On November 23, 2015 NewLink Genetics Corporation (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, reported a trial update from a Phase 1b/2 study of indoximod in combination with temozolomide presented on November 20 at the 20th Annual Scientific Meeting of the Society for Neuro-Oncology in San Antonio, Texas (Press release, NewLink Genetics, NOV 23, 2015, View Source [SID:1234508326]).
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Indoleamine 2,3-dioxygenase (IDO) is a key immuno-modulatory enzyme that allows tumors to thwart the host immune response and therefore is an important research target. IDO is expressed in a large proportion of solid tumors, including 50-90% of glioblastoma tumors. Indoximod is NewLink Genetics’ proprietary product candidate that has shown the potential to interfere with multiple targets within the IDO pathway and thereby to unleash the immune system to fight cancer.
The update presented is from a Phase 1b/2 study of indoximod in combination with temozolomide in patients with advanced glioblastoma who have previously demonstrated that their tumors are refractory to temozolomide. The completed Phase 1b portion of the study, which enrolled 12 patients, continues to show that the combination has an acceptable safety profile, confirming data previously presented. This Phase 1b portion of the study also demonstrated preliminary efficacy of the combination therapy. A six-month progression free survival (PFS) rate of 25% was observed, which compares favorably to the historical rate of 15% for refractory glioblastoma. In addition, the patient previously reported as having achieved a radiographically confirmed partial response (PR) remains on study treatment and has thus far demonstrated a durable response of greater than eight months, with an overall survival on trial of 20 months.
The Phase 2 portion of the study, which aims to determine the preliminary efficacy of the combination therapy, has enrolled 40 of a planned 132 patients as of the data cutoff. Nine of the 40 patients have been enrolled for more than six months and seven are evaluable as to outcome. One of these seven patients has demonstrated a radiographically confirmed PR after previously being refractory to treatment with temozolomide. The objective response occurred after having stable disease on treatment for six months. Of note, the onsets of the two partial responses, one in Phase 1b and one in Phase 2, were delayed, suggesting a possible immunotherapy-based mechanism of response.
"It is encouraging to see some promising early signs of activity of this combination of an immunotherapy with standard chemotherapy in recurrent GBM, which is a disease with huge unmet need," said Howard Colman, MD, PhD, Associate Professor of Neurosurgery and Director of Medical Neuro-Oncology at the Huntsman Cancer Institute at the University of Utah and an author of the study.
"I am particularly impressed with the potential early signals of an immune-mediated effect, as evidenced by the delayed onset and durability of the responses observed," said Olivier Rixe, MD, PhD, Professor of Medicine and Associate Director for Clinical Research at the University of New Mexico Comprehensive Cancer Center and an author of the study. "This is one of the first clinical trials testing an immune checkpoint inhibitor in glioblastoma. It shows that indoximod is the first such therapy to produce an objective response in glioblastoma."
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"We are pleased with the preliminary safety and efficacy data on the combination of indoximod and temozolomide in glioblastoma obtained so far in this study," said Nicholas Vahanian, M.D., President and Chief Medical Officer. "We look forward to learning more about indoximod in our clinical studies in glioblastoma and four other cancer types, as well as about our six other immuno-oncology products currently in clinical testing."