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To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of ABN401 in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer Harboring c-MET Dysregulation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04052971
Recruitment Status : Recruiting
First Posted : August 12, 2019
Last Update Posted : May 5, 2022
Sponsor:
Collaborator:
Novotech (Australia) Pty Limited
Information provided by (Responsible Party):
Abion Inc

Tracking Information
First Submitted Date  ICMJE July 26, 2019
First Posted Date  ICMJE August 12, 2019
Last Update Posted Date May 5, 2022
Actual Study Start Date  ICMJE August 1, 2019
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 2, 2022)
  • To evaluate the safety and tolerability of ABN401. [ Time Frame: Measurements at Baseline till the last day of Visit ]
    Safety and tolerability determined by abnormal clinical laboratory tests, vitals signs, physical exam, ECG parameters, Liver function tests
  • To determine the objective response rate (ORR) to ABN401 according to RECIST 1.1 [ Time Frame: Up to 30 days ]
    Objective response rate (ORR) is defined as the proportion of patients who experience a complete response (CR) or partial response (PR) as measured by RECIST 1.1.
Original Primary Outcome Measures  ICMJE
 (submitted: August 8, 2019)
Number of Participants with Treatment Adverse Events [ Time Frame: Measurements at Baseline till the last day of Visit ]
Number of treatment related adverse events as determined by abnormal clinical laboratory tests, vitals signs, physical exam, ECG parameters, Liver function tests
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 2, 2022)
  • To determine the systemic PK of ABN401. [ Time Frame: Dose Escalation Phase: Cycle 1- Day 1, Day 2, Day 5, Day 8, Day 15; Dose Expansion Phase: Cycle 1, Day -2, Day 1, Day 2, Day 8, Day 15 ]
  • To determine preliminary estimate of ABN401 efficacy in patients with selected malignancies [ Time Frame: Screening and at every 6 weeks from C1D1 independent of cycle length ]
    Efficacy will be assessed by CT/MRI Scans of the chest, abdomen and pelvis (patients with lung, pancreatic and ovarian cancer, and if clinically indicated for patients with other malignancies)
  • Evaluate the duration of response (DoR) to ABN401 according to RECIST 1.1 [ Time Frame: Up to 30 days ]
    Duration of response (DoR) is defined as the time period from documentation of disease response to disease progression.
  • Assess the objective disease control rate (DCR) of ABN401 according to RECIST 1.1 [ Time Frame: Up to 30 days ]
    Disease advanced control rate (DCR) is defined as the proportion of patients who achieve CR, PR, and stable disease (SD) as measured per RECIST 1.1.
  • Determine progression free survival (PFS) according to RECIST 1.1 [ Time Frame: Up to 30 days ]
    Progression-free survival (PFS) is defined as the time from first dose of study drug until disease progression or death.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2019)
  • To determine the systemic PK of ABN401. [ Time Frame: Dose Escalation Phase: Cycle 1- Day 1, Day 2, Day 5, Day 8, Day 15; Dose Expansion Phase: Cycle 1, Day -2, Day 1, Day 2, Day 8, Day 15 ]
    Blood samples obtained prior to dosing and serially post-dose will be processed to obtain plasma.Plasma samples will be stored frozen until assayed for ABN401 concentrations using a validated method. A full plasma PK profile will be obtained analyzed using non-compartmental methods for all patients in the dose-escalation part of the study. For the expansion cohorts, sparser sampling and a population approach may be feasible (depending on emerging clinical data).
  • To evaluate the effect of food on PK profile of ABN401 in expansion cohort. [ Time Frame: Cycle 1, Day -2, Day 1, Day 2, Day 8, Day 15 ]
    Blood samples obtained prior to dosing and serially post-dose will be processed to obtain plasma.Plasma samples will be stored frozen until assayed for ABN401 concentrations using a validated method. For the expansion cohorts, sparser sampling and a population approach may be feasible (depending on emerging clinical data).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of ABN401 in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer Harboring c-MET Dysregulation
Official Title  ICMJE A Phase 1-2 Multicenter, Open-Label, Dose-Escalation Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of ABN401 in Patients With Advanced Solid Tumors and Dose-Expansion in Patients With Non-Small Cell Lung Cancer Harboring c-MET Dysregulation
Brief Summary This is a dose escalation, Phase 1-2 study of ABN401 in patients with advanced solid tumors, refractory metastatic disease, or refractory locally advanced disease not amenable to local therapy.
Detailed Description

First part of the study uses single patient cohorts at the initial dose levels, followed by a classic 3+3 design, with enrollment of 3 patients per cohort and expansion to 6 patients in the event of a dose-limiting toxicity (DLT).

The second part of the study consists of expansion cohorts will enroll Non-Small Cell Lung Cancer Harboring patients with c-MET dysregulation.

Once the MTD and RP2D are selected in Phase 1, Phase 2 expansion cohorts may be initiated.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE
  • Drug: ABN401- Escalation Phase
    Dose administration: Escalation Phase The regular dose levels of ABN401 will range from 50 mg to 1800 mg QD daily for 21 days.
  • Drug: ABN401- Expansion Phase

    Dose administration: Expansion Phase The expansion phase of the study will use the dose and schedule determined to be most appropriate in the dose escalation portion of the study. This may be the MTD and/or the RP2D and will consist of cohorts of NSCLC patients with c-MET dysregulation.

    Patients will receive ABN401 800 mg, administered orally once daily for 21 days until disease progression, unacceptable toxicity, or patient withdrawal.

Study Arms  ICMJE
  • Experimental: Escalation phase

    Drug: ABN401

    Route of Administration: Oral

    The study will follow a single patient cohort approach for the first 3 regular dose levels followed by classic 3+3 design. The starting dose is 50mg QD.

    Intervention: Drug: ABN401- Escalation Phase
  • Experimental: Expansion phase

    Drug: ABN401

    Route of Administration: Oral

    Once the maximum tolerated dose (MTD) or highest escalation cohort has been reached, or notable efficacy has been observed at a given dose level, a decision as to Recommended Phase 2 dose (RP2D) will be determined. Up to 40 patients with Non-Small Cell Lung Cancer Harboring c-MET Dysregulation will be recruited.

    Intervention: Drug: ABN401- Expansion Phase
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: August 8, 2019)
78
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed informed consent before any study-specific screening procedures.
  2. Male or female ≥ 18 years of age or designated age of majority according to regulatory authorities, whichever is higher.
  3. Body weight ≥ 40 kg and ≤ 110 kg.
  4. Eastern Cooperative Oncology Group (ECOG) performance status (PS), 0 or 1.
  5. Diagnosis:

    1. For the Phase 1 dose escalation, must have:

      • Histological or cytological diagnosis of melanoma or any type of carcinoma or sarcoma,
      • Refractory metastatic disease, or refractory locally advanced disease not amenable to local therapy,
      • Metastatic breast or prostate cancer may have bone-only disease.
    2. For the Phase 1 extension (pilot expansion), patients must have NSCLC with c-MET overexpression, MET amplification, or MET exon 14 skipping by local biomarker assessment as defined in study protocol. The number of patients with only c-MET overexpression is limited to 50% of enrolled patients in that dosing cohort including escalation and extension.
    3. For Phase 2, must have histologically or cytologically confirmed NSCLC with suspected MET exon 14 skipping by local biomarker assessment and confirmed MET exon 14 skipping by central biomarker assessment as defined in study protocol.
  6. Progressive disease:

    1. Phase 1: Progressive disease on established standard medical anti-cancer therapy for his/her tumor type or intolerant to such therapy, or in the opinion of the investigator considered ineligible for a particular form of standard therapy on medical grounds.
    2. Phase 2: Progressive disease after standard of care treatments with no greater than 2 prior treatment regimens (neoadjuvant, adjuvant, and maintenance therapies do not qualify as separate treatment regimens).
  7. At least one measurable lesion per response evaluation criteria in solid tumors (RECIST) 1.1, with the exception of bone-only disease (i.e., non-measurable disease per RECIST 1.1) with at least 1 radiological non-target lesion.
  8. If not menopausal or surgically sterile, willing to practice at least one of the following highly effective methods of birth control for at least a (partner's) menstrual cycle before and for 3 months after study drug administration:

    1. True abstinence, when this is in line with the preferred and usual lifestyle of the patient, from sexual intercourse with a member of the opposite sex,
    2. Sexual intercourse with vasectomized male/sterilized female partner,
    3. Hormonal female contraceptive (oral, parenteral, intravaginal, implantable or transdermal) for at least 3 consecutive months prior to investigational product administration (when not clinically contraindicated as in breast, ovarian and endometrial cancers),
    4. Use of an intrauterine contraceptive device.
  9. Resolution of prior-therapy-related AEs (including immune-related AEs but excluding alopecia) to ≤ Grade 1 per CTCAE, and no treatment for these AEs for at least 2 weeks prior to the time of enrollment. Alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 AEs not constituting a safety risk based on investigator's judgment are acceptable.
  10. Phase 1 only: minimum of 2 weeks since last dose of hormone therapy.
  11. Minimum of > 2 weeks or > 5 half-lives (whichever is longer) between the start of study treatment since last dose of radiotherapy, chemotherapy, or molecularly targeted agents or tyrosine kinase inhibitors; minimum of > 3 weeks of the start of study treatment since last dose of immunotherapy/monoclonal antibodies; > 6 weeks of the start of study treatment since the last dose of nitrosoureas, antibody-drug conjugates or radioactive isotopes.
  12. Adequate organ function as indicated by the laboratory values.
  13. Tissue and/or blood specimens:

    1. Phase 1: Available archival formalin-fixed, paraffin-embedded tumor tissue specimen.

      The archival tissue must be:

      • collected after progression from most recent prior systemic anti-cancer treatment, OR
      • the samples of previous lines of treatment. If patient wants to participate to the study but does not want to give the blood and tissue samples for the exploratory study, patient might be able to participate after discussion and approval of sponsor and the medical monitor.
    2. Phase 2: Biomarker Criteria: Willing to undergo a new biopsy or have available archival formalin-fixed, paraffin-embedded tumor tissue specimen. The archival tissue must be:

      • collected after progression from most recent prior systemic anti-cancer treatment, OR
      • tissue samples collected prior to previous lines of treatment, OR, if biopsy is not possible and archival tissue is unavailable:
      • Must undergo blood sample for biomarker assessment
  14. If the patient agrees to optional pre- and/or study new tumor biopsies (that can be biopsied based on investigator's assessment) and to provide the tissue for biomarker analysis, a signed informed consent for the biopsy is required. Tissue obtained for the biopsy must not be previously irradiated. No systemic antineoplastic therapy may be received by the patient between the time of the biopsy and the first administration of ABN401.

    For escalation, each dose escalation cohort must try to enroll at least 1 patient who agrees to biopsies. An exception to the requirement for a new tumor biopsy in at least one patient per dose level is that if the first patient in a single dose cohort does not consent to a new tumor biopsy and the cohort is not expanded to 3 or 6 patients, a biopsy will not be required in that cohort. Note: During pre-treatment FFPE tissue samples (unstained slides or blocks) or new frozen tissue may be provided for tumor analyses.

  15. Able and willing to comply with the protocol and the restrictions and assessments therein.

Exclusion Criteria:

  1. Previous severe hypersensitivity reaction to any component of ABN401.
  2. Prior therapy:

    1. Phase 1: Treatment with more than 4 lines of prior systemic therapy for recurrent/metastatic disease. If the patient was treated with more than 4 lines but his/her condition is eligible to participate to the trial by the investigator's judgement, the patient might be able to be enrolled to the trial under the medical monitor and the sponsor's approval,
    2. Phase 2: Previous treatment with c-MET inhibitors or HGF-targeting therapy.
  3. Genetic analysis:

    1. Phase 1 Extension Cohort, existing data by genetic analysis of the patient's tumor tissue that may result in an increased probability of being resistant to c-MET inhibitors, including 1) EGFRi; 2) ALKi; 3) ROSi; 4) BRAFi; 5) NTRKi; 6) RETi,
    2. Phase 2 Expansion Cohorts: existing genetic data from the patient's tumor tissue showing known molecular alterations which would make them eligible for targeted therapies (such as EGFR mutations, ALK rearrangements, KRAS mutation, ROS1 translocation, BRAF mutation, RET alteration, and NTRK fusion, etc.).
  4. Chronic inflammatory liver condition. History or clinical evidence of any liver or biliary pathology including cirrhosis, infectious disease, inflammatory conditions, steatosis, or cholangitis (including ascending cholangitis, primary sclerosing cholangitis, obstruction, perforation, fistula of biliary tract, spasm of sphincter of Oddi, biliary cyst or biliary atresia).
  5. Prior organ or stem cell transplant.
  6. Known active infection with HIV, HTLV-1, hepatitis B virus (HBV), or hepatitis C virus (HCV):

    1. Patients with a history of hepatitis B or C are allowed if HBV DNA or HCV RNA are undetectable,
    2. Active infection with human immunodeficiency virus (HIV) and CD4+ T-cell count <350/μL. Patients not on established ART for at least four weeks and having a detectable HIV viral load.
  7. Symptomatic ascites or pleural effusion, unless clinically stable for at least two weeks following treatment for these conditions (including therapeutic thoraco- or paracentesis).
  8. Known active CNS primary tumor or metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to first dose of study drug, have no evidence of new or enlarging brain metastases and are off steroids for at least 15 days prior to first dose of study drug.
  9. Known history of a hematologic malignancy, malignant primary brain tumor, or of a second malignant primary solid tumor (other than that under study), unless the patient has undergone potentially curative therapy with no evidence of that disease for 3 years. Note: The time requirement for no evidence of disease for 3 years does not apply to patients who underwent successful definitive resection of non-melanoma skin cancer, superficial bladder cancer, in situ cervical cancer, or other in situ cancers.
  10. Active infection requiring therapy. However, subject with minor infections where oral antibiotic required, (e.g., urinary tract infection, Upper respiratory tract infection, etc.) could be eligible based on investigator's judgement.
  11. Use of systemic corticosteroids > 10 mg/day prednisone or equivalent within 30 days or other immunosuppressive drugs within 30 days prior to first drug administration.
  12. Received an investigational product or been treated with an investigational device within 30 days prior to first drug administration.
  13. Has been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents or tyrosine kinase inhibitors within 2 weeks or 5 half-lives (whichever is longer) of the start of study treatment; immunotherapy/monoclonal antibodies within 3 weeks of the start of study treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of study treatment; 7-day washout is permitted for palliative radiation (i.e. limited field, ≤ 14-day course of radiotherapy) to non-CNS lesions.
  14. History or clinical evidence of any surgical or medical condition which the investigator judges as likely to interfere with the results of the study or pose an additional risk in participating e.g., rapidly progressive or uncontrolled disease involving a major organ system-vascular, cardiac, pulmonary, gastrointestinal, gynecologic, hematologic, neurologic, neoplastic, renal, endocrine, autoimmune or an immunodeficiency, or clinically significant active psychiatric or abuse disorders.
  15. Is a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
  16. Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.
  17. Patients with a corrected QT interval (using Fridericia's correction formula) (QTcF) of >470 msec (females) and >450 msec (males).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sangsuk Lee +82-2-6006-4767 sangsuk.lee@abionbion.com
Contact: Jeesun Kim +82-2-6022-6428 jeesun.kim@abionbio.com
Listed Location Countries  ICMJE Australia,   Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04052971
Other Study ID Numbers  ICMJE ABN401-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Abion Inc
Study Sponsor  ICMJE Abion Inc
Collaborators  ICMJE Novotech (Australia) Pty Limited
Investigators  ICMJE Not Provided
PRS Account Abion Inc
Verification Date May 2022

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