The goal of this clinical trial is to learn about the safety of drug CG001419. It also learn if drug CG001419 works to treat in locally advanced/metastatic adult solid tumours with NTRK gene fusions, NTRK gene point mutations, and NTRK gene amplification or over expression.
The main questions it aims to answer are:
Phase1:To determind the Maximum Tolerated Dose (MTD) and/or Phase 2 Recommended Dose for Phase 2 (RP2D) of CG001419 administered orally to adult subjects with locally advanced/metastatic solid tumours. To establish the safety and tolerability profile of CG001419.
Phase2:To evaluate the efficacy of CG001419 in adult subjects with locally advanced or metastatic solid tumours harbouring oncogenic NTRK fusions, mutations, amplifications or over expression.
Participants will Receive treatment with CG001419 until disease progression.
Age ≥18 when signing the informed consent form, regardless of gender.
The estimated survival time is ≥3 months.
Histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumors that have failed, are intolerant to, or have no available standard therapy.
Dose Escalation Phase: While testing for NTRK/TRK status is not mandatory, enrollment priority will be accorded to patients whose tumors harbor oncogenic NTRK/TRK alterations. Dose Expansion and Indication Expansion Phases: Enrollment eligibility is contingent upon the confirmation of oncogenic NTRK/TRK alterations, as ascertained through tumor tissue or peripheral blood testing.
None
Single group
CG001419 tablets
DrugFor QD administration, a single dose was given each morning. For BID administration, two doses were given 12 hours apart, one in the morning and one in the evening. Treatment Schedule:Repeated dosing was administered in 28-day treatment cycles.
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Treatment groupsSee each treatment group below.
Phase 1: Maximum Tolerated Dose (MTD)
Defined as the highest dose level at which no more than 1/6 of the subjects experience dose-limiting toxicity(DLT) during the DLT assessment period.
Phase 1: Recommended Phase 2 Dose (RP2D)
Defined as the optimal Phase II dosing regimen explored and selected based on the comprehensive evaluation of the drug's safety, tolerability, pharmacokinetic profile, and efficacy.
Phase1: Incidence of Adverse Events [Safety and Tolerability]
According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, evaluate the safety and tolerability of CG001419 at different doses in the treatment of advanced solid tumors.
Phase 2: Overall response rate (ORR)
The proportion of subjects whose best overall response is Complete Response(CR) or Partial Response(PR) in the study assessed by Independent Central Review(IRC) according to Response Evaluation Criteria in Solid Tumors(RECIST) v1.1.
Objective Response Rate (ORR)
The proportion of subjects whose best overall response is CR or PR in the study assessed by investigator according to RECIST v1.1.
Disease Control Rate（DCR）
Defined as the proportion of subjects assessed by the Independent Central Review (ICR) and the investigator as having a best overall response of CR, PR, or SD according to RECIST v1.1.
Progression-Free Survival（PFS）
Defined as the time from the first administration of CG001419 to the first occurrence of disease progression or death (whichever occurs first), as assessed by the investigator and the Independent Review Committee (IRC) per RECIST 1.1.
Overall Survival（OS）
Defined as the time from the first administration of CG001419 to the subject's death.
Phase 1: Degradation rate of TRK fusion proteins by CG001419 tablets at different concentrations.
Pharmacodynamic (PD) characteristics: exploring the activity of plasma containing different concentrations of CG001419 tablets in degrading TRK fusion proteins ex vivo (outside the living body).
Phase 1: Primary metabolite types and concentrations of CG001419 tablets
Explore and identify the types and concentrations of the primary metabolites of CG001419 tablets.
Phase 2: Longitudinal evolution profile of tumor molecular markers (via tissue and ctDNA sequencing).
When feasible, the acquired resistance mechanisms and the dynamic changes (temporal evolution) of tumor molecular markers are assessed by comparing changes in tumor molecular profiles within tumor tissues and blood samples (circulating tumor DNA \[ctDNA\]) obtained before treatment, during treatment, and at the time of disease progression.
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