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

This is a Phase 1, open label, multi-center, nonrandomized, first in human, dose escalation trial of TRE-515 designed to evaluate safety and tolerability and determine the MTD and RP2D of orally administered TRE-515 as monotherapy in subjects with advanced solid tumors.

Safety assessments will include adverse events (AEs), dose limiting toxicities (DLTs), clinical laboratory values, vital signs, body weight, electrocardiograms (ECGs), and Eastern Cooperative Oncology Group (ECOG) performance status .

Dose-limiting toxicities will be assessed over the first 21 days on study. The PK and preliminary tumor response analyses will be conducted throughout the study.

Preliminary tumor responses will be assessed by the Principal Investigator (PI) based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1) using an appropriate modality (computer tomography \[CT\]/magnetic resonance imaging \[MRI\]) every 8 weeks.

In the dose escalation phase, subjects will be enrolled in sequential cohorts to receive TRE-515 as a daily oral dose using continuous 21-day cycles at escalating dose levels, as outlined in.

Subjects will continue to receive TRE-515 in the absence of progressive disease as defined by RECIST v1.1 or unacceptable toxicity. Following determination of an RP2D, an additional 6 subjects will receive TRE-515 at the RP2D to gain additional experience with the safety profile and additional evidence of activity.

In the dose escalation phase, a minimum of 3 subjects will be treated in each dose cohort using a conventional 3+3 dose escalation study design, starting at Cohort 1 . Cohort (-1) represents a contingency de-escalation dose level in the event that tolerance issues are encountered in Cohort 1. In each cohort, 3 subjects will be initially treated, and each subject will TRE515-T-02, be followed for the full DLT assessment period . In the absence of a DLT in the 3 subjects within a cohort, dose advancement will proceed through the successive cohorts. All subjects in each cohort must have completed the DLT observation period before the next dose cohort may open. Depending upon the tolerance at a particular dose level, intermediate dose levels may be studied to more closely characterize DLTs and more accurately identify the MTD as recommended by the Safety Review Committee (SRC). Individual subjects may continue receiving additional TRE-515 treatment until disease progression, unacceptable toxicity, or other reason for treatment discontinuation.