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TRACON Pharmaceuticals Announces Completion of Enrollment in Randomized Phase 2b TRAXAR Study of TRC105 and Inlyta® in Renal Cell Carcinoma

On September 7, 2017 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age-related macular degeneration and fibrotic diseases, reported that it has completed enrollment in the randomized Phase 2b TRAXAR study of TRC105 and Inlyta (axitinib) in patients with advanced or metastatic renal cell carcinoma (RCC) (Press release, Tracon Pharmaceuticals, SEP 7, 2017, View Source [SID1234520430]).

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TRACON expects to report top-line progression-free survival (PFS) data from the study later this year, with the exact timing driven by the number of progression events or deaths (from any cause) that define PFS. The study is expected to yield between 80 and 110 events as confirmed by the study’s independent central review committee at the time of data readout, which is expected to provide between 70% and 80% power to detect an improvement in PFS from 4.8 months with Inlyta to 7.2 months with the combination of TRC105 and Inlyta. PFS will also be assessed in patients with predefined levels of two soluble biomarkers that correlated with response in the Phase 1b portion of the trial, osteopontin and TGF-β receptor III.

"The completion of enrollment in the TRAXAR study represents an important step in the development of TRC105 and keeps us on track to deliver top-line data later this year," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "The TRAXAR study provides a strong example of the depth of the TRACON product development platform as we have efficiently conducted the study at more than 50 sites located in Europe and the United States."

About the TRAXAR Phase 2b Clinical Trial in RCC

The Phase 2b TRAXAR clinical trial is a multicenter, open-label, randomized clinical trial of TRC105 in combination with Inlyta versus Inlyta alone in patients with advanced or metastatic RCC. The primary endpoint of the Phase 2b study is progression-free survival and the trial enrolled 150 patients who failed one prior VEGF inhibitor in the study. Patients may have also failed one prior mTOR inhibitor and one prior immunotherapy. For additional information on this clinical trial, please visit www.clinicaltrials.gov, identifier NCT01806064.

About TRC105 (carotuximab)

TRC105 is a novel, clinical stage antibody to endoglin, a protein overexpressed on proliferating endothelial cells that is essential for angiogenesis, the process of new blood vessel formation. TRC105 is currently being studied in one Phase 3 and multiple Phase 2 clinical trials sponsored by TRACON or the National Cancer Institute for the treatment of solid tumors in combination with VEGF inhibitors. TRC105 has received orphan designation for the treatment of soft tissue sarcoma in both the U.S. and EU. The ophthalmic formulation of TRC105, DE-122, is currently in a Phase 2 trial for patients with wet AMD. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical_trials.php.

Transgene and Institut Bergonié Present a Poster on the METROmaJX Trial (Oncolytic Virus Pexa-Vec + Metronomic Cyclophosphamide) at ESMO 2017 Congress

On September 7, 2017 Transgene (Paris:TNG) (Euronext Paris: TNG), a biotech company that designs and develops viral-based immunotherapies, reported that the results of the Phase 1 part of the METROmaJX trial will be presented in a poster presentation at the annual congress of European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) (8-12 September 2017, Madrid, Spain) (Press release, Transgene, SEP 7, 2017, View Source [SID1234520416]). These Phase 1 trial results showed that the regimen associating intravenous infusion of Pexa-Vec (JX-594) with low-dose cyclophosphamide was well-tolerated with no dose limiting toxicity in patients with solid tumors. Following these positive results, the Phase 2 part of the trial is currently enrolling patients with soft tissue sarcoma (STS) and HER2 negative-breast cancer.

Abstract title: A phase Ib trial of JX-594 (Pexa-Vec), a targeted multimechanistic oncolytic vaccinia virus, in combination with low-dose cyclophosphamide in patients with advanced solid tumors

Poster number: 414P
Date and time: 11 September 2017, 1:15 pm
Location: Hall 8
Presenter: Pr Antoine Italiano, MD, PhD (Institut Bergonié)
The abstract can be downloaded from the ESMO (Free ESMO Whitepaper) website and from Transgene’s website (www.transgene.fr).

METROmaJX is a Phase 1/2 clinical trial evaluating the tolerability and efficacy of the co-administration of Pexa-Vec with metronomic cyclophosphamide (low doses given with high frequency) in patients with advanced solid tumors (NCT02630368).

The Phase 2 stage of the trial is currently enrolling patients with STS and HER2 negative-breast cancer. It will primarily assess the anti-tumor efficacy of this novel combination regimen.

Prof. Antoine Italiano is the principal investigator of the trial. Institut Bergonié is the sponsor of this trial, that is supported by INCa (French National Cancer Institute) within the frame of the CLIP² projects.

Pexa-Vec is a GM-CSF expressing vaccinia derived oncolytic virus. Cyclophosphamide is a chemotherapy. Metronomic administration involves giving low doses of the drug at a higher frequency and is known to have an immunomodulating activity. The combination of Pexa-Vec and cyclophosphamide aims at targeting two distinct steps in the immune response against cancer cells and has the potential to be significantly more effective than either product alone.

Regeneron and Sanofi Announce Cemiplimab (REGN2810) Has Received FDA Breakthrough Therapy Designation for Advanced Cutaneous Squamous Cell Carcinoma

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]).

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.

Peregrine Pharmaceuticals Announces First Patient Dosed in Phase II Clinical Trial Evaluating Bavituximab Treatment Combination in Patients with Newly Diagnosed Glioblastoma

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.

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.

Updated Data for Indoximod Plus KEYTRUDA® (pembrolizumab) Demonstrate Improvement of Response Rate for Patients with Advanced Melanoma

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.

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.