Clinical trial NCT06386705: TSN084 Treating Patients With Advanced Malignant Tumors
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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Malignant Neoplasm
Lead sponsor: Tyligand Bioscience (Shanghai) Limited
Sponsor class: INDUSTRY
First posted: 2024-04-26
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose limiting toxicity (DLT)
timeFrame: 28 days
measure: Incidence of Treatment-Emergent Adverse Events (TEAE)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Maximum plasma concentration (Cmax)
timeFrame: 28 days
measure: Time to Cmax (Tmax)
timeFrame: 28 days
measure: Area under the concentration versus time curve from time 0 to the last measurable concentration (AUC 0-t)
timeFrame: 28 days
measure: Objective response rate (ORR)
timeFrame: Up to 3 years
measure: Duration of response (DoR)
timeFrame: Up to 3 years
measure: Disease control rate (DCR)
timeFrame: Up to 3 years
measure: Time to response (TTR)
timeFrame: Up to 3 years
measure: Progression free survival (PFS)
timeFrame: Up to 3 years
measure: Overall survival (OS)
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Peking university cancer hospital
state: Beijing
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Jie Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: