TSN084 Treating Patients With Advanced Malignant Tumors

July 25, 2024 updated by: Tyligand Bioscience (Shanghai) Limited

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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
114

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dose limiting toxicity (DLT)
Time Frame: 28 days
Number of patients with dose limiting toxicity, to determine the MTD and/or RP2D
28 days
Incidence of Treatment-Emergent Adverse Events (TEAE)
Time Frame: Up to 3 years
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: Up to 3 years
Up to 3 years
Maximum plasma concentration (Cmax)
Time Frame: 28 days
To characterize the pharmacokinetic (PK) properties of TSN084 in patients with advanced malignant tumors.
28 days
Time to Cmax (Tmax)
Time Frame: 28 days
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)
Time Frame: 28 days
To characterize the pharmacokinetic (PK) properties of TSN084 in patients with advanced malignant tumors.
28 days
Objective response rate (ORR)
Time Frame: Up to 3 years
Tumor response assessments by RECIST v1.1
Up to 3 years
Duration of response (DoR)
Time Frame: Up to 3 years
Tumor response assessments by RECIST v1.1
Up to 3 years
Disease control rate (DCR)
Time Frame: Up to 3 years
Tumor response assessments by RECIST v1.1
Up to 3 years
Time to response (TTR)
Time Frame: Up to 3 years
Tumor response assessments by RECIST v1.1
Up to 3 years
Progression free survival (PFS)
Time Frame: Up to 3 years
Tumor response assessments by RECIST v1.1
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tyligand Bioscience (Shanghai) Limited

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jie Wang, MD, PhD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 20, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 23, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 23, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 26, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 29, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 25, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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