CG001419 tablets for adults with advanced solid tumors that have NTRK gene changes.

A Phase 1/2, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CG001419 Tablets in Adult Patients With Locally Advanced/Metastatic Solid Tumors Harboring NTRK Gene Fusions, Mutations, or Amplification/Over Expression.

This will test whether the oral drug CG001419 is safe and can control advanced or metastatic solid tumors in adults whose cancers have NTRK fusions, mutations, or amplifications.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Cullgen (Shanghai),Inc (Academic / other)
• Drugs / interventions: entrectinib, larotrectinib
• Locations: 6 sites (Beijing and 5 other locations)
• Trial ID: NCT07394374 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, open-label, multicenter trial of oral CG001419 given as monotherapy in adults with unresectable locally advanced or metastatic solid tumors. The study includes a dose-finding phase (dose escalation and expansion) to define the maximum tolerated dose and recommended Phase 2 dose, followed by indication-expansion cohorts that require confirmed oncogenic NTRK alterations. Key evaluations include safety, tolerability, pharmacokinetics, and preliminary antitumor activity, with treatment continued until progression or unacceptable toxicity. Patients must have failed or be unsuitable for standard therapy, and some dose-escalation slots may enroll patients without confirmed NTRK status while expansion cohorts require confirmation.

Who should consider this trial

Good fit: Adults aged 18 or older with unresectable locally advanced or metastatic solid tumors who have failed or are unsuitable for standard therapy and who have confirmed oncogenic NTRK alterations are the intended participants, with dose-escalation allowing some patients without confirmed NTRK status.

Not a fit: Patients whose tumors do not harbor oncogenic NTRK alterations, who have very limited life expectancy, or who cannot tolerate investigational therapy are unlikely to benefit from this treatment.

Why it matters

Potential benefit: If successful, CG001419 could provide a new oral targeted option to control tumors driven by NTRK abnormalities for patients with limited standard treatments.

How similar studies have performed: Other selective TRK inhibitors such as larotrectinib and entrectinib have produced high response rates in NTRK fusion–positive cancers, but CG001419 is a new first‑in‑human agent and its activity in patients is unproven.

Eligibility criteria

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.

Where this trial is running

Beijing and 5 other locations

• 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 contacts

• Principal investigator: Ning Li, MD — The Cancer Hospital, Chinese Academy of Medical Sciences
• Study coordinator: Xiangyu Jin, MS

Conditions Solid Tumors Harboring NTRK Fusion; NTRK; NTRK Gene Fusion; NTRK Fusion Positive; NRTK; CG001419