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NewLink Genetics Corporation Presents Preliminary Safety Data From Randomized Phase 2 Trial of Indoximod, an IDO Pathway Inhibitor, at San Antonio Breast Cancer Symposium

AMES, Iowa and SAN ANTONIO, Dec. 10, 2015 (GLOBE NEWSWIRE) -- NewLink Genetics Corporation (NASDAQ:NLNK), a biopharmaceutical company at the forefront of discovering, developing and commercializing novel immuno-oncology product candidates, including both cellular immunotherapy and checkpoint inhibitor platforms, to improve the lives of patients with cancer, today announced the presentation of preliminary safety data from NLG2101, a randomized Phase 2 trial evaluating an IDO pathway inhibitor indoximod in combination with taxane-based chemotherapy for patients with breast cancer. The data were presented today at the 2015 San Antonio Breast Cancer Symposium.

NLG2101 is a randomized, double-blind, placebo-controlled Phase 2 trial of indoximod 1200 mg orally, twice daily in combination with docetaxel 75 mg/m2 every 3 weeks or paclitaxel 80 mg/m2 weekly in patients with metastatic ER/PR positive or negative, HER2 negative breast cancer. The trial, which reached its goal of 154 patients enrolled across multiple sites in the United States and Europe, is designed to evaluate the combination of indoximod and chemotherapy as first-line therapy for patients with metastatic breast cancer. The study's primary endpoint is progression-free survival, with secondary endpoints of overall survival, response rate per RECIST 1.1 criteria, safety, and immune response correlative assays.

Preliminary evaluable safety data from 128 patients, when considered in a blinded fashion pooling control and treatments arms of the study, suggests that the regimen is generally well tolerated. The addition of indoximod to standard of care chemotherapy for metastatic breast cancer did not increase expected adverse events known to be associated with the administered chemotherapies. Additionally, no unexpected safety signals were reported with the combination of indoximod with docetaxel or paclitaxel, suggesting that there is no additional or unique toxicity with the addition of indoximod to chemotherapy.

Objective responses were achieved in an earlier Phase 1 trial combining indoximod and docetaxel in patients with metastatic solid tumors, including breast tumors.

"I believe this is an exciting chemoimmunotherapy combination regimen for patients with metastatic breast cancer," said Shou-Ching Tang, M.D., Ph.D., Professor of Medicine, Leader, Breast Cancer Multidisciplinary Team at Augusta University. "These data suggest that indoximod may become a valuable addition to standard breast cancer treatment regimens due to the potential for enhancing a patient's immune system to fight cancer without additive toxicity. I eagerly await the full results of this trial evaluating a promising immune check point inhibitor in combination with chemotherapy."

The data, presented during the poster session "Treatment: Immunotherapy," correspond to the abstract (P2-11-09) entitled, "A phase 2 randomized trial of the IDO pathway inhibitor indoximod in combination with taxane based chemotherapy for metastatic breast cancer: preliminary data."

Indoximod is an orally available small molecule that has shown the potential to interfere with multiple targets within the indoleamine 2,3-dioxygenase (IDO) pathway. It is designed to be used in combination with other therapeutic agents to maximize the body's immune response against a range of tumor types. Indoximod is currently in multiple Phase 2 clinical trials for the treatment of patients with breast, prostate, pancreatic, melanoma and brain cancers and in Phase 1 clinical trials for the treatment of pediatric patients with primary malignant brain tumors.
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Source: press release, 12/10/15. http://investors.linkp.com/releasedetail.cfm?ReleaseID=946500

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April 2, 2013
NewLink Genetics Initiates Phase 2 Trial of IDO Pathway Inhibitor, Indoximod, for the Treatment of Metastatic Breast Cancer
Clinical Trial Designed to Evaluate Novel IDO Pathway Inhibitor in Combination with Docetaxel

AMES, Iowa, April 2, 2013 /PRNewswire/ -- NewLink Genetics Corporation (NASDAQ: NLNK), a biopharmaceutical company focused on discovering, developing and commercializing cancer therapeutics, today announced the initiation of a double-blind, randomized, placebo-controlled Phase 2 clinical study of its first IDO (indoleamine-(2,3)-dioxygenase) pathway inhibitor, indoximod, in patients with metastatic breast cancer. The Phase 2 clinical study will evaluate indoximod as a new approach to treating cancer by administering this novel IDO pathway inhibitor, designed to counteract a key mechanism by which tumors evade immune-mediated destruction, in combination with a conventional cytotoxin, docetaxel. This Phase 2 clinical study follows the successful Phase 1b dose-escalation study of indoximod in patients with advanced solid tumors in which a favorable safety profile and promising early signs of activity were observed. Indoximod is the most advanced product candidate to enter clinical trials based on NewLink's proprietary IDO pathway inhibitor platform for small-molecule, orally bioavailable cancer immunotherapies.

"There is significant unmet need for new approaches that may offer more effective treatment options for patients with metastatic breast cancer, a leading cause of death in women in the United States," said Hatem Soliman, MD, a medical oncologist specializing in breast cancer in The Center for Women's Oncology at Moffitt Cancer Center and the principal investigator for this study. "Indoximod has demonstrated promising safety, pharmacokinetic and biologic activity in earlier clinical studies and we look forward to increasing our understanding of its potential in metastatic breast cancer with this robust Phase 2 study designed to evaluate the activity of indoximod in combination with a conventional chemotherapy across a number of clinically relevant endpoints."

"Indoximod, an IDO pathway inhibitor is an immune check point inhibitor akin to the recently developed antibodies targeting CTLA-4 and PD-1. IDO can be expressed within both tumor cells and/or antigen presenting cells to create local immune suppression to impair immunological detection and destructions of tumors," commented Dr. Charles Link, Chairman and Chief Executive Officer of NewLink. "We are excited about the promising approach of using novel therapies, like indoximod, to harness key mechanisms of the immune system to enhance the body's cancer-fighting abilities and enhance the effect of other therapies. NewLink intends to pursue this strategy as we advance other clinical candidates from our IDO pathway inhibitor platform as well as our novel candidates from our HyperAcute immunotherapy platform."

This randomized, double-blind, placebo-controlled Phase 2 clinical study is designed to evaluate the safety and efficacy of indoximod in combination with docetaxel as compared to docetaxel alone in up to 120 patients with metastatic breast cancer. Study endpoints include progression-free survival, objective response rate, median overall survival and evaluation of pharmacodynamic tumor markers, in addition to safety. For more information about the study please refer to www.clinicaltrials.gov.
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Source: press release, 4/02/13. http://investors.linkp.com/releasedetail.cfm?ReleaseID=753656

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Study-NLG2101 - A Phase II Double-Blinded, Randomized, Placebo-Controlled Study of Docetaxel in Combination With 1-methyl-D-tryptophan (Indoximod) in Metastatic Breast Cancer
Enrollment: 169
Study Start Date: February 2013
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
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Source: clinical trials.gov. http://clinicaltrials.gov/ct2/show/NCT01792050?term=Indoximod&rank=1

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Compound/DeviceSpecialtyIndicationCompound ClassTarget
Indoximod Breast cancerOncologyBreast Cancer (metastatic)Anti-toleragenicIndoleamine-pyrrole 2,3-dioxygenase (IDO) pathway inhibitor

Mechanism of action: Indoximod (1-methyl-d-tryptophan) is a small molecule, methylated tryptophan, anti-immunosuppressive-toleragenic, Indoleamine-pyrrole 2,3-dioxygenase (IDO) pathway inhibitor. It is intended to counteract a key mechanism by which tumors evade immune-mediated destruction. IDO is an enzyme that regulates immune response by suppressing T-cell function and enabling local tumor immune escape. 1-methyl-d-tryptophan inhibits the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades the essential amino acid tryptophan, and may increase or maintain tryptophan levels important to T cell function. Tryptophan depletion is associated with immunosuppression involving T cell arrest and anergy. Recent studies have demonstrated that IDO is overexpressed in many cancers, within both tumor cells as a direct defense against T-cell attack, and also within antigen presenting cells in tumor draining lymph nodes whereby IDO promotes peripheral tolerance to tumor associated antigens (TAAs). When hijacked by developing cancers in this manner, IDO may facilitate the survival, growth, invasion, and metastasis of malignant cells expressing TAAs that might otherwise be recognized and attacked by the immune system as foreign.

Phase of Development: II

Event Type: Data: Phase II trial results

Dates: 2016-12-01 - 2017-03-31

Results: Pending