TR-002 (Nadofaragene Firadenovec) given by IV for adults with advanced unresectable or metastatic solid tumors and refractory metastatic pancreatic adenocarcinoma
A Phase 1 Study of Bisaminoquinoline Derivative (TR-002) for Injection for Advanced Treatment-Refractory Solid Tumors
This Phase 1 trial tests whether weekly intravenous TR-002 is safe and what dose is best for adults with advanced unresectable or metastatic solid tumors or refractory metastatic pancreatic cancer.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 52 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of California, Davis Academic / other |
| Drugs / interventions | Chemotherapy |
| Locations | 1 site (Sacramento, California) |
| Trial ID | NCT07189195 on ClinicalTrials.gov |
What this trial studies
This is a Phase 1, dose-escalation followed by dose-expansion study of TR-002 given intravenously on days 1, 8, 15 and 22 of a 28-day cycle to determine the maximum tolerated dose and recommended Phase 2 dose. Safety and side effects are the primary focus, with secondary assessments of early anti-tumor activity, pharmacokinetics, and pharmacodynamic biomarkers. Participants undergo routine imaging, blood tests, and tumor biopsy when feasible, and cardiac function is evaluated before enrollment. Participants are followed after treatment for safety and disease status for up to one year.
Who should consider this trial
Good fit: Adults (18+) with pathology-confirmed unresectable or metastatic solid tumors no longer responding to or intolerant of standard systemic therapies — with the expansion cohort limited to patients with refractory metastatic pancreatic adenocarcinoma and measurable disease per RECIST 1.1 and adequate cardiac function.
Not a fit: Patients who still have effective standard treatment options, who have resectable early-stage disease, or who have significant cardiac dysfunction are unlikely to benefit from this trial.
Why it matters
Potential benefit: If successful, TR-002 could become a new treatment option for patients with heavily pretreated advanced solid tumors and refractory metastatic pancreatic adenocarcinoma.
How similar studies have performed: Viral-vector and gene-delivery approaches have shown activity in some cancer settings and nadofaragene firadenovec is approved for intravesical bladder cancer, but systemic IV administration of this agent for solid tumors is a novel and early approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Aged 18 or over at the time of consent * Pathology or histology-confirmed metastatic or unresectable solid tumor for which standard systemic treatments are no longer effective or not tolerated * For the expansion cohort, participants must have pathology or histology-confirmed metastatic or unresectable pancreatic adenocarcinoma that is refractory and/or intolerant to all standard-of-care systemic treatments (including gemcitabine, nab-paclitaxel, fluoropyrimidine, oxaliplatin, and irinotecan) * Participants in dose escalation may have measurable and/or non-measurable disease. Imaging for disease assessment of measurable and non-measurable disease must be completed within 28 days prior to registration. Participants in dose expansion must have measurable disease per Response Evaluation Criteira in Solid Tumors (RECIST) 1.1 * Adequate cardiac function, assessed by multiple-gated acquisition (MUGA) scan or echocardiography (left ventricular ejection fraction of \> 50%) * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Absolute neutrophil count ≥ 1,000/mcL * Platelets ≥ 75,000/mcL * Hemoglobin ≥ 8g/dL * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (\< 3 x ULN in patients with known Gilberts) * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN (\< 5 x ULN in patients with known liver metastases) * Creatinine ≤ 1.5 x institutional ULN OR glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 * For people of reproductive potential: use of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method through 3 months following the last dose of study treatment * Provision of signed and dated informed consent form * Stated willingness to comply with all study procedures and availability for the duration of the study Exclusion Criteria: * Lactating or pregnant patients or patients of reproductive potential not willing to use effective methods of contraception * Clinically significant toxicities from most recent therapy or intervention prior to study enrollment that have not resolved to baseline or grade 1 (exceptions include alopecia and grade 2 sensory neuropathy) * Participant with a history of the following significant cardiovascular disease will be excluded: * Participant has a history of myocardial infarction or unstable angina within 6 months prior to day 1. * Participant has New York Heart Association (NYHA) Class II or greater congetive heart failure (CHF). * History of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to study treatment. * Participant has cardiac arrhythmia, complete left bundle branch block, obligate use of a cardiac pacemaker, long QT syndrome or right bundle branch block with left anterior hemiblock (bifascicular block). * History of congenital long QT syndrome or prolonged corrected QT interval (QTc) \> 470 msec for females and males using Fridericia's formula (unless a pacemaker is in place or additional clinically non-significant condition such as bundle-branch block necessitating use of an alternate formula per cardiologist calculation) or uncorrectable abnormalities in serum electrolytes (i.e., sodium, potassium, calcium, magnesium, phosphorus). An average of triplicate readings for assessing QTc interval may be used * Active bacterial, fungal, and viral infection, as documented by positive culture, radiological imaging techniques, septic fever, or septic shock symptoms * Known hypersensitivity to 4-aminoquinolone compounds * Retinal or visual field changes of any etiology * History of psoriasis * History of porphyria * Known glucose-6-phosphate dehydrogenase (G6PD) deficiency * History of seizure disorder * Any other condition that could compromise the subject's safety or put the study outcomes at undue risk
Where this trial is running
Sacramento, California
- University of California Davis Comprehensive Cancer Center — Sacramento, California, United States (Recruiting)
Study contacts
- Principal investigator: Edward J Kim, MD — University of California, Davis
- Study coordinator: OCR Referral Team
- Email: OCRReferral@health.ucdavis.edu
- Phone: 916-382-6970
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.