Clinical Trials /

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

NCT04052971

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Carcinoma
  • Melanoma
  • Prostate Carcinoma
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: ABN401-001
  • NCT ID: NCT04052971

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
ABN401- Escalation PhaseEscalation phase
ABN401- Expansion PhaseExpansion phase

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Escalation phaseExperimentalDrug: 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.
  • ABN401- Escalation Phase
Expansion phaseExperimentalDrug: 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.
  • ABN401- Expansion Phase

Eligibility Criteria

        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).
      
Maximum Eligible Age:60 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To evaluate the safety and tolerability of ABN401.
Time Frame:Measurements at Baseline till the last day of Visit
Safety Issue:
Description:Safety and tolerability determined by abnormal clinical laboratory tests, vitals signs, physical exam, ECG parameters, Liver function tests

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description: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)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Abion Inc

Last Updated

January 29, 2020