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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: AB-106

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shuangmiao Wang; Phone Number: 08610-65211007; Email: smwang@anhearttherapeutics.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Chinese PLA General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single-arm trial whereby all consented, enrolled, eligible patients receive AB-106	Drug: AB-106; 600mg QD for each subjects.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AnHeart Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2021
• Primary Completion (ANTICIPATED): April 30, 2024
• Study Completion (ANTICIPATED): December 31, 2026

Study Registration Dates

• First Submitted: October 30, 2020
• First Submitted That Met QC Criteria: October 30, 2020
• First Posted (ACTUAL): November 5, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 21, 2021
• Last Update Submitted That Met QC Criteria: June 18, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: AB-106-C205

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No