Multi-center Phase I study of anti-VISTA opens for patient enrollment

Dartmouth and Dartmouth-Hitchcock Norris Cotton Cancer Center (NCCC) will serve as one of the lead institutions for a new multi-center clinical trial of anti-VISTA, now open and recruiting for patient enrollment. The trial is a Phase I study of CI-8993, an anti-VISTA (V-domain Ig Suppressor of T-cell Activation) antibody, in adult patients with advanced solid tumors.

VISTA is a checkpoint regulator whose function is to prevent activation of the immune system to self-antigens such as developing cancer cells. Its presence is strong in several tumor types including pancreatic, lung, and prostate cancer. VISTA was discovered as a potential therapeutic target by NCCC's Randolph Noelle, PhD, Member of the Immunology and Cancer Immunotherapy Research Program at NCCC and Kosasa Distinguished Professor of Microbiology and Immunology at the Geisel School of Medicine at Dartmouth.

In preclinical experiments, the anti-VISTA antibody, CI-8993, developed by ImmuNext, Inc. (co-founded by Noelle) can target VISTA, reverse tumor immune suppression, and potentially allow for generation of anti-tumor responses.

VISTA is a protein with high levels of expression in certain immune cells, such as the ones that are present in or around tumors with suppressed T-cell activation. The discovery of VISTA and subsequent work by Dartmouth researchers, including Dr. Noelle, provide a compelling foundation for further evaluation, and we are delighted to have the opportunity to participate in this Phase I study to further evaluate CI-8993."

Jason Faris, MD, Principal Investigator of the trial for NCCC, and Director of the Early-Phase Trials Program at NCCC

Study coordinators plan to enroll approximately 50 patients across several participating cancer centers. NCCC is the first to open the study, which will have three to six patient slots per dose level. Cohorts are open to patients with metastatic or unresectable solid tumors who are considered relapsed and/or refractory to prior therapy and meet several other criteria, as specified on clinicaltrials.gov.

Each patient will be administered a low dose of CI-8993, called a step dose and monitored carefully. If there are no safety concerns following the step dose, the patient will receive the first full dose of the drug a week later. If the dose level initially tested is considered to be safe, then the next group of patients to be enrolled onto the clinical trial would be enrolled to a higher dose level.

The study is sponsored by Curis, Inc, a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer. Earlier this year, Curis entered into an agreement with ImmuNext, Inc. to develop and commercialize anti-VISTA antibodies, including CI-8993, for the treatment of cancer.

Phase I studies are designed to determine safety and tolerability of experimental therapeutics as well as to document any early potential signs of anti-cancer activity. Primary outcome measures of this trial include determining both the maximum tolerated dose of CI-8993 and determining the recommended Phase 2 dose. This Phase I study is expected to enroll patients over approximately two years.

"This trial represents a remarkable example of Dartmouth basic science discoveries being brought to the clinic for the benefit of our patients," says NCCC Director, Steven Leach, MD. "VISTA was discovered as potential therapeutic target by Dr. Noelle right here at NCCC, and therapeutic antibodies were developed by ImmuNext, a local biotech company housed within our medical center. We are honored to serve as one of the lead academic institutions for this multi-center trial that represents a wonderful example of bench-to-bedside science at NCCC."

Jason Faris, MD, is the Director of the Early-Phase Trials Program, member of the Cancer Biology and Therapeutics Research Program, and a practicing medical oncologist in the Gastrointestinal Oncology Program at Dartmouth's and Dartmouth-Hitchcock's Norris Cotton Cancer Center, focusing on pancreatic, colorectal and hepatobiliary cancers. He is also Assistant Professor of Medicine at the Geisel School of Medicine at Dartmouth.