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

NCT03654547 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: TT420X2101
• Study Type: interventional
• Target: 48
• Locations: 2 countries
• Sites: 2

Brief 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. The study consists of a dose escalation part followed by a MTD expansion part.

Conditions

Advanced Solid Tumors; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

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

  FIH Dose Finding

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

Secondary Outcomes (12)

• Dose Recommended for Dose Expansion (DRDE)

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

• Optimal Biological Dose (OBD)

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

• Number of Participants With Abnormal Laboratory Values

  Up to 30 days from study discontinuation

• Number of Participants With Adverse Events That Are Related to Treatment

  Up to 30 days from study discontinuation

• Peak Plasma Concentration (Cmax) of TT-00420

  through study completion, an average of 6 months

Other Outcomes (1)

• Exploratory Biomarker Assay

  through study completion, an average of 6 months

Study Arms (2)

Dose Escalation

EXPERIMENTAL

Eligible 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.

Drug: TT-00420

Dose Expansion

EXPERIMENTAL

A 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.

Drug: TT-00420

Interventions

TT-00420 DRUG

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.

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• TransThera Sciences (Nanjing), Inc.: lead

Study Sites (2)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Cancer Hopital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100000, China

Location

Related Publications (1)

• 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.

  PMID: 36223547 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Sarina A. Piha-Paul, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Dose Escalation arm followed by Dose Expansion arm

Study Record Dates

• First Submitted: August 21, 2018
• First Posted: August 31, 2018
• Study Start: January 8, 2019
• Primary Completion: January 31, 2023
• Study Completion: February 28, 2024
• Last Updated: July 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); CN (1)