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Advanced Solid TumorsPhase 1NCT03654547

Safety of TT-00420 (Tinengotinib) Monotherapy in Patients With Advanced Solid Tumors and Triple Negative Breast Cancer

A Phase 1 study testing TT-00420 in people with Advanced Solid Tumors and Triple Negative Breast Cancer, run by TransThera Sciences (Nanjing), Inc. at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a first-in-human, phase I clinical research study with TT-00420, an investigational, oral, multi-target, dual mechanism kinase inhibitor targeting both mitosis and tumor micro-environment, for the treatment of triple negative breast cancer (TNBC) and other advanced solid tumors. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
TT-00420
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
2 sitesin 2 countries
Study dates
8 Jan 2019to 28 Feb 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Aged 18 years to 75 years at the time of provision of informed consent
  • Dose Escalation Cohorts: Histopathological or cytologically documented locally advanced or metastatic solid tumors who have no available standard therapeutic treatment options Dose Expansion Cohorts: Histopathological or cytologically documented locally advanced or metastatic TNBC or SATs
  • TNBC Dose Expansion Cohort:
  • Histologically proven invasive breast carcinoma with triple negative receptor status per institutional standard and with confirmed negative for ER and PR by IHC (<10% positive tumor nuclei)
  • relapsed/refractory to at least one line of systemic chemotherapy
  • At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors
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  • ECOG performance status of 0 or 1
  • 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) ≥ 9 g/dl
  • Platelets (plt) ≥ 100 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, or direct bilirubin < ULN for patients with total bilirubin levels >1.5 ULN
  • Serum creatinine ≤ 1.5 x ULN or calculated 24-hour clearance ≥ 50 mL/min
  • Negative pregnancy test within 72 hours before starting study treatment in all pre-menopausal women and women < 12 months after the onset of menopause
  • Must agree to take sufficient contraceptive methods to avoid pregnancy during the study and until at least 6 months after ceasing study treatment
  • Able to sign informed consent and to comply with the protocol

Who cannot join

  • Women who are pregnant or lactating
  • Women of child-bearing potential (WOCBP) who does not use adequate birth control
  • Patients with any hematologic malignancy. This includes leukemia (any form), lymphoma, and multiple myeloma.
  • Patients with
  • a history of primary central nervous system tumors or
  • carcinomatous meningitis Note: Patients with treated brain metastases that are off corticosteroid and have been clinically stable 28 days are eligible for enrollment
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  • Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as result of patient's mood assessment questionnaire:
  • 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
  • The psychiatric judgment, if available, overrules the mood assessment questionnaire result/investigator judgment
  • Impaired cardiac function or clinically significant cardiac diseases, including but not limited to any of the following:
  • LVEF < 45% as determined by MUGA scan or ECHO
  • Congenital long QT syndrome
  • QTc ≥ 450 msec on screening ECG
  • Unstable angina pectoris ≤ 3 months prior to starting study drug
  • Acute myocardial infarction ≤ 3 months prior to starting study drug
  • 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 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  • Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., uncontrolled hypertriglyceridemia [triglycerides > 500 mg/dL], active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
  • 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
  • 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
  • Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated before enrollment, may be continued
  • Patients who are currently receiving treatment with therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants
  • Patients who have received corticosteroids ≤ 2 weeks prior to starting study drug or who have not recovered from the side effects of such treatment
  • Patients who are currently receiving treatment with medication that has known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
  • Patients who are receiving high to moderate CYP3A inhibitors and inducers as listed in Appendix F
  • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
  • Known history of active infection with Hepatitis B (e.g., HBsAg reactive), or Hepatitis C (e.g., HCV RNA (qualitative) is detected)
  • Has received a live-virus vaccination within 30 days of planned first dose Note: Seasonal flu vaccines are permitted.
  • Inability to swallow or tolerate oral medication
  • 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 participation and compliance in the trial

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

  • MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

China1 site

  • Cancer Hopital Chinese Academy of Medical Sciences

    Beijing, Beijing Municipality, 100000

Other trials in China

About this study

Official title: A Phase I, First-In-Human, Multicenter, Open-Label Study of TT-00420, Administered Orally in Adult Patients With Advanced Solid Tumors and Triple Negative Breast Cancers

This is a first-in-human, phase I clinical research study with TT-00420, an investigational, oral, multi-target, dual mechanism kinase inhibitor targeting both mitosis and tumor micro-environment, for the treatment of triple negative breast cancer (TNBC) and other advanced solid tumors. The study consists of a dose escalation part followed by a MTD expansion part.

Read the detailed description

Dose Escalation Cohorts: Eligible adult patients with advanced solid tumors will be enrolled into Dose Escalation cohorts. Starting dose of TT-00420 mono-therapy will be 1 mg p.o., q.d. TT-00420 capsule will be administered once daily on a continuous schedule. A treatment cycle consists of 28 days. An ABLRM guided by the EWOC principle will evaluate the risk of under-dose or over-dose for the dose tested in each cohort and provide the recommendation dose for next cohort. Dose limiting toxicity (DLT) will be evaluated per the pre-defined DLT criteria and managed by the pre-defined rules detailed in the protocol. Maximum Tolerated Dose (MTD) and/or Dose Recommend for Dose Expansion (DRDE) will be determined in Dose Escalation cohorts.

Dose Expansion Cohorts:

TNBC Cohort:

TNBC Dose-Expansion cohort will be opened to enroll the patients with advanced TNBC and evaluate the safety, PK and preliminary efficacy of TT-00420 to identify the optimal biological dose (OBD), when feasible, in patients with advanced TNBC.

SAT Cohort:

A parallel basket SAT Dose Expansion Cohort will be open to enroll patients with selected advanced tumors (SAT) to evaluate the safety, PK and preliminary efficacy of TT-00420 to identify the optimal biological dose (OBD), when feasible, in patients with SATs.

Recruitment in dose expansion cohorts may be put on hold if any significant safety finding(s) that was not observed in dose escalation cohorts is identified. Bayesian modeling will be updated with the new findings to evaluate if the previously determined MTD or DRDE still suitable for further enrollment.

Being tested
TT-00420
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TT-00420Drug

    TT-00420 is an investigational, oral, multi-target, dual mechanism kinase inhibitor targeting both mitosis and tumor microenvironment, for the treatment of triple negative breast cancer (TNBC) and other advanced solid tumors.

    TT-00420 capsule will be administered once daily on a continuous schedule. A treatment cycle consists of 28 days.

    The proposed dosage form for early clinical research is powder filled hard gelatin capsule (PIC) with dosage strengths as of 1 mg, 5 mg and 20 mg.

Study groups in NCT03654547
Study groupRoleWhat they receive
Dose EscalationExperimentalEligible adult patients with advanced solid tumors will be enrolled into Dose Escalation cohorts and treated with TT-00420 at different dose cohorts. Starting dose will be 1 mg p.o., q.d. An ABLRM guided by the EWOC principle will evaluate the risk of under-dose or over-dose for the dose tested in each cohort and provide the recommendation dose for next cohort. Dose Escalation Teleconference will be held after the last evaluable patient complete Cycle 1 treatment in each dose cohort to evaluate DLT, determine MTD and/or DRDE.
Receives: Drug: TT-00420
Dose ExpansionExperimentalA Dose Expansion cohort will be opened to enroll patients with selected advanced solid tumors and evaluate the safety, PK and preliminary efficacy of TT-00420 to determine the recommended phase 2 dose in patients with advanced solid tumors.
Receives: Drug: TT-00420

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) and/or Dose Limiting Toxicity (DLT)

    FIH Dose Finding

    Measured: At the end of Cycle 1 (each cycle is 28 days)

Secondary outcomes (12)

  1. Dose Recommended for Dose Expansion (DRDE)

    Dose Recommended for Dose Expansion

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  2. Optimal Biological Dose (OBD)

    Dose Recommended for Dose Expansion

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  3. Number of Participants With Abnormal Laboratory Values

    Safety and tolerability of TT-00420

    Measured: Up to 30 days from study discontinuation

  4. Number of Participants With Adverse Events That Are Related to Treatment

    Safety and tolerability of TT-00420

    Measured: Up to 30 days from study discontinuation

  5. Peak Plasma Concentration (Cmax) of TT-00420

    PK parameters of TT-00420

    Measured: through study completion, an average of 6 months

  6. Time at which Cmax was first observed (Tmax) of TT-00420

    PK parameters of TT-00420

    Measured: through study completion, an average of 6 months

  7. Half-life (T1/2) of TT-00420

    PK parameters of TT-00420

    Measured: through study completion, an average of 6 months

  8. Objective Response Rate (ORR)

    ORR of TT-00420 in patients with TNBC or SAT treated in Dose Expansion cohorts

    Measured: through study completion, an average of 1 year

  9. Disease Control Rate (DCR)

    DCR of TT-00420 in patients with TNBC or SAT treated in Dose Expansion cohorts

    Measured: through study completion, an average of 1 year

  10. Duration of Response (DOR)

    DOR of TT-00420 in patients with TNBC or SAT treated in Dose Expansion cohorts

    Measured: through study completion, an average of 1 year

  11. Progression Free Survival (PFS)

    PFS of TT-00420 in patients with TNBC or SAT treated in Dose Expansion cohorts

    Measured: through study completion, an average of 1 year

  12. Overall Survival (OS)

    OS of TT-00420 in patients with TNBC or SAT treated in Dose Expansion cohorts

    Measured: through study completion, an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2018
  2. Study start8 Jan 2019
  3. Primary completion31 Jan 2023
  4. Study completion28 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Dose Escalation arm followed by Dose Expansion arm
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03654547
Sponsor's protocol ID
TT420X2101
Status last verified
Jul 2025
First submitted
21 Aug 2018
Last updated
24 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Peng P, Qiang X, Li G, Li L, Ni S, Yu Q, Sourd L, Marangoni E, Hu C, Wang D, Wu D, Wu F. Tinengotinib (TT-00420), a Novel Spectrum-Selective Small-Molecule Kinase Inhibitor, Is Highly Active Against Triple-Negative Breast Cancer. Mol Cancer Ther. 2023 Feb 1;22(2):205-214. doi: 10.1158/1535-7163.MCT-22-0012.

    PubMed 36223547

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TT-00420 in people with Advanced Solid Tumors and Triple Negative Breast Cancer, run by TransThera Sciences (Nanjing), Inc. at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) and/or Dose Limiting Toxicity (DLT) (time frame: At the end of Cycle 1 (each cycle is 28 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03654547, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2025.

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