A Phase 1 Study of Bisaminoquinoline Derivative (TR-002) for Injection for Advanced Treatment-Refractory Solid Tumors
Summary
This phase I trial tests the safety, side effects and best dose of TR-002 for the treatment of solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced), that cannot be removed by surgery (unresectable), that has spread from where it first started (primary site) to other places in the body (metastatic) and unresectable or metastatic pancreatic adenocarcinoma that does not respond to treatment (refractory). Chemotherapy drugs, such as TR-002, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. TR-002 may be safe and tolerable in treating patients with advanced, unresectable or metastatic solid tumors and unresectable or metastatic, refractory pancreatic adenocarcinoma.
Detailed description
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD), which will also be the recommended phase 2 dose (RP2D) of Nadofaragene Firadenovec (TR-002) for the treatment of advanced treatment-refractory solid tumors. II. To evaluate the toxicities of TR-002 administered intravenous weekly. SECONDARY OBJECTIVES: I. To obtain preliminary assessment of anti-tumor activity of TR-002 administered intravenous weekly at the RP2D. II. To evaluate the pharmacokinetics of TR-002 administered intravenous weekly. EXPLORATORY OBJECTIVE: I. To assess the effects of TR-002 on pharmacodynamic biomarkers relating to the mechanism of action. OUTLINE: This is a dose-escalation study of TR-002 followed by a dose-expansion study. Patients receive TR-002 intravenously (IV), over 1 hour, on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography or multigated acquisition (MUGA) scan during screening and undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), tumor biopsy and blood sample collection throughout the study. After completion of study treatment, patients are followed up at 30 days and every 60 days for 1 year.
Arms & interventions
- DrugTR-002
Weekly intravenous infusion
Outcome measures
Primary
Incidence of dose limiting toxicity (DLTs)
The proportion of DLTs at each dose level will be reported with exact binomial 95% confidence intervals.
Time frame: From first dose of TR-002 to day 28
Number of participants experiencing treatment-related adverse events
Classified by severity, and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Time frame: From first dose of TR-002 to 90 days following the last dose
Secondary
Objective response rate (ORR)
Time frame: From the first dose of TR-002 up to 1 year post last dose
Progression free survival
Time frame: From the date of enrollment until the first occurrence of disease progression, or death from any cause, whichever occurs earlier, up to 1 year post last dose
Overall survival
Time frame: From the date of enrollment until death from any cause, up to 1 year post last dose
Steady state through concentrations in serum
Time frame: Within 15 minutes prior to Cycle 1 Day 1 infusion, end of Cycle 1 Day 15 infusion, and 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 24 hours post-Cycle 1 Day 15 infusion
Peak Plasma Concentration (Cmax)
Time frame: Within 15 minutes prior to Cycle 1 Day 1 infusion, end of Cycle 1 Day 15 infusion, and 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 24 hours post-Cycle 1 Day 15 infusion
Area under the serum concentration
Time frame: Within 15 minutes prior to Cycle 1 Day 1 infusion, end of Cycle 1 Day 15 infusion, and 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 24 hours post-Cycle 1 Day 15 infusion
Half-life
Time frame: Within 15 minutes prior to Cycle 1 Day 1 infusion, end of Cycle 1 Day 15 infusion, and 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 24 hours post-Cycle 1 Day 15 infusion
Apparent clearance/bioavailability
Time frame: Within 15 minutes prior to Cycle 1 Day 1 infusion, end of Cycle 1 Day 15 infusion, and 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 24 hours post-Cycle 1 Day 15 infusion
Apparent volume of distribution
Time frame: Within 15 minutes prior to Cycle 1 Day 1 infusion, end of Cycle 1 Day 15 infusion, and 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 24 hours post-Cycle 1 Day 15 infusion
Eligibility criteria
Study locations (1)
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
References
- Mahri S, Tang M, Zong Q, Kim EJ, Lin TY, Li Y. Towards the clinical translation of a novel autophagy inhibitor: Bisaminoquinoline derivative nanoparticles. Biomaterials. 2026 Jun 2;335:124361. doi: 10.1016/j.biomaterials.2026.124361. Online ahead of print.(PubMed)