TSN084 Treating Patients With Advanced Malignant Tumors

A Multicenter, Open-label, Phase Ia/Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of TSN084 Tablets in Patients With Advanced Malignant Tumors.

TSN084 is a novel type II kinase inhibitor with demonstrated anti-tumor effects in vitro and in vivo and targets multiple tyrosine kinases, such as c-MET, FLT3, TRK and serine/threonine kinase CDK8/19. This phase 1a/1b study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of TSN084 in advanced or metastatic malignancies in China.

Study Overview

• Status: Recruiting
• Conditions: Malignant Neoplasm
• Intervention / Treatment: Drug: TSN084

Detailed Description

The phase 1a part will begin with an exploration of TSN084 dose and regimen to determine the maximum tolerated dose (MTD) and/or recommended dose for further investigation (i.e., RP2D). In Phase 1b part, separate cohorts of patients with different histological diagnosis will be evaluated for the clinical activity and efficacy of TSN084 at the recommended dose.

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Tyligand Clinical Trial Info; Phone Number: +86-021-50720081; Email: clinical_trial@tyligand.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Peking University Cancer Hospital
      • Contact: Minglei Zhuo, MD
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Contact: Jie Wang, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men or women ≥18 years old.
• The subject fully understands the requirements of the study and voluntarily signs the written informed consent.
• Be able to comply with the medication requirements of the study and all study related procedures and evaluations; not deemed as potentially unreliable and/or uncooperative.
• Meeting the requirements of tumor types shown below. Phase Ia Study: Histological or cytological diagnosis of locally advanced, relapsed, or metastatic malignancies, not amenable to standard therapy or for which no standard therapy is available.

Phase Ib study: Histological or cytological diagnosis of the locally advanced, relapsed, or metastatic selected malignancies not amenable to standard therapy (disease progression or intolerance), or unable to receive standard therapy/no standard therapy is available. Malignancies with targeted mutations are preferred, including but not limited to MET exon 14 skipping mutation and MET amplification.

• Survival expectations are ≥ 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 for Phase Ia, while 0 to 2 for Phase Ib.
• Patients with adequate organ function at the time of screening.
• Male and female patients of childbearing potential must agree to use effective methods of contraception.

Exclusion Criteria:

• Patients with active brain metastases, except that their central nervous system (CNS) tumor metastases are confined to the supratentorial or cerebellum, have been adequately treated (surgery or radiotherapy), have maintained radiographic stability for at least 4 weeks, and do not require corticosteroids to control symptoms.
• Other malignancies (other than non-melanoma basal cell carcinoma or squamous cell carcinoma of the skin, breast/cervical carcinoma in situ, superficial bladder carcinoma that have received radical treatment and no evidence of disease recurrence) within 5 years prior to initiation of TSN084 treatment;
• Any arterial thromboembolic event, including myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack, occurred within 6 months prior to enrolment;
• Uncontrolled third space effusion requiring repeated drainage, such as pleural effusion, ascites, pericardial effusion, etc. (Patients who do not need drainage effusion or have no significant increase in effusion after 3 days of cessation of drainage can be included).
• Has active gastrointestinal disease or other disease, or other factors such as surgical resection that may significantly affect drug absorption, metabolism, or excretion.
• Pregnant or lactating women.
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
• HIV infected patients (HIV 1/2 antibody positive).
• Known active syphilis infection, or active tuberculosis.
• A history of drug abuse or drug use.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Phase 1a; Dose Escalation/Evaluation	Drug: TSN084; TSN084 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity.
Experimental: Experimental: Phase 1b; TSN084 recommended Phase 2 dose administered to separate cohorts of patients with selected malignancies harboring mutations including but not limited to MET exon14 skipping mutation and MET amplification.	Drug: TSN084; TSN084 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity (DLT)	Number of patients with dose limiting toxicity, to determine the MTD and/or RP2D	28 days
Incidence of Treatment-Emergent Adverse Events (TEAE)	Incidence of TEAE, Serious Adverse Event (SAE), their relationship with the investigational product and severity. Adverse events will be graded according to NCI-CTCAE V5.0.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)		Up to 3 years
Maximum plasma concentration (Cmax)	To characterize the pharmacokinetic (PK) properties of TSN084 in patients with advanced malignant tumors.	28 days
Time to Cmax (Tmax)	To characterize the pharmacokinetic (PK) properties of TSN084 in patients with advanced malignant tumors.	28 days
Area under the concentration versus time curve from time 0 to the last measurable concentration (AUC 0-t)	To characterize the pharmacokinetic (PK) properties of TSN084 in patients with advanced malignant tumors.	28 days
Objective response rate (ORR)	Tumor response assessments by RECIST v1.1	Up to 3 years
Duration of response (DoR)	Tumor response assessments by RECIST v1.1	Up to 3 years
Disease control rate (DCR)	Tumor response assessments by RECIST v1.1	Up to 3 years
Time to response (TTR)	Tumor response assessments by RECIST v1.1	Up to 3 years
Progression free survival (PFS)	Tumor response assessments by RECIST v1.1	Up to 3 years

Collaborators and Investigators

• Sponsor: Tyligand Bioscience (Shanghai) Limited
• Investigators: Principal Investigator: Jie Wang, MD, PhD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2022
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: April 23, 2024
• First Posted (Actual): April 26, 2024

Study Record Updates

• Last Update Posted (Actual): July 29, 2024
• Last Update Submitted That Met QC Criteria: July 25, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TSN084-101CH

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No