A Study to Evaluate the Efficacy and Safety of TL118 in Solid Tumors Patients

Study Overview
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Brief Summary
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The main objective of the study will be to evaluate the efficacy of TL118 in participants with solid tumors harboring NTRK gene fusions

Detailed Description
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TL118 is an orally active inhibitor of the tropomyosin receptor kinase (Trk) family consists of TrkA, TrkB, and TrkC. These receptors are encoded by the NTRK1, NTRK2 and NTRK3 genes, and oncogenic fusions of NTRK may cause cancer cells to grow and spread in the body. The purpose of this study is to explore how effective TL118 is for the treatment of patients with solid tumors harboring NTRK gene fusions.

Official Title
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A Phase 2 Study of TL118 for the Treatment of Patients With Solid Tumors Harboring NTRK Gene Fusions

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: TL118 Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years old and above, male or female Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumor that harbors an NTRK1/2/3 gene fusion that is predicted to translate into a fusion protein with a functional tropomyosin receptor kinase (TRK)A/B/C kinase domain, without a concomitant second onco-driver 3) Patients must have had disease progression during or after prior treatment for their tumor, or would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy or are not suitable - in the opinion of the Investigator - to receive standard of care therapy; prior treatment with approved or investigational TRK inhibitors in patients who have tumors that harbor NTRK1/2/3 gene rearrangements is not allowed, except for prior TRK treatment for less than 28 days due to intolerable toxicity) At least one measurable lesion Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 A minimum life expectancy of > 3 months Adequate bone marrow reserve, hepatic, renal, and coagulation function Other inclusion criteria apply for participating in the Study Exclusion Criteria: Any systemic anti-tumor therapy such as chemotherapy and radiation therapy (including curative radiotherapy or spinal radiotherapy portion > 30%) used within 3 weeks prior to enrollment; immunotherapy within 4 weeks; any palliative radiotherapy for non-target lesions used to relieve symptoms and traditional Chinese medicines (TCMs) indicated for the tumor (including Chinese patent medicine) within 2 weeks prior to enrollment Participation in another interventional clinical trial 2 weeks prior to enrollment or within 5 half-lives from the last dose of IP (whichever is shorter) Any unresolved toxicities from prior therapy greater than Grade 1, at the time of screening with the exception of toxicities posing no safety risk in the opinion of the Investigator Active central nervous system metastases Any other primary malignant tumors within 3 years (except for cured skin basal cell carcinoma and carcinoma in situ of cervix, low-risk cancer Any active infection which has not been controlled at screening Other exclusion criteria apply for participating in the Study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm, Open label<br>Participants will receive TL118 capsule taken orally with (preferred) or without food, 252 mg twice daily, 28 days for a cycle. | Drug: TL118 Capsule<br>* Oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) |  | Pre-dose up to approximately 24 months post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DoR) |  | Pre-dose up to approximately 24 months post-dose | 
| Disease Control Rate (DCR) |  | Pre-dose up to approximately 24 months post-dose | 
| Progression Free Survival (PFS) |  | Pre-dose up to approximately 24 months post-dose | 
| Time to Tumor Progression (TTP) |  | Pre-dose up to approximately 24 months post-dose | 
| Time to Response (TTR) |  | Pre-dose up to approximately 24 months post-dose | 
| Time to Treatment Failure (TTF) |  | Pre-dose up to approximately 24 months post-dose | 
| Overall Survival (OS) |  | Pre-dose up to approximately 24 months post-dose | 
| 1-year Progression Free Survival |  | Pre-dose up to approximately 24 months post-dose | 
| 1-year Survival |  | Pre-dose up to approximately 24 months post-dose | 
| Number of Participants Experiencing Adverse Events (AE) |  | Pre-dose up to approximately 24 months post-dose | 
| Number of Participants Experiencing Adverse Drug Reactions (ADR) |  | Pre-dose up to approximately 24 months post-dose | 
| Number of Participants Experiencing Serious Adverse Events (SAE) |  | Pre-dose up to approximately 24 months post-dose | 
| Number of Participants Experiencing Serious Adverse Reactions (SAR) |  | Pre-dose up to approximately 24 months post-dose | 
| Area Under The Curve (AUC) of TL118 |  | Pre-dose up to 12 hours post-dose | 
| Maximum Plasma Concentration (Cmax) of TL118 |  | Pre-dose up to 12 hours post-dose | 
| Minimum Plasma Concentration (Cmin) of TL118 |  | Pre-dose up to 12 hours post-dose | 
| Time to Peak Drug Concentration (Tmax) of TL118 |  | Pre-dose up to 12 hours post-dose | 
| TL118 half-life (T1/2) |  | Pre-dose up to 12 hours post-dose | 
| Apparent Clearance (CL/f) of TL118 |  | Pre-dose up to 12 hours post-dose | 
| Volume of Distribution (Vz/F) of TL118 |  | Pre-dose up to 12 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oncology, TL118, Teligene, Cancer