Clinical trial NCT04617054: Basket Study of AB-106 for the Treatment of Patients With Solid Tumors With NTRK Fusion Gene
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Solid Tumor
Lead sponsor: AnHeart Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2020-11-05
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Best overall response (BOR)
timeFrame: Approximately 24 months
Secondary outcomes:
measure: Best overall response (BOR)
timeFrame: Approximately 24 months
measure: Duration of response (DOR)
timeFrame: Approximately 24 months
measure: Time to Response (TTR)
timeFrame: Approximately 24 months
measure: Time to Progress (TTP)
timeFrame: Approximately 24 months
measure: Intracranial best overall response (IBOR)
timeFrame: Approximately 24 months
measure: Intracranial Duration of intracranial response (IDOR)
timeFrame: Approximately 24 months
measure: Progression free Survival (PFS)
timeFrame: Approximately 30 months
measure: Overall survival (OS)
timeFrame: Approximately 36 months
measure: Adverse events (AE)
timeFrame: Approximately 36 months
measure: Plasma drug concentration (PK)
timeFrame: Approximately 60 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
Study officials:
References: