Treatment of solid tumors with NTRK fusion gene using AB-106

A Phase II, Multicenter, Open, Basket Study of AB-106 to Treat the Subjects With Local Progression or Systemic Metastasis Solid Tumors With NTRK Gene Fusion

This study is testing a new drug called AB-106 to see if it can help people with advanced solid tumors that have a specific gene change called NTRK fusion.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: AnHeart Therapeutics Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Beijing)
• Trial ID: NCT04617054 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy of AB-106, administered daily for 21-day cycles, in patients with locally advanced or metastatic solid tumors that harbor NTRK fusion genes. Participants will be monitored for disease progression and adverse effects, with treatment continuing until specific criteria are met. The study includes a screening phase, treatment phase, safety follow-up, and long-term follow-up to assess the drug's impact on tumor response.

Who should consider this trial

Good fit: Ideal candidates are individuals diagnosed with advanced solid tumors that have NTRK1/2/3 fusion genes and have either failed or declined standard treatments.

Not a fit: Patients with solid tumors that do not have NTRK fusion genes or those who are currently receiving other anti-tumor therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with solid tumors that have limited treatment alternatives.

How similar studies have performed: Other studies targeting NTRK fusion genes have shown promising results, indicating that this approach is supported by prior evidence.

Eligibility criteria

Inclusion Criteria:

1. Diagnosis of locally advanced or systemic metastatic solid tumors with NTRK1/2/3 fusion gene;
2. Subjects who failed or refused to accept the standard treatment;
3. At least one measurable target tumor lesion as accessed by RECIST v1.1;
4. Subjects diagnosed with primary CNS tumors should meet the following criteria: (1) Received previous treatment, including radiotherapy, chemotherapy, targeted therapy; (2) At least one measurable lesion by two-dimensional measurement (confirmed by MRI and using RANO). At least one measurable lesion in each dimension should be ≥ 1cm and on more than one image; (3) The imaging exam should be completed within 28 days before dosing, and the disease should be in stable;
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
6. Minimum life expectancy of 3 months;
7. Adequate organ function defined per protocol;
8. Coagulation function: international standardized ratio (INR) ≤ 1.5, and partial prothrombin time (PT) or activated partial prothrombin time (APTT) ≤ 1.5 × ULN (Upper limit of normal);
9. For patients enrolled via local molecular testing, an archival or fresh tumor tissue is required to be submitted for independent central molecular testing;
10. Any toxic effect caused by prior therapies must be recovered to CTCAE Grade ≤1 except for alopecia.

Exclusion Criteria:

1. Current participation in another therapeutic clinical trial within 4 weeks before first dose;
2. Prior treatment with NTRK fusion gene and immune checkpoint inhibitors (including PD-1/PD-L1, etc.);
3. Subjects with symptomatic or unstable brain metastasis (asymptomatic brain metastasis subjects can be selected for) and CNS primary tumor, but need to be in stable for at least 7 days, will be enrolled;
4. Had major surgery or radiotherapy within one month before the first dose, or were expected to need a major surgery during study;
5. Pneumonia caused by interstitial lung disease, interstitial fibrosis, or tyrosine kinase inhibitors;
6. Active and uncontrollable systemic bacterial, viral or fungal infectionsx;
7. Clinically active viral disease with positivity of serum HIV, HBV, HCV testing;
8. Historical immunodeficiency, including acquired, congenital immunodeficiency diseases, or a historical organ transplant;
9. The systematically use of strong CYP3A inhibitors, including ( but not limited to) atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, grapefruit or grapefruit juice;
10. The systematically use of strong CYP3A inducers, including ( but not limited to) carbamazepine, phenobarbital, phenytoin, rifampicin, rifampicin and St. John's grass;
11. Any other anti-tumor drug use within 14 days before first dose or during the study;
12. Historical, neurological or mental disorders, such as epilepsy or dementia;
13. Historical drug abuse;
14. Spinal cord compression caused by tumor (unless the subject's pain is completely controlled and neurological function is stable or restored),cancerous meningitis or leptomeningeal disease; have risk of cerebral hernia determined by investigator;
15. Active gastrointestinal or other malabsorption disease, such as gastrectomy or enterectomy;
16. With 3 months before first dose, have unstable cardiovascular disease like as, myocardial infarction, severe / unstable angina pectoris, coronary artery / peripheral artery bypass grafting, congestive heart failure (NCICTCAEv5.0 ≥ 3), arrhythmia (NCICTCAEv5.0 ≥ 2), uncontrollable atrial fibrillation (arbitrary grade) or female QTcF \> 470ms or male QTcF \> 450ms;
17. Cerebrovascular accidents (exclude transient ischemic attacks) occurred within 3 months before first dose;
18. Other malignant tumors, exclude cured non-melanoma skin cancer, cervical cancer in situ and prostatic intraepithelial neoplasia;
19. Other protocol specified criteria accessed by investigator.

Where this trial is running

Beijing

• Chinese PLA General Hospital — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Shuangmiao Wang

Conditions Solid Tumor