A Phase 1/2 Study of CG001419 Tablets in Adult Subjects With Locally Advanced or Metastatic Solid Tumours Harbouring NTRK Gene Abnormalities

NCT07394374 | Recruiting Phase 1

• 2 other identifiers: CG-NTRK-1419001CTR20222742
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

NTRK; NTRK Gene Fusion; NTRK Fusion Positive; Solid Tumors Harboring NTRK Fusion

Keywords

NRTK; CG001419

Outcome Measures

Primary Outcomes (4)

• 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.

  After the first treatment cycle（each cycle is 28 days）, DLT assessment

• 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.

  Approximately 3 years

• 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.

  Approximately 3 years

• 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.

  The entire test cycle, approximately 8 years.

Secondary Outcomes (14)

• Objective Response Rate (ORR)

  The entire test cycle, approximately 8 years.

• Disease Control Rate（DCR）

  The entire test cycle, approximately 8 years.

• Progression-Free Survival（PFS）

  The entire test cycle, approximately 8 years.

• Overall Survival（OS）

  Up to 10 years after the first administration of the last subject.

• Cmax

  The entire test cycle, approximately 8 years.

Other Outcomes (3)

• Phase 1: Degradation rate of TRK fusion proteins by CG001419 tablets at different concentrations.

  Approximately 3 years

• Phase 1: Primary metabolite types and concentrations of CG001419 tablets

  Approximately 3 years

• Phase 2: Longitudinal evolution profile of tumor molecular markers (via tissue and ctDNA sequencing).

  The entire test cycle, approximately 8 years

Study Arms (7)

200 mg QD

EXPERIMENTAL

CG001419

Drug: CG001419 tablets

200 mg BID

EXPERIMENTAL

CG001419

Drug: CG001419 tablets

400 mg QD

EXPERIMENTAL

CG001419

Drug: CG001419 tablets

800 mg QD

EXPERIMENTAL

CG001419

Drug: CG001419 tablets

600 mg QD

EXPERIMENTAL

CG001419

Drug: CG001419 tablets

1200 mg QD

EXPERIMENTAL

CG001419

Drug: CG001419 tablets

1600 mg QD

EXPERIMENTAL

CG001419

Drug: CG001419 tablets

Interventions

CG001419 tablets DRUG

For 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.

1200 mg QD; 1600 mg QD; 200 mg BID; 200 mg QD; 400 mg QD; 600 mg QD; 800 mg QD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

1. Age ≥18 when signing the informed consent form, regardless of gender. 2. The estimated survival time is ≥3 months. 3. Histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumors that have failed, are intolerant to, or have no available standard therapy. 4. 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. 5. The Indication Expansion Phase will enroll subjects into the following three cohorts, with respective entry criteria: Cohort 1: Subjects with a confirmed oncogenic NTRK fusion who have not received prior treatment with entrectinib, larotrectinib, and/or other selective TRK-TKIs. Cohort 2: Subjects with a confirmed oncogenic NTRK fusion who have experienced treatment failure with entrectinib, larotrectinib, and/or other selective TRK-TKIs. Cohort 3: Subjects with confirmed non-fusion NTRK alterations, including point mutations, gene amplification, or TRK protein overexpression, and a positive pan-TRK immunohistochemistry (IHC) result, regardless of prior TRK-TKI treatment. Notes:1)NTRK point mutations include Single Nucleotide Variants (SNVs) and Insertion-Deletions (InDels). 2)Positive pan-TRK IHC is defined as \>1% of tumor cells staining stronger than the background (with an intensity ≥1+).3) NTRK gene amplification is defined as a DNA copy number ≥4 and a positive pan-TRK IHC result.TRK protein overexpression is defined as ≥2+ pan-TRK IHC staining in \>5% of tumor cells.4) Over-expression of TRK protein is defined as \> 5% tumor cells with pan-TRK protein immunohistochemical staining ≥2+. 6. Must have at least one measurable target lesion according to RECIST v1.1. (For patients with HCC, mRECIST v1.1 should be used; for patients with primary CNS tumors or brain metastases, RANO criteria may be used.). During the Dose-Finding Phase, evaluable but non-measurable lesions are acceptable. 7. Subjects with primary CNS tumors or brain metastases must be clinically stable for at least 2 weeks after prior treatment, with no requirement for corticosteroids, or be on a stable or decreasing dose of ≤4 mg/day of dexamethasone (or equivalent) for at least 4 weeks. Concomitant administration of prophylactic, non-hepatic enzyme-inducing antiepileptic drugs is permitted. 8. The physical fitness status (PS) score of the American Eastern Cancer Cooperative Group (ECOG) is ≤ 2. 9. The subject agrees to provide either the results of genetic testing from a tumor tissue specimen obtained within 1 year after the completion of the prior therapy from a laboratory capable of ensuring quality results, or a tumor tissue specimen (archival or fresh biopsy) and/or peripheral blood for NTRK status confirmation, and is willing to consider undergoing a tumor biopsy and/or providing peripheral blood during the study for the assessment of changes in tumor molecular status, if deemed safe and feasible by the Investigator. 10. Adequate organ function must be confirmed by laboratory test results within 7 days prior to the first dose of study drug, meeting all the following criteria: 1)Absolute Neutrophil Count (ANC) ≥1.5×10⁹/L, platelet count ≥90×10⁹/L, and hemoglobin ≥90 g/L, with no transfusion or colony-stimulating factor therapy administered within 14 days prior to the test; 2)Liver function: albumin ≥28 g/L, total bilirubin (TBIL) ≤1.5 × ULN, AST (or SGOT), ALT (or SGPT), and alkaline phosphatase (ALP) ≤2.5 × ULN; for subjects with known Gilbert's syndrome, TBIL ≤3 × ULN and direct bilirubin ≤1.5 × ULN; in the presence of liver metastases: ALT and AST ≤5 × ULN; in the presence of bone metastases: ALP ≤5 × ULN; 3)Renal function: serum creatinine (Cr) ≤1.5 × ULN or calculated creatinine clearance \>50 mL/min (creatinine clearance should be calculated using the Cockcroft-Gault formula). 11\. All toxicities from prior anticancer therapy must have recovered to ≤ Grade 1 according to the NCI-CTCAE version 5.0, with the exception of alopecia and stable chronic conditions. 12\. Be able to swallow tablets (the tablets should be as complete as possible, and can be ground if necessary, but not excessively ground). 13\. Not pregnant or lactating. * Female subjects of childbearing potential (as defined in Appendix 3) must have a negative serum pregnancy test (for beta-human chorionic gonadotropin \[β-hCG\]) at screening. * A female subject is considered NOT to be of childbearing potential if she meets at least one of the following criteria: natural amenorrhea for ≥ 12 consecutive months with corresponding clinical characteristics (e.g., age, history of vasomotor symptoms); or has undergone bilateral oophorectomy, or hysterectomy. However, subjects with bilateral tubal ligation must undergo a serum pregnancy test. * Male subjects with female partners of childbearing potential and female subjects of childbearing potential must agree to use highly effective contraception or practice abstinence during the treatment period and for 90 days after the last dose of CG001419 tablets (detailed contraceptive guidance refers to Appendix 3). Male subjects must also refrain from donating sperm during the study period and for 90 days after the last dose of CG001419 tablets. 14\. The subject voluntarily participates in this study and signs the informed consent form (ICF), demonstrating understanding of the study's purpose, procedures, nature, significance, potential benefits, and risks, and is willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study instructions or procedures.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Cullgen (Shanghai),Inc: lead

Study Sites (6)

The Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, China

RECRUITING

West China Hospital of Sichuan University

Chengdu, China

RECRUITING

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, China

RECRUITING

The Sir Run Run Shaw Hospital, Affiliated to Zhejiang University School of Medicine

Hangzhou, China

RECRUITING

Zhejiang Provincial Cancer Hospital

Hangzhou, China

RECRUITING

Shanxi Provincial Cancer Hospital

Taiyuan, China

RECRUITING

Study Officials

• Ning Li, MD

  The Cancer Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiangyu Jin, MS

CONTACT

+86 13858065096; xiangyu.jin@cullgen.com

Qiao Yi

CONTACT

qiao.yi@cullgen.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2025
• First Posted: February 6, 2026
• Study Start: June 20, 2023
• Primary Completion (Estimated): August 30, 2030
• Study Completion (Estimated): August 30, 2030
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)