- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03208959
A Trial of HTI-1090 in Subjects With Advanced Solid Tumors
July 18, 2022 updated by: Atridia Pty Ltd.
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
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.
Study Overview
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 Type
Interventional
Enrollment (Actual)
18
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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New South Wales
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South Brisbane, New South Wales, Australia, 4101
- Icon Cancer Care Centre
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
To be eligible to participate in this study, each subject must meet all of the following criteria:
- Provision of signed fully informed consent prior to any study specific procedures
- Male or female aged 18 years or older
- 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)
- 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)
- An ECOG Performance Status (PS) of 0 or 1
- Have a life expectancy ≥ 12 weeks from proposed first dose date
- Patients must have had no recent major surgery, radiotherapy or chemotherapy over the past 28 days and be fully recover from toxicity before dosing
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
- 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
- Patients must have ability to take and retain oral medication and have no malabsorption problems
- Willing and able to return to treatment center for follow up, as outlined as protocol
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: 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
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IDO/TDO inhibitor
Other Names:
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EXPERIMENTAL: Dose level 2
100% Increment from dose level 1
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IDO/TDO inhibitor
Other Names:
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EXPERIMENTAL: Dose level 3
100% Increment from dose level 2
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IDO/TDO inhibitor
Other Names:
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EXPERIMENTAL: Dose level 4
100% Increment from dose level 3
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IDO/TDO inhibitor
Other Names:
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EXPERIMENTAL: Dose level 5
50% Increment from dose level 4
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IDO/TDO inhibitor
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse events
Time Frame: Cycle 1 (each cycle is 21 days)
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Incidence of AEs
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Cycle 1 (each cycle is 21 days)
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Laboratory results
Time Frame: Cycle 1 (each cycle is 21 days)
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Incidence of laboratory abnormalities
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Cycle 1 (each cycle is 21 days)
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Vital signs
Time Frame: Cycle 1 (each cycle is 21 days)
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Incidence of vital sign abnormalities
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Cycle 1 (each cycle is 21 days)
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Electrocardiogram
Time Frame: Cycle 1 (each cycle is 21 days)
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Incidence of ECG abnormalities
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Cycle 1 (each cycle is 21 days)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
August 30, 2017
Primary Completion (ACTUAL)
November 1, 2018
Study Completion (ACTUAL)
January 23, 2019
Study Registration Dates
First Submitted
April 26, 2017
First Submitted That Met QC Criteria
July 3, 2017
First Posted (ACTUAL)
July 6, 2017
Study Record Updates
Last Update Posted (ACTUAL)
July 20, 2022
Last Update Submitted That Met QC Criteria
July 18, 2022
Last Verified
September 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HTI-1090-101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Advanced Solid Tumors
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AmgenCompletedCancer | Advanced Solid Tumors | Solid Tumors | Tumors | Advanced MalignancyUnited States, Australia
-
NantCell, Inc.CompletedQUILT-2.016: Study of AMG 479 With Biologics or Chemotherapy for Subjects With Advanced Solid TumorsCancer | Advanced Solid Tumors | Solid Tumors | Tumors | Advanced Malignancy
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Incyte CorporationRecruitingA Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid TumorsAdvanced Solid Tumors | Solid Tumors | Metastatic Solid TumorsUnited States, Spain, United Kingdom, France, Italy, Denmark, Switzerland
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Hoffmann-La RocheCompletedSolid Tumors, Advanced Solid TumorsUnited States
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Esperance Pharmaceuticals IncCompletedAdvanced Solid Tumors | Solid TumorsUnited States
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Genentech, Inc.RecruitingAdvanced Solid Tumors | Metastatic Solid TumorsCanada, Korea, Republic of, United States, Brazil, Australia, Argentina, Spain, New Zealand, Poland
-
Millennium Pharmaceuticals, Inc.CompletedAdvanced Solid Tumors, Neoplasms, Advanced SolidHungary
-
Incyte Biosciences Japan GKCompletedAdvanced Solid Tumors | Metastatic Solid TumorsJapan
-
Memorial Sloan Kettering Cancer CenterKyowa Hakko Kirin Pharma, Inc.CompletedAdvanced Solid Tumors | Metastatic Solid TumorsUnited States
-
Bristol-Myers SquibbCompletedAdvanced Solid Tumors | Metastatic Solid TumorsKorea, Republic of, Canada, Australia
Clinical Trials on HTI-1090
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Jiangsu HengRui Medicine Co., Ltd.UnknownSolid Tumor, AdultUnited States
-
Hengrui Therapeutics, Inc.Completed
-
Atridia Pty Ltd.CompletedAdvanced Solid TumorsAustralia
-
National Institute of Allergy and Infectious Diseases...CompletedHIV InfectionsBotswana, United States
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Jiangsu HengRui Medicine Co., Ltd.Unknown
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National Institute of Allergy and Infectious Diseases...Completed
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National Institute of Allergy and Infectious Diseases...CompletedHIV InfectionsUnited States
-
Jiangsu HengRui Medicine Co., Ltd.Completed
-
University of OxfordCompleted
-
Aelix TherapeuticsGilead SciencesCompleted