Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

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. Identifier: NCT04052971
Recruitment Status : Recruiting
First Posted : August 12, 2019
Last Update Posted : January 30, 2020
Novotech (Australia) Pty Limited
Information provided by (Responsible Party):
Abion Inc

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: ABN401- Escalation Phase Drug: ABN401- Expansion Phase Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 1, 2019
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Safety

Arm Intervention/treatment
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.

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.

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.

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.

Primary Outcome Measures :
  1. 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

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04052971

Layout table for location contacts
Contact: Minseon Lee +82-2-6006-7621
Contact: Jeesun Kim +82-2-6022-6428

Layout table for location information
Australia, New South Wales
ST George Private Hospital Recruiting
Kogarah, New South Wales, Australia, 2217
Contact: Paul De Souza, Dr    +61295539588      
Sydney Southwest Private Hospital Recruiting
Liverpool, New South Wales, Australia, 2170
Contact: Aflah Roohullah, Dr    +61246344366      
Scientia Clinical Research Recruiting
Randwick, New South Wales, Australia, 2031
Contact: Charlotte Lemech, Dr    +61293825807      
Australia, Western Australia
Linear Clinical Research Recruiting
Perth, Western Australia, Australia, 6009
Contact: Michael Millward, Dr    +61861510923      
Korea, Republic of
National Cancer Centre Recruiting
Goyang-si, Gyeonggi-Do, Korea, Republic of, 10408
Contact: Ji-Youn Han, Dr    +82319201154      
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 03080
Contact: Tae Min Kim, Dr    +82220723559      
Yonsei University Health System, Severance Recruiting
Seoul, Korea, Republic of, 03722
Contact: Byoung Chul Cho, Dr    +82222280880      
Asan Medical Centre Recruiting
Seoul, Korea, Republic of, 05505
Contact: Daeho Lee    +82230103214      
Sponsors and Collaborators
Abion Inc
Novotech (Australia) Pty Limited
Additional Information:
Layout table for additonal information
Responsible Party: Abion Inc Identifier: NCT04052971    
Other Study ID Numbers: ABN401-001
First Posted: August 12, 2019    Key Record Dates
Last Update Posted: January 30, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms