A Study of AB-106 in Subjects With Advanced NSCLC Harboring ROS1 Fusion Gene

• ClinicalTrials.gov Identifier: NCT04395677
• Recruitment Status: Recruiting
• First Posted: May 20, 2020
• Last Update Posted: June 18, 2021
• Sponsor: AnHeart Therapeutics Inc.
• Information provided by (Responsible Party): AnHeart Therapeutics Inc.

Study Description

Brief Summary:

The purpose of the study is to evaluate safety, pharmacokinetics and efficacy of AB-106 monotherapy in the treatment of advanced NSCLC.

Condition or disease	Intervention/treatment	Phase
Non Small Cell Lung Cancer	Drug: AB-106	Phase 2

Detailed Description:

This is a Phase 2, multicenter, single-arm, open label study of AB-106 in the Chinese patients of NSCLC harboring with ROS1 fusion gene.

The study will consist of 2 parts. The Part 1 portion will evaluate the safety and PK profile of AB-106 by using two doses of 400mg QD and 600mg QD in order to confirm 600mg QD as the most optimal dose.

The Part 2 portion will evaluate the efficacy and safety of AB-106 by using the most optimal dose of 600mg QD.

It is expected to enroll 6 patients in Part 1 and 100 patients in Part 2. The study period of each patient will be comprised of screening, treatment, safety follow-up and survival follow-up.

In the Part 1 portion, 3 patients will receive AB-106 400mg QD and 3 patients will receive AB-106 600mg QD in 21-cycles to evaluate the safety and PK profiles.

In the Part 2 portion, 100 patients will be enrolled and divided into 2 cohorts. 60 crizotinib-naïve patients will be enrolled in Cohort A and 40 crizotinib-pretreated patients will be enrolled in Cohort B.

AB-106 will be administered 600mg once daily in 21-day cycles. Patients will continue with the study treatment until progression of disease as determined by the investigator.

The tumor response evaluation will be conducted in every two cycles in the first 8 cycles, and then every four cycles until progression of disease as determined by the investigator. The long-term survival follow up will be conducted every 12 weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 106 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open Label, Single Arm Phase 2 Study of AB-106 in the Treatment of Locally Advanced and Metastatic NSCLC
• Actual Study Start Date: July 7, 2020
• Estimated Primary Completion Date: December 30, 2023
• Estimated Study Completion Date: December 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: AB-106 （DS-6051b）; Single-arm trial whereby all consented, enrolled, eligible patients receive AB-106	Drug: AB-106; Stage 1: 400mg QD for 3 patients and 600mg QD for 3 patients Stage 2: 600mg QD; Other Name: DS-6051b

Outcome Measures

Primary Outcome Measures :

1. Best overall response (BOR) by IRC [ Time Frame: 6 months ]
   Best overall response (BOR) based on independent radiology review by Independent Review Committee(IRC) according to RECIST 1.1

Secondary Outcome Measures :

1. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: 25 months ]
   Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
2. Rate of ECG QT Interval prolongation patients in all patients [ Time Frame: 25 months ]
   After the medicine, the number of patients with ECG QT Interval and the rate of patients with clinical significant
3. Maximum Plasma Concentration [Cmax] [ Time Frame: Day 1 to Cycle1Day15 ]
   The Cmax of Cycle1Day1 and Cycle1Day15 will be assessed, (each cycle is 21 days)
4. Area under the curve from time zero to τ (dose interval τ is 24 h in this study) [AUCτ] [ Time Frame: Day 1 to Cycle1Day15 ]
   The AUCτ of Cycle1Day1 and Cycle1Day15 will be assessed, (each cycle is 21 days)
5. Average plasma concentration at steady state over dosing interval [Cav] [ Time Frame: Day 1 to Cycle1Day15 ]
   The Cav of Cycle1Day1 and Cycle1Day15 will be assessed, (each cycle is 21 days)
6. Trough plasma concentration [Ctrough] [ Time Frame: Day 1 to Cycle1Day15 ]
   The Cthrough of Cycle1Day1 and Cycle1Day15 will be assessed, (each cycle is 21 days)
7. Time to reach maximum plasma concentration [Tmax] [ Time Frame: Day 1 to Cycle1Day15 ]
   The Tmax of Cycle1Day1 and Cycle1Day15 will be assessed, (each cycle is 21 days)
8. Duration of Response(DOR) [ Time Frame: 25 months ]
   Duration of Response(DOR) based on independent radiology review by Independent Review Committee(IRC) and investigator according to RECIST 1.1
9. Time to Response(TTR) [ Time Frame: 6 months ]
   Time to Response(TTR) based on independent radiology review by Independent Review Committee(IRC) and investigator according to RECIST 1.1
10. Time to Progress(TTP) [ Time Frame: 25 months ]

    Time to Progress(TTP) based on independent radiology review by Independent Review Committee(IRC) and investigator according to RECIST 1.1

    OS defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive.

11. Progression free Survival(PFS) [ Time Frame: 25 months ]
    Progression free Survival(PFS) based on independent radiology review by Independent Review Committee(IRC) and investigator according to RECIST 1.1
12. Intracranial best overall response (IBOR) [ Time Frame: 25 months ]
    Intracranial Best overall response (BOR) based on independent radiology review by Independent Review Committee(IRC) and Investigator according to RANO for intracranial lesion
13. Duration of intracranial response (IDOR) [ Time Frame: 25 months ]
    Duration of intracranial response (IDOR) based on independent radiology review by Independent Review Committee(IRC) and Investigator according to RANO for intracranial lesion
14. Overall Survival(OS) [ Time Frame: 51 months ]
    OS defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Patients must meet all of the following criteria to be eligible for enrollment into the study:

1. ≥ 18 years of age
2. Histologically or cytologically confirmed locally advanced or metastatic NSCLC
3. Positivity of ROS1 fusion is determined by the local qualified laboratories by using the FISH, RT-PCR or NGS assay, and the subject must provide archival tumor tissue sample for the confirmation by a sponsor-designated central laboratory
4. The subject is either TKI treatment naïve(Cohort A)，or has disease progression following the treatment of crizotinib （Cohort B）
5. The patient with brain metastases is either asymptomatic, or neurologically stable for at least 2 weeks prior to study entry
6. Prior therapies (including chemotherapies [less than 3 lines of regimen], radiotherapy [except for palliative], or surgery) should be completed at least 2 weeks prior to study entry. The palliative radiotherapy (≤10 times) should be completed within 48 hours prior to study entry. Any acute toxic effect must be resolved to CTCAE Grade ≤1 except for alopecia
7. At least one measurable target tumor lesion (as accessed by RECIST v1.1) that has not been irradiated
8. ECOG Performance Status: 0 or 1
9. Patient with a life expectancy ≥ 3 months based on the judgement of investigators

10. Adequate organ functions defined by the following criteria：

    • Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤2.5 x ULN; or ≤5 x ULN，if there is liver metastases involvement；
    • Total serum bilirubin ≤1.5 x ULN；
    • Absolute neutrophil count（ANC） ≥1500/µL；
    • Platelet count≥100,000/µL；
    • Hemoglobin≥8.0 g/dL；
    • Serum creatinine ≥2 x ULN.
11. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of the pertinent aspect of the study
12. Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures
13. Male and female patients of childbearing potential must agree to sue effective methods of contraception throughout the study and for 90 days after the last dose of study medication.

Exclusion Criteria:

Patient presenting with any of the following criteria will not be included in the study：

1. Current participation in other therapeutic investigational studies
2. Previous participation in the treatment or clinical trials of other ROS1-TKIs (except for crizotinib)
3. Previous participation in the treatment and clinical trials of ALK or NTRK fusion gene targeted therapies and ICI（PD-1/PD-L1） therapies
4. Spinal cord compression unless the patient demonstrates good pain control and stabilization or recovery of neurological function, carcinomatous meningitis or leptomeningeal disease
5. Patients with interstitial fibrosis or interstitial lung disease
6. Any one of the following currently or in the previous 3 months: myocardial infarction, severe/unstable angina, coronary/ peripheral artery bypass graft, congestive heart failure or cerebrovascular accident including transient ischemic attack
7. Ongoing cardiac dysrhythmias of NCI CTCAE (v5.0) Grade≥2, uncontrolled atrial fibrillation of any grade, or QTc interval>470 microsec
8. Pregnancy or breastfeeding
9. Current use of food or drugs that are known 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. Current use of drugs that are known strong CYP3A4 inducers, including (but not limited to) carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St John's Wort
11. Current use of drugs that are known CYP3A4 substrates with narrow therapeutic indices, including (but not limited to) dihydroergotamine, ergotamine, pimozide, astemizole, cisapride, and terfenadine.
12. Current use of drugs that are known to induce QTc prolongation
13. Systematic treatment with anti-cancer therapy, including any Traditional Chinese Medicine (TCM)with anti-tumor effect indicated in the prescription information.
14. Evidence of active malignancy (other than current NSCLC, non-melanoma skin cancer, in situ cervical cancer, and presumed cured prostate cancer) within the last 3 years
15. Clinically active viral disease with positivity of serum HIV, HBV, HCV, RPR testing
16. Difficult to swallow which may significantly impact drug absorption
17. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation in the judgement of investigator and sponsor

Contacts and Locations

Contacts

Contact: AnHeart Clinical Development; +86 10 65211007; smwang@anhearttherapeutics.com

Locations

China, Shanghai

Shanghai Pulmonary Hospital; Recruiting

Shanghai, Shanghai, China, 200000

Sponsors and Collaborators

AnHeart Therapeutics Inc.

Investigators

• Study Director: Oncology; Shanghai Pulmonary Hospital, Shanghai, China

More Information

• Responsible Party: AnHeart Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT04395677
• Other Study ID Numbers: AB-106-C203
• First Posted: May 20, 2020
• Last Update Posted: June 18, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases