TRE-515 for Cancer

Recruiting at 1 trial location

Overseen By Allen Clark

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Trethera

Must not be taking: Anticancer, Adjuvant, Investigational, others

Disqualifiers: Organ transplant, Uncontrolled infection, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

94 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that you cannot participate if you require any prohibited medications. It's best to discuss your current medications with the trial team to see if they are allowed.

Are You a Good Fit for This Trial?

Adults with confirmed solid tumors who have measurable disease and can undergo PET scans. They should be in a stable health condition (ECOG 0-2), have recovered from previous treatments, and show adequate organ function in lab tests. Participants must not have significant heart issues, other active cancers (with some exceptions), or severe medical/psychiatric conditions that could affect study compliance.

Inclusion Criteria

Measurable disease, per RECIST v1.1

I have recovered from side effects of previous cancer treatments.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

QTcB prolongation of >470 msec (confirmed on triplicate ECGs performed at least 5 minutes apart)

I do not have any ongoing serious infections requiring treatment.

Known hypersensitivity to the drug or excipients contained within the drug formulation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Subjects receive TRE-515 in sequential cohorts with escalating doses to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D).

21-day cycles

Visits on Day 1, 8, and 15 of each cycle

Dose Expansion

Additional subjects receive TRE-515 at the RP2D to further evaluate safety and antitumor activity.

Up to 18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TRE-515

Trial Overview The trial is testing the safety and tolerability of TRE-515, an oral drug designed to disrupt cancer cell DNA replication by inhibiting dCK. The goal is to find the highest dose patients can take without serious side effects (maximum tolerable dose) and recommend a phase 2 dose while also studying how the body processes the drug.

How Is the Trial Designed?

Group I: Open Label Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Trethera

Lead Sponsor

Trials

1

Recruited

90+