Phase I, Multicenter, Cohort Dose Escalation Trial to Determine the Safety, Tolerance, and Maximum Tolerated Dose of DCR-MYC, a Lipid Nanoparticle (LNP)-Formulated Small Inhibitory RNA (siRNA) Oligonucleotide Targeting MYC, in Patients With Refractory Locally Advanced or Metastatic Solid Tumor Malignancies, Multiple Myeloma, or Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- DCR-MYC
- Conditions
- Solid Tumors
- Sponsor
- Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
- Enrollment
- 50
- Locations
- 6
- Primary Endpoint
- Number of patients with adverse events as a measure of safety and tolerability
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study is to assess the safety and tolerability of the investigational anticancer drug DCR-MYC. DCR-MYC is a novel synthetic double-stranded RNA in a stable lipid particle suspension that targets the oncogene MYC. MYC oncogene activation is important to the growth of many hematologic and solid tumor malignancies. In this study the Sponsor proposes to study DCR-MYC and its ability to inhibit MYC and thereby inhibit cancer cell growth.
Detailed Description
In this first-in human study, DCR-MYC will be administered by 2 hour intravenous (IV) infusion, once weekly for 2 weeks followed by a rest week (3 weeks = 1 cycle), to patients with either solid tumor malignancies, multiple myeloma, or non-Hodgkins lymphoma that have not responded to previous treatment. The highest safe dose of DCR-MYC that can be administered will be identified. In addition, the pharmacokinetic (PK) profile, potential pharmacodynamic (PD) effects, as well as the antitumor activity of DCR-MYC will be evaluated. There will be 2 expansion cohorts at the maximum tolerated dose (MTD) (or highest safe dose identified for further study which may be lower): * Biopsy Cohort: 6 patients, tumor biopsies to be performed pre-dosing and Cycle 2/Day 11; same assessments as dose escalation cohorts * PNET Cohort: Up to 20 patients with pancreatic neuroendocrine tumors; same assessments as dose escalation cohorts, however fewer PD (cytokine) assessments and no PK assessments
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female patients, \> 18 years of age at the time of obtaining informed consent.
- •Patients with a documented solid tumor malignancy that is locally advanced or metastatic; patients with documented multiple myeloma or non-Hodgkin's lymphoma.
- •Patients with a malignancy that is either refractory to standard therapy or for which no standard therapy is available.
- •Patients with a malignancy that is currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.
- •Dose escalation portion of study: Patients with measurable or non-measurable disease according to standard response criteria .
- •MTD Biopsy Cohort ONLY: Patients with measurable disease with primary or metastatic tumor site(s) considered safely accessible for biopsy; patients must consent to undergo 2 tumor biopsies.
- •MTD PNET Cohort ONLY: Patients with advanced (unresectable or metastatic), histologically-confirmed low or intermediate grade PNET according to the World Health Organization (WHO) 2010 classification. Patients with neuroendocrine tumors (e.g., gastrinoma, VIPoma) in whom a pancreatic or peripancreatic primary is strongly suspected are also eligible. Patients must also have:
- •A Ki-67 proliferation index \< 20%
- •Demonstrated radiological evidence of disease progression during or following the last treatment regimen (based on CT, MRI, or Octreoscan®)
- •Measurable disease according to RECIST v1.1 (determined by CT or MRI). Any lesions which have been subjected to percutaneous therapies or radiotherapy should not be considered measureable, unless the lesion has clearly progressed (per RECIST v1.1) since the procedure.
Exclusion Criteria
- Not provided
Arms & Interventions
DCR-MYC
Patient groups (cohorts) will receive a single dose level of DCR-MYC; the dose level of DCR-MYC will be increased in subsequent cohorts
Intervention: DCR-MYC
Outcomes
Primary Outcomes
Number of patients with adverse events as a measure of safety and tolerability
Time Frame: Cycle 1 (3 weeks), longer if DRC-MYC is continued; with 30 days follow-up after last dose
Part A: 1 patient cohorts with 100% dose increase between cohorts until \>/= Grade 2 study drug-related toxicity during Cycle 1, then expand to 3 patients and move to Part B. Part B: 3 patient cohorts with 50% dose increase between cohorts until study drug-related DLT during Cycle 1, then expand to 6 patients and move to Part C. Part C: 3 to 6 patient cohorts with 25% dose increase between cohorts until \> 1 study drug-related DLT, then stop escalation and expand previous MTD cohort to 18 patients.
Secondary Outcomes
- DCR-MYC levels in blood(Cycle 1; Week 1 and Week 2)
- DCR-MYC biological activities(Cycle 1 and Cycle 2)
- Preliminary antitumor activity(After Cycle 2 (6 weeks), then at 6 week intervals if DCR-MYC is continued)