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

Official title

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

Overview

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

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.

Interventions

• Drug TL118 Capsule
  Oral administration

Primary outcome measures

• Objective Response Rate (ORR) [Time frame: Pre-dose up to approximately 24 months post-dose]

Secondary outcome measures (12)

• Duration of Response (DoR) [Time frame: Pre-dose up to approximately 24 months post-dose]
• Disease Control Rate (DCR) [Time frame: Pre-dose up to approximately 24 months post-dose]
• Progression Free Survival (PFS) [Time frame: Pre-dose up to approximately 24 months post-dose]
• Time to Tumor Progression (TTP) [Time frame: Pre-dose up to approximately 24 months post-dose]
• Time to Response (TTR) [Time frame: Pre-dose up to approximately 24 months post-dose]
• Time to Treatment Failure (TTF) [Time frame: Pre-dose up to approximately 24 months post-dose]
• Overall Survival (OS) [Time frame: Pre-dose up to approximately 24 months post-dose]
• 1-year Progression Free Survival [Time frame: Pre-dose up to approximately 24 months post-dose]
• 1-year Survival [Time frame: Pre-dose up to approximately 24 months post-dose]
• Number of Participants Experiencing Adverse Events (AE) [Time frame: Pre-dose up to approximately 24 months post-dose]
• Number of Participants Experiencing Adverse Drug Reactions (ADR) [Time frame: Pre-dose up to approximately 24 months post-dose]
• Number of Participants Experiencing Serious Adverse Events (SAE) [Time frame: Pre-dose up to approximately 24 months post-dose]

Eligibility criteria

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
• 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 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 16 centers

• Beijing Cancer Hospital — Beijing
• Peking University School and Hospital of Stomatology — Beijing
• Chongqing University Cancer Hospital — Chongqing
• Fujian Cancer Hospital — Fuzhou
• Affiliated Cancer Hospital and Institute of Guangzhou Medical University — Guangzhou
• Harbin medical university cancer hospital — Harbin
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou
• Union Hospital Tongji Medical College Huazhong University of Science and Technology — Wuhan
• … and 8 more centers

United States · 3 centers

• Adventist Health Glendale — Glendale
• Texas Oncology — Dallas
• The University of Texas MD Anderson Cancer Center — Houston

Identifiers

NCT: NCT06010342 · TL-TRK-202101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗