A Trial of HTI-1090 in Subjects With Advanced Solid Tumors

NCT03208959 | Completed Phase 1 FDA Drug

• 1 other identifier: HTI-1090-101
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Adverse events

  Incidence of AEs

  Cycle 1 (each cycle is 21 days)

• Laboratory results

  Incidence of laboratory abnormalities

  Cycle 1 (each cycle is 21 days)

• Vital signs

  Incidence of vital sign abnormalities

  Cycle 1 (each cycle is 21 days)

• Electrocardiogram

  Incidence of ECG abnormalities

  Cycle 1 (each cycle is 21 days)

Study Arms (5)

Dose level 1

EXPERIMENTAL

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

Drug: HTI-1090

Dose level 2

EXPERIMENTAL

100% Increment from dose level 1

Drug: HTI-1090

Dose level 3

EXPERIMENTAL

100% Increment from dose level 2

Drug: HTI-1090

Dose level 4

EXPERIMENTAL

100% Increment from dose level 3

Drug: HTI-1090

Dose level 5

EXPERIMENTAL

50% Increment from dose level 4

Drug: HTI-1090

Interventions

HTI-1090 DRUG

IDO/TDO inhibitor

Also known as: SHR9146

Dose level 1; Dose level 2; Dose level 3; Dose level 4; Dose level 5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

To be eligible to participate in this study, each subject must meet all of the following criteria: 1. Provision of signed fully informed consent prior to any study specific procedures 2. Male or female aged 18 years or older 3. Diagnosed (histologically or cytologically) with solid tumors and documented as advanced or metastatic disease for which there is no known effective anti-tumor treatment (refractory to or relapsed from standard therapies) 4. Subjects may have received one prior IDO, or TDO, or IDO/TDO dual inhibitor therapy; PD-1 or PD-L1 inhibitor; or other therapy that targets T cell co-stimulation or co-inhibition more than 4 weeks prior to the first dose of HTI-1090 (Cycle 1, Day 1) 5. An ECOG Performance Status (PS) of 0 or 1 6. Have a life expectancy ≥ 12 weeks from proposed first dose date 7. Patients must have had no recent major surgery, radiotherapy or chemotherapy over the past 28 days and be fully recover from toxicity before dosing 8. Adequate laboratory parameters during the Screening Period as evidenced by: * Absolute neutrophil count ≥ 1.5×109/L (1,500/mm3) * Platelets ≥ 100×109/L (100,000/mm3) * Hemoglobin (Hgb) ≥ 9.0 g/dL (90 g/L) * Subjects may be transfused with red blood cells to improve Hgb levels. * Total bilirubin ≤ 1.5×ULN (≤ 2×ULN for subjects with liver metastases) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; for subjects with liver metastases, ALT and AST ≤ 5×ULN * Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min (measured or calculated by Cockcroft-Gault method) * Clinically relevant and treatment resistant abnormalities in potassium, sodium, calcium (corrected for plasma albumin) or magnesium 9. Evidence of post-menopausal status, permanent or surgically sterile, or negative serum pregnancy test for female patients of child-bearing potential. Women will be considered post-menopausal if they are over 50 years old and have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments. Permanent sterilization includes hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy but excludes bilateral tubal occlusion. Tubal occlusion is considered a highly effective method of birth control but does not absolutely exclude the possibility of pregnancy. (The term occlusion refers to both occluding and ligating techniques that do not physically remove the oviducts). Women who have undergone tubal occlusion should be managed as if they are of child-bearing potential (e.g., undergo pregnancy testing as required by the study). Females of reproductive potential are required to use reliable contraception 10. Patients must have ability to take and retain oral medication and have no malabsorption problems 11. Willing and able to return to treatment center for follow up, as outlined as protocol

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Atridia Pty Ltd.: lead

Study Sites (1)

Icon Cancer Care Centre

South Brisbane, New South Wales, 4101, Australia

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2017
• First Posted: July 6, 2017
• Study Start: August 30, 2017
• Primary Completion: November 1, 2018
• Study Completion: January 23, 2019
• Last Updated: July 20, 2022

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)