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

Phase 2

Recruiting

• Conditions: Solid Tumor
• Interventions: Drug: AB-106

• Registration Number: NCT04617054
• Lead Sponsor: AnHeart Therapeutics Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-10-30
• Study First Submitted QC: 2020-10-30
• Study First Posted: 2020-11-05
• Status Verified: 2021-06
• Study Start: 2021-06-01
• Last Update Submitted: 2021-06-18
• Last Update Posted: 2021-06-21
• Primary Completion: 2024-04-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single-arm trial whereby all consented, enrolled, eligible patients receive AB-106	AB-106	-

Primary Outcome Measures

Name	Time	Method
Best overall response (BOR)	Approximately 24 months	Assessed by Independent Review Committee (IRC) using RECIST v1.1

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Chinese PLA General Hospital; 🇨🇳 Beijing, China