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TT-10 as a Single Agent in Subjects With Advanced Selected Solid Tumors

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ClinicalTrials.gov Identifier: NCT04969315
Recruitment Status : Not yet recruiting
First Posted : July 20, 2021
Last Update Posted : April 28, 2022
Sponsor:
Information provided by (Responsible Party):
Tarus Therapeutics, Inc.

Brief Summary:
The purpose of this study is to evaluate the safety and tolerability of orally administered TT-10 in subjects with advanced selected solid tumors. The dose escalation portion of the study will determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of TT-10.

Condition or disease Intervention/treatment Phase
Renal Cell Cancer Castrate Resistant Prostate Cancer Non Small Cell Lung Cancer Drug: TT-10 Phase 1 Phase 2

Detailed Description:

Multicenter, open-label dose-escalation Phase I/II clinical study, designed to evaluate the safety, tolerability, PK, PD, anti-tumor activity, and efficacy of TT-10 in subjects diagnosed with advanced Renal cell cancer (RCC), castrate resistant prostate cancer (CRPC) and Non-small cell lung cancer (NSCLC); who have failed or are not eligible for standard of care treatment.

The study will be conducted in two phases. Dose escalation (Phase 1) will be to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D), safety and tolerability of TT-10 in subjects with advanced subjects diagnosed with advanced Renal cell cancer (RCC), castrate resistant prostate cancer (CRPC) and Non-small cell lung cancer (NSCLC); who have failed or are not eligible for standard of care treatment. Dose expansion (Phase 2) will be to further explore the safety and tolerability of the MTD and/or RP2D, PK, PD, anti-tumor activity, and efficacy of TT-10.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II First-in-Human Study of TT-10 as a Single Agent in Subjects With Advanced Selected Solid Tumors
Estimated Study Start Date : August 15, 2022
Estimated Primary Completion Date : June 1, 2023
Estimated Study Completion Date : September 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Multiple Ascending Dose
3+3 Dose escalation until MTD and/or R2PD of TT-10 is determined
Drug: TT-10
TT-10 orally administered BID starting at 10 mg and will be increased to 200 mg (additional dose levels maybe explored, if appropriate based on emerging safety, PK or PD data).




Primary Outcome Measures :
  1. Number of subjects with Dose Limiting Toxicities (DLTs) of TT-10 during the dose escalation phase [ Time Frame: 28 Days ]
    All toxicities will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  2. Define the maximum tolerated dose (MTD) or phase 2 recommended dose of TT-10 during the dose escalation phase [ Time Frame: Up to 1 year ]
  3. Overall Response Rate (ORR) [ Time Frame: From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years) ]
    This is defined as complete response (CR) or PR according to RECIST 1.1 and from the first dose until documented confirmed disease progression.


Secondary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (TEAEs) overall and by severity, seriousness and relatedness. [ Time Frame: Through study completion, an average of 1 year ]
    Safety assessments will be performed on a regular basis using physical examination, spontaneous AE reporting, scheduled and unscheduled laboratory assessments, and other diagnostic evaluations as indicated. Adverse events will be reported using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  2. Duration of Response (DoR) [ Time Frame: From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years) ]
    Time from first confirmed documented objective response (CR or PR) to the date of first confirmed documented objective progression of disease (PD) or death due to any cause whichever occurs first. If a subject has not had an event (PD or death), DR is censored at the date of last adequate tumor assessment.

  3. Progression Free Survival (PFS) [ Time Frame: From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years) ]
    Time from first dose to the date of the first confirmed documented objective progression of disease (PD) or death due to any cause, whichever occurs first.

  4. Peak serum concentration (Cmax) of TT-10 [ Time Frame: From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years) ]
    PK Parameter

  5. Area under the serum concentration versus time curve (AUC) of TT-10 [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose ]
    PK Parameter

  6. Half-life of TT-10 [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose ]
    PK Parameter



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To eligible for inclusion in the dose escalation cohort or expansion cohort 1 in this study, subjects must meet all of the following criteria:

  1. Subjects must be ≥18 years of age.
  2. Subjects or their legal representative must be able to provide written informed consent to participate in the trial prior to the performance of any study-specific procedures.
  3. Diagnosis of histologically or cytologically confirmed advanced selected solid tumors

    • Cohort A dose escalation: Renal cell cancer (RCC), castrate resistant prostate cancer (CRPC) and Non-small cell lung cancer (NSCLC) who have failed or are not eligible for standard of care treatment.
    • Cohort B: Advanced RCC who have failed or are not eligible for standard of care treatment.
    • Cohort C: Advanced CRPC who have failed or are not eligible for standard of care treatment.
    • Cohort D: Advanced NSCLC who have failed or are not eligible for standard of care treatment.
    • Cohort E: Exploratory Biopsy: Inclusive of subjects w/RCC, CRPC and/or NSCLC who have failed or are not eligible for standard of care treatment and have an accessible tumor for pre and post dose biopsies.
  4. ECOG performance status (PS) score 0-1
  5. Have measurable disease per RECIST 1.1 or (for subjects in the expansion cohorts) irRECIST as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  6. Subjects must have locally advanced, recurrent or metastatic neoplastic disease that is not curable by currently available local therapies.
  7. Failure to respond to standard therapy, or for whom no appropriate therapies are available (based on the judgment of the Investigator)
  8. Cohort E Only: Fresh tissue sample obtained prior to treatment initiation and agree to on treatment biopsy from same lesion.
  9. Life expectancy of ≥ 3 months
  10. Subjects must have adequate hematologic function based on the following:

    • Absolute neutrophil count ≥ 1.5 x 109/L
    • Platelet count ≥ 100 x 109/L
    • Hemoglobin ≥ 9.0 g/dL
  11. Subjects must have adequate hepatic function based on the following:

    • Total bilirubin <1.5 × upper limit of normal (ULN) (unless elevated due to Gilbert's syndrome)
    • Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x ULN (≤5 × ULN for subjects with known hepatic metastases)
  12. Subjects must have adequate renal function based on the following:

    • Serum creatinine ≤1.5 × ULN; or
    • Serum creatinine clearance ≥ 45 mL/min (≥ 30 mL/min for subjects), as determined by Cockcroft-Gault equation
  13. Human immunodeficiency virus (HIV) infected subjects must be on antiretroviral therapy (ART) and have a well-controlled HIV infection/disease defined as:

    1. Subjects on ART must have a CD4+ T cell count >350 cells/mm3 at time of screening
    2. Subjects on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening
    3. Subjects on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry (Day 1).
  14. For women of childbearing potential (WCBP): negative urine pregnancy test (UPT) within 1 week before first treatment (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 12 consecutive months for women > 55 years of age). WCBP should be placed on effective birth control directly after testing negative for pregnancy; if not, then WCBP should have a UPT on Day 1 of every cycle, prior to drug administration. Any positive or indeterminant UPT result must be confirmed by Serum.
  15. Female subjects of childbearing potential must use a highly effective mode of contraception or abstain from heterosexual activity for the duration of the trial and for 120 days following the last dose of study medication. A female is NOT of childbearing potential if she has undergone bilateral salpingoophorectomy or is menopausal, defined as an absence of menses for 12 consecutive months. Male subjects must agree to use highly effective contraception.
  16. Ability to adhere to the study visit schedule and all protocol requirements

Exclusion Criteria:

Subjects will be excluded from the study if they satisfy any of the following criteria at the screening visit unless otherwise stated:

Subjects are to be excluded from the study if they meet any of the following criteria:

  1. Major surgery within 4 weeks prior to Screening
  2. Subjects with active central nervous system (CNS) metastases; however, subjects who have undergone radiation and/or surgery for the treatment of CNS metastases, who are neurologically stable, and who are no longer taking pharmacologic doses of corticosteroids are eligible; subjects with leptomeningeal metastases are not eligible.
  3. Has received prior radiotherapy within 2 weeks of start of study treatment. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  4. Primary CNS malignancy
  5. HIV-infected subjects with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
  6. Subjects who are hepatitis B surface antigen positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to enrollment.

    Note: Subjects should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention.

    Hepatitis B screening tests are not required unless:

    • Known history of HBV infection
    • As mandated by local health authority.
  7. Subjects with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening. Note: Subjects must have completed curative antiviral therapy at least 4 weeks prior to enrollment.

    Hepatitis C screening tests are not required unless:

    • Known history of HCV infection
    • As mandated by local health authority.
  8. Subjects who require immunosuppressive therapy including, but not limited to, treatment with corticosteroids in pharmacologic doses (equivalent to ≥10 mg prednisone daily), cyclosporine, mycophenolate, azathioprine, methotrexate, adalimumab, infliximab, vedolizumab, tofacitinib, dupilumab, rituximab, etc. or systemic steroids (except for steroid use as cortisol replacement therapy in documented adrenal insufficiency)
  9. Ongoing systemic bacterial, fungal, or viral infections at Screening

    a. NOTE: Subjects on antimicrobial, antifungal, or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met

  10. Administration of a live vaccine within 6 weeks of first dose of study drug
  11. Baseline QT interval corrected with Fridericia's method (QTcF) > 480 ms (average of triplicate readings)

    a. NOTE: Criterion does not apply to subjects with a right or left bundle branch block.

  12. Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
  13. Female subjects who are pregnant or breastfeeding
  14. Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or prostate intraepithelial neoplasia
  15. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
  16. History of peptic ulcer and/or gastrointestinal bleed within the past 6 months prior to Screening
  17. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months prior to Screening
  18. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the subject associated with his or her participation in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04969315


Locations
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United States, New Jersey
Tarus Therapeutics, Inc.
North Bergen, New Jersey, United States, 07047
Contact: Sushant Kumar, PhD    862-202-9510    skumar@tarustx.com   
Contact: Desa Rae E Pastore, MS    +1716-400-9467    drpastore@tarustx.com   
Sponsors and Collaborators
Tarus Therapeutics, Inc.
Publications:

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Responsible Party: Tarus Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04969315    
Other Study ID Numbers: TT-10-101
First Posted: July 20, 2021    Key Record Dates
Last Update Posted: April 28, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tarus Therapeutics, Inc.:
Failed or not eligible for standard of care
Advanced Selected Solid Tumors
TT-10
Adenosine
Adenosine Antagonist
A2A
A2AR Inhibitor
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Kidney Diseases
Urologic Diseases