Cancer (With or Without Metastasis)Phase 1NCT05300438

Phase I Study of TSN084 in Patients With Advanced Malignant Tumors.

A Phase 1 study testing TSN084 in people with Cancer (With or Without Metastasis), run by Tyligand Bioscience (Shanghai) Limited at 1 site in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Cancer (With or Without Metastasis)
What is being tested?: TSN084
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 74 participants
Where: 1 siteUnited States
Study dates: 18 Feb 2022to Jun 2025
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Men or women ≥18 years old.
The following three points are evaluated by the investigator and are deemed suitable to participate in the study: A. The subject fully understands the requirements of the study and voluntarily signs the written informed consent; B. Be able to comply with the medication requirements of the study and all study related procedures and evaluations; C. 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 malignancies not amenable to standard therapy or for which no standard therapy is available. The specific tumor types/basket design with specific driven gene(s) will be determined by the principal investigator and the sponsor based on the Phase Ia study result.
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. Subjects with advanced or metastatic malignancies who had at least one evaluable lesion during phase Ia study, while at least one measurable lesion during phase Ib study according to RECIST V1.1.
Patients with adequate organ function at the time of screening (requiring no blood transfusion, no use of hematopoietic stimulating factor or human albumin within 14 days prior to screening), specifically defined as:

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Blood routine: Absolute neutrophil count (ANC) ≥ 1.5×109/L; Platelet count (PLT) ≥100×109/L; Hemoglobin (HGB) ≥ 90 g/L;
Liver function: Serum Total bilirubin (TBIL) ≤ 1.5 Upper limit of normal value (ULN), and serum TBIL≤ 3×ULN in patients with liver metastasis or confirmed Gilbert syndrome. Alanine aminotransferase (ALT) and Aspartate transferase (AST) ≤ 2.5×ULN in subjects without liver metastasis; ALT or AST≤ 5×ULN in subjects with liver metastasis;
Renal function: estimated creatinine clearance (CLcr) ≥ 60 mL/min as calculated using Cockcroft-Gault formula (Cockcroft DW 1976);
Coagulation function: Activated Partial thromboplastin Time (APTT) and international normalized ratio (INR) ≤ 1.5×ULN (or within target range if on anticoagulation therapy);
Cardiac function: Echocardiography (ECHO) shows left ventricular ejection fraction (LVEF) > 50%.
Serum pregnancy test (for female of childbearing potential) negative within 3 days prior to first dosing of study treatment. Male and female patients of childbearing potential must agree to use effective methods of contraception from the time of first negative pregnancy test at screening, throughout the study and for 6 months after the last dose of the investigational product. A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.

Who cannot join

Has received any investigational agents within 21 days prior to the first administration of TSN084; or have stopped any investigational agents or other anti-tumors drugs for less than 5 half-lives or 21 days, whichever is longer;
Acute toxic effects of prior anti-tumor therapy have not recovered to clinically significant NCI-CTCAE V5.0 grade ≤1 toxicity or baseline prior to the first administration of TSN084.
At rest, the average Corrected QT interval (QTc, Fridericia's correction formula used) obtained by 12-lead Electrocardiograph (ECG) examination is > 470 ms (repeated 3 times). A variety of clinically significant arrhythmia, conduction, and resting ECG abnormalities, such as complete left bundle branch block, degree III, degree II, PR interval >250 ms. Various factors that may increase the risk of prolonged QTc or arrhythmia events, such as heart failure, hypokalemia, congenital long QT syndrome, a family history of long QT syndrome in a direct family member or sudden unexplained death before age 40, and use of any medications known to prolong QT intervals.
Has an acute or chronic active hepatitis B defined as hepatitis B virus (HBV) DNA copy number ≥1×103 copies/mL or ≥ 200 IU/ml.
Has acute or chronic active hepatitis C (HCV) defined as HCV-RNA level greater than the upper limit of the central reference value.
Patients with active brain metastases will be allowed to enroll if 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.

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Concurrent diseases that have not been controlled, such as:
Severe infection, including but not limited to hospitalization due to infection, bacteremia, or severe pneumonia complications, occurs within 4 weeks prior to initiation of study treatment; Or patients who received therapeutic oral or intravenous antibiotics within two weeks prior to starting study treatment, and who received prophylactic antibiotics (e.g., for the prevention of urinary tract infection or chronic obstructive pulmonary disease);
Symptomatic congestive heart failure (New York Heart Association Grades II-IV) or symptomatic or poorly controlled arrhythmias;
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;
Suspicion or confirmation of acute promyelocytic leukemia (for patients with acute myeloid leukemia) based on morphology, immune typing, molecular detection, or chromosome karyotype;
Current subjects with cancerous meningitis, spinal cord compression, etc.;
A history of poorly controlled hypertension;
Symptomatic endogenous pulmonary disease;
Any arterial thromboembolic event, including myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack, occurred within 6 months prior to enrolment;
Significant malnutrition, such as the need for intravenous nutrient supplementation. Those who were stable for more than 4 weeks after correction of malnutrition before treatment of first dose of investigational product could be included.
Tumor invasion of surrounding important organs or blood vessels (such as mediastinal great vessels, superior vena cava, trachea, esophagus, etc.), or at risk of esophagotracheal fistula or esophagopleural fistula;
After endoesophageal or tracheal stent implantation;
Other acute or chronic diseases or laboratory test abnormalities that may increase the risks associated with study participation or investigational product administration, or interfere with the interpretation of study results and, in the investigator's judgment, make subjects ineligible for study participation;
Has a history of gastrointestinal perforation and/or fistula 6 months prior to the study enrollment;
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).
Expected to receive other anti-tumor therapies during the study (palliative radiotherapy is allowed).
Allergic to TSN084 or its components.
Has active gastrointestinal disease or other disease, or other factors such as surgical resection that may significantly affect drug absorption, metabolism, or excretion. This includes but not limited to the following conditions: malabsorption syndrome, inflammatory bowel disease, partial or complete intestinal obstruction, gastric or small intestinal resection.
Has severe lung disease or history, such as moderate to severe chronic obstructive pulmonary disease (COPD), history of interstitial lung disease (ILD), drug-induced ILD, acute or chronic infectious pneumonia, lung transplantation, etc.
Use of strong inducers or inhibitors of CYP3A drugs.
Pregnant or lactating women.
Dysphagia.
Being involved in another interventional clinical study, or in an observational (non-interventional) clinical study, or in the follow-up phase of an interventional study.
Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
Had a major surgical procedure (craniotomy, thoracotomy, laparotomy, vascular intervention, as defined by the investigator) within 4 weeks prior to the first administration of the investigational product, or had an unhealed wound, ulcer, or fracture. Note: For palliative care purposes, local surgical treatment of isolated lesions is acceptable.
HIV infected patients (HIV 1/2 antibody positive).
Known active syphilis infection, or active tuberculosis.
Has a clear history of mental disorder with ongoing treatment.
A history of drug abuse or drug use.
The investigator believes that the subject may have other factors that may affect the results of the study and interfere with the subject's participation in the entire study process, including previous or existing physical conditions, abnormal treatment or laboratory tests, and the subject's unwillingness to comply with all procedures, restrictions and requirements of the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

MD Anderson Cancer Center
Houston, Texas, 77030

Other trials in United States

About this study

Official title: 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 protein 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 first-in-human 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.

Conditions: Cancer (With or Without Metastasis)
Being tested: TSN084
Medical subject headings: Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TSN084Drug
Oral tablets

Study groups in NCT05300438
Study group	Role	What they receive
TSN084	Experimental	Not described Receives: Drug: TSN084

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of patients with dose limiting toxicity
Number of patients with dose limiting toxicity.
Measured: Every subject's DLT observation window is 28 days.
Incidence of Treatment-Emergent Adverse Events
Incidence of adverse events, Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE), their relationship with the investigational product and respective severity. Adverse events and laboratory test values will be graded according to NCI-CTCAE V5.0.
Measured: From first dose to 28 ±7 days after last dose

Secondary outcomes (6)

Maximum plasma concentration (Cmax)
To characterize the pharmacokinetic (PK) properties of TSN084 in patients with advanced malignant tumors.
Measured: From first dose to day 1 in the second 28-day cycle
Time to Cmax (Tmax)
To characterize the pharmacokinetic (PK) properties of TSN084 in patients with advanced malignant tumors.
Measured: From first dose to day 1 in the second 28-day cycle
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.
Measured: From first dose to day 1 in the second 28-day cycle
Objective response rate (ORR) defined as the proportion of patients who have a CR or PR
Tumor response assessments by the corresponding criteria by RECIST v1.1 to assess Objective response rate (ORR)
Measured: From first dose to within 3 days of last dose.
Duration of response (DoR)
Tumor response assessments by the corresponding criteria by RECIST v1.1 to assess Duration of response (DoR).
Measured: From first dose to within 3 days of last dose.
Disease control rate (DCR)
Tumor response assessments by the corresponding criteria by RECIST v1.1 to assess Disease control rate (DCR) after the study treatment.
Measured: From first dose to within 3 days of last dose.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Feb 2022Jun 2025

First posted29 Mar 2022
Study start18 Feb 2022
Primary completionMar 2025 (estimated)
Study completionJun 2025 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Cancer (With or Without Metastasis)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 74 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05300438
Sponsor's protocol ID: TSN084-101US
Status last verified: Jun 2024
First submitted: 8 Mar 2022
Last updated: 25 Jun 2024
Results posted: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 25 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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.
ClinicalTrials.gov ID: NCT05300438
Acronym / sponsor ID: TSN084-101US
Conditions: Cancer (With or Without Metastasis)
Phase: Phase 1
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 74 participants (estimated)
Lead sponsor: Tyligand Bioscience (Shanghai) LimitedIndustry (pharma, biotech, devices)
Study start: 18 Feb 2022 (actual)
Primary completion: Mar 2025 (estimated)
Study completion: Jun 2025 (estimated)
First posted: 29 Mar 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
TSN084	Experimental	Drug: TSN084

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Men or women ≥18 years old.
The following three points are evaluated by the investigator and are deemed suitable to participate in the study: A. The subject fully understands the requirements of the study and voluntarily signs the written informed consent; B. Be able to comply with the medication requirements of the study and all study related procedures and evaluations; C. 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 malignancies not amenable to standard therapy or for which no standard therapy is available. The specific tumor types/basket design with specific driven gene(s) will be determined by the principal investigator and the sponsor based on the Phase Ia study result.
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. Subjects with advanced or metastatic malignancies who had at least one evaluable lesion during phase Ia study, while at least one measurable lesion during phase Ib study according to RECIST V1.1.

Key exclusion criteria (36 listed)

Has received any investigational agents within 21 days prior to the first administration of TSN084; or have stopped any investigational agents or other anti-tumors drugs for less than 5 half-lives or 21 days, whichever is longer;
Acute toxic effects of prior anti-tumor therapy have not recovered to clinically significant NCI-CTCAE V5.0 grade ≤1 toxicity or baseline prior to the first administration of TSN084.
At rest, the average Corrected QT interval (QTc, Fridericia's correction formula used) obtained by 12-lead Electrocardiograph (ECG) examination is > 470 ms (repeated 3 times). A variety of clinically significant arrhythmia, conduction, and resting ECG abnormalities, such as complete left bundle branch block, degree III, degree II, PR interval >250 ms. Various factors that may increase the risk of prolonged QTc or arrhythmia events, such as heart failure, hypokalemia, congenital long QT syndrome, a family history of long QT syndrome in a direct family member or sudden unexplained death before age 40, and use of any medications known to prolong QT intervals.
Has an acute or chronic active hepatitis B defined as hepatitis B virus (HBV) DNA copy number ≥1×103 copies/mL or ≥ 200 IU/ml.
Has acute or chronic active hepatitis C (HCV) defined as HCV-RNA level greater than the upper limit of the central reference value.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TSN084Oral tablets	Drug	TSN084

Primary outcome

Number of patients with dose limiting toxicity
Time frame: Every subject's DLT observation window is 28 days.
Number of patients with dose limiting toxicity.
Incidence of Treatment-Emergent Adverse Events
Time frame: From first dose to 28 ±7 days after last dose
Incidence of adverse events, Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE), their relationship with the investigational product and respective severity. Adverse events and laboratory test values will be graded according to NCI-CTCAE V5.0.

6 secondary outcomes

Maximum plasma concentration (Cmax)
Time frame: From first dose to day 1 in the second 28-day cycle
Time to Cmax (Tmax)
Time frame: From first dose to day 1 in the second 28-day cycle
Area under the concentration versus time curve from time 0 to the last measurable concentration (AUC 0-t)
Time frame: From first dose to day 1 in the second 28-day cycle
Objective response rate (ORR) defined as the proportion of patients who have a CR or PR
Time frame: From first dose to within 3 days of last dose.
Duration of response (DoR)
Time frame: From first dose to within 3 days of last dose.
Disease control rate (DCR)
Time frame: From first dose to within 3 days of last dose.

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2024.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Siqing Fu, MD, PhD principal investigator

M.D. Anderson Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TSN084 in people with Cancer (With or Without Metastasis), run by Tyligand Bioscience (Shanghai) Limited at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 25 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of patients with dose limiting toxicity (time frame: Every subject's DLT observation window is 28 days.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05300438.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2024.