NCT03654547

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

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (actual)
• Sponsor: TransThera Sciences (Nanjing), Inc. · Industry
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Advanced Solid Tumors
• Triple Negative Breast Cancer

Interventions

Type	Name	Description
DRUG	TT-00420	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.

Timeline

• Start date: 2019-01-08
• Primary completion: 2023-01-31
• Completion: 2024-02-28
• First posted: 2018-08-31
• Last updated: 2025-07-24

Locations

2 sites across 2 countries: United States, China

Regulatory

• FDA-regulated drug study