with HRAS mutant relapsed or refractory squamous cell carcinomas of the head and neck (HNSCC) (Press release, Kura Oncology, SEP 7, 2017, View Source [SID1234520411]). The Phase 2 trial achieved its primary endpoint prior to the completion of enrollment.

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The trial protocol requires four confirmed, partial responses, per RECIST 1.1 criteria, out of 18 patients to meet its primary endpoint. Four confirmed, partial responses and two patients with disease stabilization have been observed among the first six evaluable HNSCC patients enrolled in the trial. In addition, objective responses greater than one year in duration have already been observed in two patients. All patients joined the study upon progression on prior therapy, including chemotherapy, cetuximab or immune therapy. Kura will continue to enroll HRAS mutant HNSCC patients and plans to present data from the study at an upcoming scientific or medical conference.

"We have observed rapid and, in some cases, dramatic responses in patients with relapsed and/or refractory HNSCC who do not appear to benefit from other therapies," said Antonio Gualberto, M.D., Ph.D., Chief Medical Officer of Kura Oncology. "Based on these very encouraging results, we are exploring available options to advance the development of tipifarnib in this patient population as quickly as possible."

About HRAS Mutant HNSCC

Head and neck cancer is one of the leading causes of cancer-related deaths worldwide, with squamous cell carcinomas accounting for most head and neck cancers. Response rates for the three agents approved for treatment of HNSCC in the second line, including cetuximab and immune therapy agents, are in the range of 13-16%, and median overall survival is up to 7.5 months. HRAS is a proto-oncogene that has been implicated in the development and progression of HNSCC and has been established to be uniquely farnesylated.

On September 7, 2017 Iovance Biotherapeutics, Inc. (NASDAQ:IOVA), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported that it has entered into a preclinical research collaboration with The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) focused on TIL, marrow-infiltrating lymphocyte (MIL) and peripheral blood-associated lymphocyte technologies (Press release, Iovance Biotherapeutics, SEP 7, 2017, View Source [SID1234520410]).

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The collaboration will initially focus on hematologic malignancies in areas of poor prognostic cancers with high unmet medical need, which include acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). The collaboration will be co-led by Iovance researchers and by Dr. John Byrd, D. Warren Brown Chair of Leukemia Research, Distinguished University Professor of Medicine, Medicinal Chemistry and Veterinary Biosciences at the OSUCCC – James.

"We are very pleased to collaborate with the OSUCCC – James and Dr. Byrd, who brings an impressive track record and expertise in the preclinical and clinical development of ground-breaking hematological therapies," said Maria Fardis, Ph.D., MBA, President and Chief Executive Officer of Iovance Biotherapeutics. "Our initial internal work in developing TIL in hematologic malignancies will be presented at the upcoming ESMO (Free ESMO Whitepaper) 2017 Congress and that work, along with our collaboration with the OSUCCC – James, shows our continued efforts in exploring the utilization of TIL therapy in hematological oncology indications, in addition to our ongoing clinical work in solid tumor indications."

"TIL directed therapy is an exciting novel application to both AML and CLL and our research team at the OSUCCC – James is excited to be part of this collaborative research to explore this new treatment approach," said Dr. Byrd.