Basket Study of AB-106 for the Treatment of Patients With Solid Tumors With NTRK Fusion Gene
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Single-arm trial whereby all consented, enrolled, eligible patients receive AB-106
|
Drug: AB-106
600mg QD for each subjects.
|
Outcome Measures
Primary Outcome Measures
- Best overall response (BOR) [Approximately 24 months]
Assessed by Independent Review Committee (IRC) using RECIST v1.1
Secondary Outcome Measures
- Best overall response (BOR) [Approximately 24 months]
Assessed by Investigator using RECIST v1.1Investigator.
- Duration of response (DOR) [Approximately 24 months]
Assessed by Independent Review Committee (IRC) and Investigator using RECIST v1.1
- Time to Response (TTR) [Approximately 24 months]
Assessed by Independent Review Committee (IRC) and Investigator using RECIST v1.1
- Time to Progress (TTP) [Approximately 24 months]
Assessed by Independent Review Committee (IRC) and Investigator using RECIST v1.1
- Intracranial best overall response (IBOR) [Approximately 24 months]
Assessed by Independent Review Committee (IRC) and Investigator using RANO for subjects with intracranial metastasis at baseline.
- Intracranial Duration of intracranial response (IDOR) [Approximately 24 months]
Assessed by Independent Review Committee (IRC) and Investigator using RANO for subjects with intracranial metastasis at baseline.
- Progression free Survival (PFS) [Approximately 30 months]
Assessed by Independent Review Committee (IRC) and Investigator using RECIST v1.1
- Overall survival (OS) [Approximately 36 months]
Assessed by Kaplan-Meier method
- Adverse events (AE) [Approximately 36 months]
Type, incidence, severity, timing, seriousness, and relatedness of adverse events and laboratory abnormalities, graded by the NCI CTCAE 5.0
- Plasma drug concentration (PK) [Approximately 60 days]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of locally advanced or systemic metastatic solid tumors with NTRK1/2/3 fusion gene;
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Subjects who failed or refused to accept the standard treatment;
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At least one measurable target tumor lesion as accessed by RECIST v1.1;
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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.
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Minimum life expectancy of 3 months;
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Adequate organ function defined per protocol;
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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);
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For patients enrolled via local molecular testing, an archival or fresh tumor tissue is required to be submitted for independent central molecular testing;
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Any toxic effect caused by prior therapies must be recovered to CTCAE Grade ≤1 except for alopecia.
Exclusion Criteria:
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Current participation in another therapeutic clinical trial within 4 weeks before first dose;
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Prior treatment with NTRK fusion gene and immune checkpoint inhibitors (including PD-1/PD-L1, etc.);
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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;
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Had major surgery or radiotherapy within one month before the first dose, or were expected to need a major surgery during study;
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Pneumonia caused by interstitial lung disease, interstitial fibrosis, or tyrosine kinase inhibitors;
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Active and uncontrollable systemic bacterial, viral or fungal infectionsx;
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Clinically active viral disease with positivity of serum HIV, HBV, HCV testing;
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Historical immunodeficiency, including acquired, congenital immunodeficiency diseases, or a historical organ transplant;
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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;
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The systematically use of strong CYP3A inducers, including ( but not limited to) carbamazepine, phenobarbital, phenytoin, rifampicin, rifampicin and St. John's grass;
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Any other anti-tumor drug use within 14 days before first dose or during the study;
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Historical, neurological or mental disorders, such as epilepsy or dementia;
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Historical drug abuse;
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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;
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Active gastrointestinal or other malabsorption disease, such as gastrectomy or enterectomy;
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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;
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Cerebrovascular accidents (exclude transient ischemic attacks) occurred within 3 months before first dose;
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Other malignant tumors, exclude cured non-melanoma skin cancer, cervical cancer in situ and prostatic intraepithelial neoplasia;
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Other protocol specified criteria accessed by investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Chinese PLA General Hospital | Beijing | China |
Sponsors and Collaborators
- AnHeart Therapeutics Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AB-106-C205