Basket Study of AB-106 for the Treatment of Patients With Solid Tumors With NTRK Fusion Gene

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: AB-106


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of locally advanced or systemic metastatic solid tumors with NTRK1/2/3 fusion gene; Subjects who failed or refused to accept the standard treatment; At least one measurable target tumor lesion as accessed by RECIST v1.1; 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; Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Minimum life expectancy of 3 months; Adequate organ function defined per protocol; 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); For patients enrolled via local molecular testing, an archival or fresh tumor tissue is required to be submitted for independent central molecular testing; Any toxic effect caused by prior therapies must be recovered to CTCAE Grade ≤1 except for alopecia. Exclusion Criteria: Current participation in another therapeutic clinical trial within 4 weeks before first dose; Prior treatment with NTRK fusion gene and immune checkpoint inhibitors (including PD-1/PD-L1, etc.); 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; Had major surgery or radiotherapy within one month before the first dose, or were expected to need a major surgery during study; Pneumonia caused by interstitial lung disease, interstitial fibrosis, or tyrosine kinase inhibitors; Active and uncontrollable systemic bacterial, viral or fungal infectionsx; Clinically active viral disease with positivity of serum HIV, HBV, HCV testing; Historical immunodeficiency, including acquired, congenital immunodeficiency diseases, or a historical organ transplant; 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; The systematically use of strong CYP3A inducers, including ( but not limited to) carbamazepine, phenobarbital, phenytoin, rifampicin, rifampicin and St. John's grass; Any other anti-tumor drug use within 14 days before first dose or during the study; Historical, neurological or mental disorders, such as epilepsy or dementia; Historical drug abuse; 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; Active gastrointestinal or other malabsorption disease, such as gastrectomy or enterectomy; 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; Cerebrovascular accidents (exclude transient ischemic attacks) occurred within 3 months before first dose; Other malignant tumors, exclude cured non-melanoma skin cancer, cervical cancer in situ and prostatic intraepithelial neoplasia; Other protocol specified criteria accessed by investigator.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-arm trial whereby all consented, enrolled, eligible patients receive AB-106<br> | Drug: AB-106<br>* 600mg QD for each subjects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best overall response (BOR) | Assessed by Independent Review Committee (IRC) using RECIST v1.1 | Approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best overall response (BOR) | Assessed by Investigator using RECIST v1.1Investigator. | Approximately 24 months | 
| Duration of response (DOR) | Assessed by Independent Review Committee (IRC) and Investigator using RECIST v1.1 | Approximately 24 months | 
| Time to Response (TTR) | Assessed by Independent Review Committee (IRC) and Investigator using RECIST v1.1 | Approximately 24 months | 
| Time to Progress (TTP) | Assessed by Independent Review Committee (IRC) and Investigator using RECIST v1.1 | Approximately 24 months | 
| Intracranial best overall response (IBOR) | Assessed by Independent Review Committee (IRC) and Investigator using RANO for subjects with intracranial metastasis at baseline. | Approximately 24 months | 
| Intracranial Duration of intracranial response (IDOR) | Assessed by Independent Review Committee (IRC) and Investigator using RANO for subjects with intracranial metastasis at baseline. | Approximately 24 months | 
| Progression free Survival (PFS) | Assessed by Independent Review Committee (IRC) and Investigator using RECIST v1.1 | Approximately 30 months | 
| Overall survival (OS) | Assessed by Kaplan-Meier method | Approximately 36 months | 
| Adverse events (AE) | Type, incidence, severity, timing, seriousness, and relatedness of adverse events and laboratory abnormalities, graded by the NCI CTCAE 5.0 | Approximately 36 months | 
| Plasma drug concentration (PK) |  | Approximately 60 days |