The first federally funded clinical trial of immunotherapy for rare cancers launched this week under the auspices of SWOG, the research consortium headquartered at the OHSU Knight Cancer Institute. Over 30 different types of rare cancers – defined as less than a 6 in 100,000 incidence per year – will be studied.
The DART trial is testing the combined use of ipilimumab, a monoclonal antibody targeting the T-cell antigen CTLA4, and nivolumab, a monoclonal targeting the PD-1 receptor. The combination proved to be strikingly effective against melanoma, fueling enthusiasm for testing it in a wide array of solid tumors.
“Investigators leading the DART trial want to determine if this combination, given in six-week cycles, can significantly shrink tumors, based on computerized tomography scans taken upon enrollment, then at regular intervals over the course of treatment,” SWOG leaders explained in a news release. The National Cancer Institute funded the trial and made collaborative agreements with Bristol-Myers Squibb for access to ipilimumab and nivolumab.
To be eligible for the DART trial, patients must first be registered with NCI-MATCH, an umbrella trial attempting to match patients with treatments that target a specific tumor mutation or signaling pathway. Patient with rare tumors can enroll in the DART trial if they have no treatment option in NCI-MATCH, or don’t respond to treatment in that trial.
DART – Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors
Primary objective: Evaluate the overall response rate, using RECIST criteria, in subsets of patients with advanced rare cancers treated with ipilimumab plus nivolumab combination immunotherapy.
Secondary objectives: 1. Evaluate toxicities in each cohort. 2. Estimate overall survival, progression-free survival, clinical benefit rate, immune-related overall response rate, and immune-related progression free survival. 3. Collect specimens for banking for use in future correlative biomarker research studies.
Methods: Patients receive nivolumab intravenously over 30 minutes on days 1, 15, and 29 and ipilimumab intravenously over 60 minutes on day 1. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 10 years from registration.
Inclusion Criteria: Patients must have histologically confirmed rare cancer and/or cancer of unknown primary, that did not have a match to a molecularly-guided therapy in the NCI-MATCH trial, or who progressed on molecularly-matched therapy and have no further molecularly-matched treatment recommendations per NCI-MATCH.
Expected enrollment: 300 patients.
More details are available at ClinicalTrials.gov
The DART principal investigator is Sandip Patel, M.D., an assistant professor of medicine at UC San Diego Moores Cancer Center. Senior study chairs are Razelle Kurzrock, M.D., senior deputy center director at the University of California San Diego Moores Cancer Center, and Francis J. Giles, M.D., deputy director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. The study team includes the Knight Cancer Institute’s Christopher Ryan, M.D., a professor in the Division of Hematology and Medical Oncology in the OHSU School of Medicine.