A Phase I, Open-Label, Multicenter, Non-Randomized, Dose-Escalation Study to Evaluate the Safety and Tolerability of HTI-1090 in Patients With Advanced Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Atridia Pty Ltd.
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Vital signs
Study Overview
Brief Summary
IDO1 is expressed in a wide variety of human tumors (eg. bladder, breast, colon, DLBCL, HNSCC, lung, ovarian, uterine, renal...), and contributes to tumoral resistance. HTI-1090 (also referred as SHR9146 in nonclinical study reports) is an orally bioavailable, highly potent, novel small-molecule IDO1/TDO dual inhibitor, with favorable preclinical oral bioavailability and safety profiles.
Detailed Description
This is an open-label, dose escalation, phase I, study of HTI-1090 (also known as SHR9146), a small molecule that inhibits both indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) - two enzymes that catalyze the oxidation of L-tryptophan (Trp) into kynurenine (Kyn), thereby interrupting the immune escape and the attainment of immunologic tolerance. Dose escalation will use a modified "3+3" design and continue until a MTD or RP2D is identified. This study will also characterize the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HTI-1090 in subjects with advanced solid tumors.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Dose level 1
HTI-1090 tablets will be orally administered on an empty stomach,twice daily, BID i.e., dosing will be 12 hours apart and at approximately the same times each day
Intervention: HTI-1090 (Drug)
Dose level 2
100% Increment from dose level 1
Intervention: HTI-1090 (Drug)
Dose level 3
100% Increment from dose level 2
Intervention: HTI-1090 (Drug)
Dose level 4
100% Increment from dose level 3
Intervention: HTI-1090 (Drug)
Dose level 5
50% Increment from dose level 4
Intervention: HTI-1090 (Drug)
Outcomes
Primary Outcomes
Vital signs
Time Frame: Cycle 1 (each cycle is 21 days)
Incidence of vital sign abnormalities
Electrocardiogram
Time Frame: Cycle 1 (each cycle is 21 days)
Incidence of ECG abnormalities
Adverse events
Time Frame: Cycle 1 (each cycle is 21 days)
Incidence of AEs
Laboratory results
Time Frame: Cycle 1 (each cycle is 21 days)
Incidence of laboratory abnormalities
Secondary Outcomes
No secondary outcomes reported