basket study of ab-106 for the treatment of patients with solid tumors with ntrk fusion gene

Conditions: Solid Tumor

Summary: ab-106 will be administered once a day. each treatment cycle is defined as 21 days of continuous medication. dosing will continue until any of the following conditions are met: disease progression, intolerable drug-related adverse events, researchers recommend discontinuation of treatment, withdrawal of informed consent, pregnancy during the study, use of other anti-tumor therapy, loss of follow-up, death and other causes, whichever occurs first. the study includes a screening period, treatment period, safety follow-up and long-term follow-up.


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.