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

NCT04742959 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: TT420X1103
• Study Type: interventional
• Target: 203
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Advanced Solid Tumor; Cholangiocarcinoma; HER2-negative Breast Cancer; Triple Negative Breast Cancer; Bladder Cancer; Small-cell Lung Cancer; Prostate Cancer; Thyroid Cancer; Sarcoma; Gastric Cancer; Gallbladder Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

  As assessed per NCI Common Toxicity Criteria for Adverse Events, version 5.0

  Up to 30 days from study discontinuation

• Dose limiting toxicity (DLT)

  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 Outcomes (11)

• Objective Response Rate (ORR)

  Through study completion, an average of 9 months.

• Disease Control Rate (DCR)

  Through study completion, an average of 9 months.

• Duration of Objective Response (DOR)

  Through study completion, an average of 9 months.

• Progression Free Survival (PFS)

  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)

  From first study drug administration until the date of death from any cause, assessed up to 24 months

Other Outcomes (1)

• Genetic Alteration Status

  Through study completion, an average of 9 months

Study Arms (3)

Monotherapy Cohorts

EXPERIMENTAL

TT-00420 tablets will be administered once daily in 28-day cycles.

Drug: TT-00420

Dose Escalation Cohorts (Combination Therapy)

EXPERIMENTAL

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; Combination Product: Nab-Paclitaxel

PK Run-in Cohorts

EXPERIMENTAL

TT-00420 tablets will be administered once or twice daily in 28-day cycles according to assigned cohort.

Drug: TT-00420

Interventions

TT-00420 DRUG

TT-00420 tablet will be administered orally once daily per protocol defined schedule.

Dose Escalation Cohorts (Combination Therapy); Monotherapy Cohorts; PK Run-in Cohorts

Nab-Paclitaxel COMBINATION_PRODUCT

Nab-Paclitaxel would be administered via infusion on Day 1,8, and 15 of 28-day cycle

Dose Escalation Cohorts (Combination Therapy)

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age
• Histopathological or cytologically documented locally advanced or metastatic solid tumors who have no available standard therapeutic treatment options
• At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors
• Eastern Cooperative Oncology Group (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) ≥ 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)
• Negative pregnancy test within 72 hours before starting study treatment in all premenopausal 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 comply with the protocol

You may not qualify if:

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

Sponsors & Collaborators

• TransThera Sciences (Nanjing), Inc.: lead

Study Sites (6)

City of Hope

Duarte, California, 91010, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Rutgers Cancer Institute

New Brunswick, New Jersey, 08901, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Cholangiocarcinoma; Triple Negative Breast Neoplasms; Urinary Bladder Neoplasms; Small Cell Lung Carcinoma; Prostatic Neoplasms; Thyroid Neoplasms; Sarcoma; Stomach Neoplasms; Gallbladder Neoplasms

Interventions

130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Breast Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Genital Diseases; Prostatic Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Neoplasms, Connective and Soft Tissue; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Biliary Tract Neoplasms; Biliary Tract Diseases; Gallbladder 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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: Study will consist of three arms: Arm A (TT-00420 Tablet Monotherapy), Arm B (TT-00420 tablet in combination with nab-paclitaxel (Abraxane®)) and Arm C (PK Run-in Study of TT-00420 Tablet).

Study Record Dates

• First Submitted: February 2, 2021
• First Posted: February 8, 2021
• Study Start: March 14, 2021
• Primary Completion: February 20, 2024
• Study Completion: February 20, 2024
• Last Updated: April 26, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)