Study of TT-00420 (Tinengotinib) Tablet as Monotherapy and Combination Therapy in Patients With Advanced Solid Tumors

December 28, 2023 updated by: TransThera Sciences (Nanjing), Inc.

A Phase Ib/II, Multicenter, Open-Label Study of TT-00420 Tablet, as Monotherapy or in Combination Regimens, in Patients With Advanced Solid Tumors

This is a Phase Ib/II, multicenter, open-label study to evaluate the safety and preliminary efficacy of TT-00420 tablet, as monotherapy or in combination regimens, in patients with advanced solid tumors.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Study consists of three arms, Arm A is a Phase Ib/II study of TT-00420 tablet monotherapy, Arm B is a Phase Ib/II study of TT-00420 tablet in combination with nab-paclitaxel (Abraxane®) and Arm C is a PK run-in study of TT-00420 tablet.

Arm A: TT-00420 Tablet Monotherapy Phase Ib will enroll patients with preferred indications including metastatic cholangiocarcinoma, HER2-negative breast cancer including TNBC, bladder cancer, small cell lung cancer, prostate cancer, thyroid cancer, sarcoma, gastric cancer, gallbladder cancer and other advanced solid tumors to receive TT-00420 monotherapy. Based on preliminary efficacy results, Phase II will enroll additional patients in select indications to evaluate the efficacy of TT-00420 monotherapy.

Arm B: TT-00420 tablet in combination with nab-paclitaxel (Abraxane®) Arm B will enroll patients with metastatic HER2-negative breast cancers, including triple-negative breast cancer (TNBC). Phase Ib will be a dose escalation study of TT-00420 in combination with nab-paclitaxel, guided by 3+3 design, to determine a Recommended Phase 2 Dose (RP2D). Phase II will enroll additional patients with metastatic HER2-negative breast cancers to further evaluate the efficacy of the combination regimen.

Arm C: PK Run-in Study of TT-00420 Tablet Arm C will enroll patients with preferred indications including cholangiocarcinoma, TNBC/HER2- negative breast cancer, prostate cancer, sarcoma, hepatocellular carcinoma (HCC), bladder cancer, small cell lung cancer, thyroid cancer, gastric cancer, gallbladder cancer and other advanced solid tumors to receive TT-00420 monotherapy administered as once daily (q.d.) or twice daily (b.i.d.).

Study Type

Interventional

Enrollment (Estimated)

225

Phase

  • Phase 2
  • 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 Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University of Chicago
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Rutgers Cancer Institute
    • Ohio
      • Canton, Ohio, United States, 44718
        • Gabrail Cancer Center Research
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

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

Description

Inclusion Criteria:

  1. ≥ 18 years of age
  2. Histopathological or cytologically documented locally advanced or metastatic solid tumors who have no available standard therapeutic treatment options
  3. At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

  5. Adequate organ function confirmed at screening and within 10 days of initiating treatment, as evidenced by:

    • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
    • Hemoglobin (Hgb) ≥ 8 g/dl
    • Platelets (plt) ≥ 75 x 10^9/L
    • AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastases are present
    • Total bilirubin ≤ 1.5 x ULN
    • Calculated creatinine clearance ≥ 50 mL/min (Cockcroft Gault formula)
  6. Negative pregnancy test within 72 hours before starting study treatment in all premenopausal women and women < 12 months after the onset of menopause
  7. Must agree to take sufficient contraceptive methods to avoid pregnancy during the study and until at least 6 months after ceasing study treatment
  8. Able to sign informed consent and comply with the protocol

Exclusion Criteria:

  1. Women who are pregnant or lactating
  2. Women of child-bearing potential (WOCBP) who do not use adequate birth control
  3. Patients with any hematologic malignancy, including leukemia (any form), lymphoma, and multiple myeloma
  4. Patients with a history of primary central nervous system tumors or carcinomatous meningitis.

  5. Patients with the following mood disorders as judged by the Investigator or a psychiatrist:

    • Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia; a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
    • ≥ CTCAE grade 3 anxiety

  6. Impaired cardiac function or significant diseases, including but not limited to any of the following:

    • left ventricular ejection fraction (LVEF) < 45% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO)
    • Congenital long QT syndrome
    • QTcF ≥ 480 msec on screening ECG
    • Unstable angina pectoris ≤ 3 months prior to starting study drug
    • Acute myocardial infarction ≤ 3 months prior to starting study drug

  7. Patients with:

    • unresolved diarrhea ≥ CTCAE grade 2, or
    • impairment of gastrointestinal (GI) function, or
    • GI disease that may significantly alter the absorption of TT-00420
  8. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., uncontrolled hypertension, uncontrolled hypertriglyceridemia, or active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
  9. Patients who have received chemotherapy, targeted therapy, or immunotherapy ≤ 4 weeks (6 weeks for nitrosourea or mitomycin-C) prior to starting study drug or who have not recovered from side effects of such therapy
  10. Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  11. Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  12. Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤ 4 weeks prior to starting study drug.
  13. Patients who are currently receiving treatment with therapeutic doses of warfarin sodium or any other coumarin-derivative anticoagulants
  14. Patients who have received systemic corticosteroids ≤ 2 weeks prior to starting study drug or who have not recovered from the side effects of such treatment.
  15. Patients who are currently receiving treatment with strong CYP3A inhibitors or inducers ≤ 2 weeks prior to starting study drug.
  16. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory; patients with well controlled HIV might be enrolled)
  17. Known history of active infection with Hepatitis B or Hepatitis C
  18. Has received a live-virus vaccination within 30 days of planned first dose
  19. Inability to swallow or tolerate oral medication
  20. Has a history or current evidence of any condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might confound the results of the trial, interfere with the patient's safe participation and compliance in the trial.

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 Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Monotherapy Cohorts
TT-00420 tablets will be administered once daily in 28-day cycles.
Drug: TT-00420
TT-00420 tablet will be administered orally once daily per protocol defined schedule.
Experimental: Dose Escalation Cohorts (Combination Therapy)
TT-00420 tablets will be administered once daily in 28-day cycles. Nab-paclitaxel 100 mg/m^2 will be administered intravenously on Day 1, 8, and 15 of each 28-day cycle. Dose escalation will be guided by a 3+3 design in Phase Ib to determine the recommended phase 2 dose (RP2D).
Drug: TT-00420
TT-00420 tablet will be administered orally once daily per protocol defined schedule.
Combination product: Nab-Paclitaxel
Nab-Paclitaxel would be administered via infusion on Day 1,8, and 15 of 28-day cycle
Experimental: PK Run-in Cohorts
TT-00420 tablets will be administered once or twice daily in 28-day cycles according to assigned cohort.
Drug: TT-00420
TT-00420 tablet will be administered orally once daily per protocol defined schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Time Frame: Up to 30 days from study discontinuation
As assessed per NCI Common Toxicity Criteria for Adverse Events, version 5.0
Up to 30 days from study discontinuation
Dose limiting toxicity (DLT)
Time Frame: Up to 28 days from the first dose
Dose escalation cohorts are monitored and assessed using the NCI Common Toxicity Criteria for Adverse Events, version 5.0.
Up to 28 days from the first dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Through study completion, an average of 9 months.
The proportion of subjects who achieved a complete response (CR) or a partial response (PR) based on RECIST version 1.1.
Through study completion, an average of 9 months.
Disease Control Rate (DCR)
Time Frame: Through study completion, an average of 9 months.
Defined as CR + PR + stable disease (SD) based on RECIST version 1.1.
Through study completion, an average of 9 months.
Duration of Objective Response (DOR)
Time Frame: Through study completion, an average of 9 months.
Duration of response for CR or PR based on RECIST version 1.1.
Through study completion, an average of 9 months.
Progression Free Survival (PFS)
Time Frame: From first study drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
From first study drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Overall Survival (OS)
Time Frame: From first study drug administration until the date of death from any cause, assessed up to 24 months
From first study drug administration until the date of death from any cause, assessed up to 24 months
Area under the curve (AUC0-∞)
Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.
From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Area under the curve (AUC0-t)
Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.
From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Maximum observed concentration (Cmax)
Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.
From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Half-life (T1/2)
Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Time to Maximum Concentration (Tmax)
Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Volume of Distribution (Vd)
Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genetic Alteration Status
Time Frame: Through study completion, an average of 9 months
Evaluation of biomarkers, including but not limited to, fibroblast growth factor receptor (FGFR) mutation status
Through study completion, an average of 9 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

TransThera Sciences (Nanjing), Inc.

Investigators

  • Principal Investigator: Sarina A. Piha-Paul, MD, M.D. Anderson Cancer Center

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)

March 14, 2021

Primary Completion (Estimated)

February 1, 2024

Study Completion (Estimated)

February 1, 2024

Study Registration Dates

First Submitted

February 2, 2021

First Submitted That Met QC Criteria

February 2, 2021

First Posted (Actual)

February 8, 2021

Study Record Updates

Last Update Posted (Estimated)

January 3, 2024

Last Update Submitted That Met QC Criteria

December 28, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TT420X1103

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.

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