Dicerna Pharmaceuticals, Inc., a leader in the development of RNAi therapeutics, today presented preliminary safety and efficacy data from an ongoing Phase 1 study of DCR-MYC in patients with advanced solid tumors, multiple myeloma, or lymphoma at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting.
DCR-MYC is an investigational Dicer substrate short interfering RNA (DsiRNA) therapeutic targeting the MYC oncogene. The interim data provide evidence of clinical and metabolic response in patients across several dose levels. Of particular significance, evidence of clinical anti-tumor activity was observed in two patients with advanced, treatment refractory pancreatic neuroendocrine tumors (PNETs).
Anthony W. Tolcher, M.D., FRCP(C), director of clinical research at South Texas Accelerated Research Therapeutics (START) and a principal investigator in the study, presented the data during the ASCO Tumor Biology oral abstract session. The presentation is titled Safety and activity of DCR-MYC, a first-in-class Dicer substrate small interfering RNA (DsiRNA) targeting MYC, in a phase 1 study in patients with advanced solid tumors.
“We are very pleased that DCR-MYC has been well-tolerated thus far,” said Dr. Tolcher. “The evidence of anti-tumor activity seen in patients with advanced PNET is particularly exciting. It was remarkable to see a metabolic response in a patient with PNET following just one cycle of treatment, followed by a response to re-treatment after a break of almost a year during which the patient remained progression-free. The data in PNET patients merit further exploration of DCR-MYC in this difficult to treat tumor.”
The ongoing Phase 1 study, initiated in April 2014, is a multi-center, dose escalation trial designed to assess the safety and tolerability of DCR-MYC in patients with advanced solid tumors, multiple myeloma, or lymphoma who are refractory or unresponsive to standard therapies. The study is also designed to identify the compound’s maximum tolerated dose (MTD), the pharmacokinetic (PK) profile, potential pharmacodynamic (PD) effects using F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging, and anti-tumor activity based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
In the study, DCR-MYC is administered as a two-hour intravenous (IV) infusion once-weekly for two weeks, followed by a one week break (3 weeks = 1 cycle). All patients receive premedications with dexamethasone, diphenhydramine, and an H-2 blocker. The starting dose was 0.1 mg/kg, with current dosing at 0.68 mg/kg. Dose-escalation will continue until the MTD is established. Pre- and post-dosing tumor biopsies will be obtained in a cohort of patients enrolled at MTD.
As of May 12, 2015, 26 patients were treated with DCR-MYC, with 18 patients evaluable for response. Anti-tumor activity was seen in two out of three patients with advanced, treatment refractory PNET. Specifically, evidence of a complete metabolic response based on imaging with FDG-PET was seen in one patient, and a partial tumor response (34% reduction in tumor size) based on RECIST 1.1 criteria in another. Both patients were treated with multiple therapies for PNET prior to starting the study.
Based on these interim study findings, Dicerna announced in May 2015 an expansion of the ongoing DCR-MYC Phase 1 trial to include a cohort of patients with PNET. Once the MTD is established, the multi-center expansion cohort will enroll up to 20 patients with low- to intermediate-grade PNET who have demonstrated disease progression after treatment with standard therapies.
“The preliminary Phase 1 safety and efficacy results are encouraging and support further study of DCR-MYC for use as a new treatment option for patients with cancer,” said Pankaj Bhargava, M.D., Dicerna chief medical officer. “We are currently enrolling patients in the seventh cohort of the study. Once the maximum tolerated dose is established, we will open enrollment for a multi-center expansion cohort in patients with advanced PNET. In addition to the Phase 1 study, we continue to enroll patients in our Phase 1b/2 trial of DCR-MYC in patients with hepatocellular carcinoma (HCC). We are pleased with the progress of both of these studies.”