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To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of ABN401 in Patients With Advanced Solid Tumors

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 : January 30, 2020
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 January 30, 2020
Actual Study Start Date  ICMJE August 1, 2019
Estimated Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 20, 2019)
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
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: August 20, 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 ]
  • 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 ]
  • 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)
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
Official Title  ICMJE A Phase 1-2 Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of ABN401 in Patients With Advanced Solid Tumors
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 with patients with c-Met amplification/mutation of interest.

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 patients representing various c-Met-amplification or mutant tumor types of interest.
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 MTD or highest escalation cohort has been reached, or notable efficacy has been observed at a given dose level, a decision as to RP2D will be determined. Upon the establishment of RP2D, up to 4 expansion cohorts of 10-29 patients will be recruited representing various c-Met amplification or mutant tumor types of interest.

    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 March 31, 2021   (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.
  3. Body weight ≥ 40 kg and ≤ 110 kg.
  4. Eastern Cooperative Oncology Group (ECOG) performance status (PS), 0 or 1
  5. Must have any:

    1. Histological or cytological diagnosis of melanoma or any type of carcinoma or sarcoma.
    2. Refractory metastatic disease, or refractory locally advanced disease not amenable to local therapy.
    3. Metastatic breast or prostate cancer, may have bone-only disease.
  6. Progressive disease (PD) 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.
  7. At least one target 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.
  10. 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. Available archival formalin-fixed, paraffin-embedded tumor tissue specimen. If patient wants to participate in the study but does not want to give the blood and tissue samples for the exploratory study, the patient might be able to participate after discussion and approval of sponsor and the medical monitor.
  14. For at least one patient per dose level: Agree to pre- and on-treatment fresh tumor biopsies (that can be biopsied based on investigator's assessment) and to providing the acquired tissue for biomarker analysis. 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. An exception to the requirement for a fresh 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 fresh tumor biopsy and the cohort is not expanded to 3 or 6 patients, a biopsy will not be required in that cohort. At least one fresh tumor biopsy is required in single dose cohorts that are expanded to 3 patients and in all 3+3 cohorts. Note : During pre-treatment FFPE tissue samples (unstained slides or blocks) or fresh frozen tissue can 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. Treatment with more than 4 lines of prior systemic therapy for recurrent/metastatic disease.
  3. 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).
  4. Prior organ or stem cell transplant.
  5. Symptomatic ascites or pleural effusion. A patient who is clinically stable for at least two weeks following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
  6. Known active central nervous system (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 study entry, 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.
  7. 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.
  8. Active infection requiring therapy.
  9. Use of systemic corticosteroids > 10 mg/day prednisone or equivalent within 30 days or other immunosuppressive drugs within 30 days prior to start of the study.
  10. Received an investigational product or treated with an investigational device within 30 days prior to first drug administration.
  11. 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.
  12. Persisting toxicity related to prior therapy (NCI-CTCAE v5 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 AEs not constituting a safety risk based on investigator's judgment are acceptable.
  13. 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.
  14. 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).
  15. Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.
  16. Positive virology/serology for Human Immunodeficiency Virus (HIV)-1, HIV-2, hepatitis B (surface antigen), and hepatitis C ribonucleic acid (RNA) by polymerase chain reaction (PCR).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Minseon Lee +82-2-6006-7621 minseon.lee@abionbio.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 January 2020

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