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

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ClinicalTrials.gov Identifier: NCT04395677
Recruitment Status : Recruiting
First Posted : May 20, 2020
Last Update Posted : February 3, 2021
Sponsor:
Information provided by (Responsible Party):
AnHeart Therapeutics Inc.

Tracking Information
First Submitted Date  ICMJE May 12, 2020
First Posted Date  ICMJE May 20, 2020
Last Update Posted Date February 3, 2021
Actual Study Start Date  ICMJE July 7, 2020
Estimated Primary Completion Date December 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 19, 2020)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2020)
  • 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
  • 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
  • Maximum Plasma Concentration [Cmax] [ Time Frame: Day 1 to Cycle1Day15 ]
    The Cmax of Cycle1Day1 and Cycle1Day15 will be assessed, (each cycle is 21 days)
  • 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)
  • 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)
  • Trough plasma concentration [Ctrough] [ Time Frame: Day 1 to Cycle1Day15 ]
    The Cthrough of Cycle1Day1 and Cycle1Day15 will be assessed, (each cycle is 21 days)
  • 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)
  • 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
  • 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
  • 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.
  • 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
  • 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
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of AB-106 in Subjects With Advanced NSCLC Harboring ROS1 Fusion Gene
Official Title  ICMJE A Multicenter, Open Label, Single Arm Phase 2 Study of AB-106 in the Treatment of Locally Advanced and Metastatic NSCLC
Brief Summary The purpose of the study is to evaluate safety, pharmacokinetics and efficacy of AB-106 monotherapy in the treatment of advanced NSCLC.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non Small Cell Lung Cancer
Intervention  ICMJE Drug: AB-106

Stage 1: 400mg QD for 3 patients and 600mg QD for 3 patients

Stage 2: 600mg QD

Other Name: DS-6051b
Study Arms  ICMJE Experimental: AB-106 (DS-6051b)
Single-arm trial whereby all consented, enrolled, eligible patients receive AB-106
Intervention: Drug: AB-106
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 19, 2020)
106
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2025
Estimated Primary Completion Date December 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AnHeart Clinical Development +86 21 64746017 AB-106-C203@anhearttherapeutics.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04395677
Other Study ID Numbers  ICMJE AB-106-C203
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party AnHeart Therapeutics Inc.
Study Sponsor  ICMJE AnHeart Therapeutics Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Oncology Shanghai Pulmonary Hospital, Shanghai, China
PRS Account AnHeart Therapeutics Inc.
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP