Open-Label, Dose-Escalation With Expansion to Assess the Safety, Tolerability, and PK of TRE-515 in Subjects With Solid Tumors

Part of paid clinical trials in Santa Monica, California.

Sponsor
Trethera
Study ID
NCT05055609
Phase
PHASE1
Status
Recruiting
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Conditions

  • Oncology
  • Solid Tumor, Adult

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • TRE-515 — DRUG
    TRE-515 will be administered orally once daily at least 1 hour prior or 2 hours after eating at approximately the same time each day. Dosing will be continuous with no breaks between cycles. Subjects will continue to receive successive cycles of TRE-515 treatment as long as they do not demonstrate progressive disease, experience an unacceptable toxicity, and both the Sponsor and PI consider additional treatment with TRE-515 to be within the best interest of the subject.

Study Details

TRE-515 is a first-in-class small molecule inhibitor of deoxycytidine kinase (dCK) that is being developed for oral administration in patients with solid tumors. In cancer cells, rapid and upregulated DNA replication creates high replication stress, as such, cancer cells are more susceptible than normal cells to perturbations in nucleotide metabolism by DNA-targeting treatments such as TRE-515. The Primary objective is to determine the safety and maximum tolerability of TRE-515 when administered orally once daily as a single agent. The secondary objectives are to establish a recommended phase 2 dose (RP2D), to characterize pharmacokinetics (PK) and pharmacodynamics (PD) of TRE-515, preliminary evaluation of antitumor activity, and to determine the effect of an acid reducing agent (ARA) on TRE-515 exposure. The exploratory objectives are to evaluate the relationship between TRE-515 exposure and plasma deoxynucleoside concentrations, evaluate the relationship between TRE-515 exposure and reductions in intracellular dCK on-target knockdown as measured by a \[18F\]-clofarabine (CFA) positron emission tomography (PET) probe, to evaluate the relationship between TRE-515 treatment and dCK and CDA gene expression in archived tumor tissue when available, to evaluate the relationship between tumor CDA and plasma deoxynucleoside (dC and dU) concentrations, and to explore the effect of TRE-515 treatment on gene expression in white blood cell populations.

Key Dates

Start date
Sep 23, 2021
Status verified
May 2025
Primary completion
Dec 31, 2026
Completion
Jun 1, 2027

Study Design

Enrollment
94 participants (estimated)
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Open Label
    In the dose escalation portion, will enroll up to 46 subjects in five or more cohorts. The dose expansion portion will enroll up to 48 subjects. The actual number of subjects enrolled will depend on the safety data and additional evidence of antitumor activity.

Primary Outcome Measure

Safety and Tolerability of TRE-515 as assessed by the Number of Participants with Adverse Events (AEs) as assessed by NCI-CTCAE v5.0Safety and tolerability of oral TRE-515 [ Time Frame: up to 60 months ]

Central Contacts

Locations (2)

FacilityCityStateZIPSite coordinators
UCLASanta MonicaCalifornia90404
Lisa Yonemoto
310-633-8400
Zev Wainberg, MD (PRINCIPAL_INVESTIGATOR)
Carolina BioOncology InstituteHuntersvilleNorth Carolina28078
Sydney Noldin
704-947-6599
John Powderly, MD (PRINCIPAL_INVESTIGATOR)

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