Clinical Trials /

Enapotamab Vedotin (HuMax-AXL-ADC) Safety Study in Patients With Solid Tumors

NCT02988817

Description:

The purpose of the trial is to determine the maximum tolerated dose and to establish the safety profile of HuMax-AXL-ADC in a mixed population of patients with specified solid tumors

Related Conditions:
  • Malignant Solid Tumor
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: HuMax-AXL-ADC Safety Study in Patients With Solid Tumors
  • Official Title: First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of Axl-specific Antibody-drug Conjugate (HuMax-AXL-ADC) in Patients With Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: GCT1021-01
  • NCT ID: NCT02988817

Conditions

  • Ovarian Cancer
  • Cervical Cancer
  • Endometrial Cancer
  • NSCLC
  • Thyroid Cancer

Interventions

DrugSynonymsArms

Purpose

The purpose of the trial is to establish the tolerability of HuMax-AXL-ADC in a mixed population of patients with specified solid tumors

Detailed Description

The trial consists of two parts; a dose escalation part (phase I, first in- human (FIH)) and an expansion part (phase IIa).

The dose escalation part has two dose escalation arms: the first arm investigates a once every 3 weeks (1Q3W) dose schedule and the second one investigates a three administrations over 4 weeks (3Q4W) dose schedule.

The Expansion part of the trial, will further explore the recommended phase 2 dose of HuMax-AXL-ADC as determined in Part 1

Trial Arms

NameTypeDescriptionInterventions
HuMax-AXL-ADCExperimentalAll arms of the trial (both in escalation and expansion phase) will be administered HuMax-AXL-ADC

    Eligibility Criteria

    Inclusion Criteria:

    1. For the dose escalation part: Patients with selected, relapsed solid tumors who have failed available standard therapy or who are not candidates for standard therapy.

    2. For the expansion part: Patients with relapsed, advanced and/or metastatic solid tumors Patients must have measurable disease.

    3. Age ≥ 18 years.

    4. Acceptable renal function

    5. Acceptable liver function

    6. Acceptable hematological status

    7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

    8. Life expectancy of at least three months.

    9. Patients, both females and males, of childbearing/reproductive potential must agree to use adequate contraception while included in the trial and for six months after the last infusion of HuMax-AXL-ADC

    10. Patients must provide a signed informed consent form before any trial relates activities are carried out.

    Exclusion Criteria:

    1. Acute deep vein thrombosis or clinically relevant pulmonary embolism, not stable for at least 4 weeks prior to first IMP administration.

    2. Have clinically significant cardiac disease

    3. Known congestive heart failure and/ or a known decreased cardiac ejection fraction of < 45%. A baseline QT interval as corrected by Fridericia's formula (QTcF) > 480 msec, a complete left bundle branch block (defined as a QRS interval ≥ 120 msec in left bundle branch block form) or an incomplete left bundle branch block.

    4. Uncontrolled hypertension

    5. Have received granulocyte colony stimulating factor (G-CSF) or granulocyte/macrophage colony stimulating factor support 3 weeks prior to first IMP administration.

    6. Have received a cumulative dose of corticosteroid ≥ 150 mg prednisone (or equivalent doses of corticosteroids) within two weeks before the first Investigational Medicinal Product (IMP) administration.

    7. History of ≥ grade 3 allergic reactions to monoclonal antibody therapy as well as known or suspected allergy or intolerance to any agent given in the course of this trial.

    8. Major surgery within four weeks before first IMP administration.

    9. Any history of intracerebral arteriovenous malformation, cerebral aneurysm, brain metastases or stroke.

    10. Any anticancer therapy including; small molecules, immunotherapy, chemotherapy monoclonal antibodies or any other experimental drug within five half-lives but maximum four weeks before first infusion. Accepted exceptions are bisphosphonates, denosumab and gonadotropin-releasing hormone agonist or antagonist.

    11. Prior therapy with a conjugated or unconjugated auristatin derivative/vinca-binding site targeting payload.

    12. Radiotherapy within 14 days prior to first IMP administration.

    13. Known past or current malignancy other than inclusion diagnosis, except for:

    - Cervical carcinoma of Stage 1B or less.

    - Non-invasive basal cell or squamous cell skin carcinoma.

    - Non-invasive, superficial bladder cancer.

    - Prostate cancer with a current PSA level < 0.1 ng/mL.

    - Breast cancer in BRCA1 or BRCA2 positive ovarian cancer patients.

    - Any curable cancer with a complete response (CR) of > 2 years duration.

    14. Ongoing significant, uncontrolled medical condition including:

    o Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.

    15. Grade 2 or higher peripheral neuropathy.

    16. Clinically significant active viral, bacterial or fungal infection

    17. Known human immunodeficiency virus seropositivity.

    18. Known positive serology for hepatitis B (unless due to vaccination or passive immunization due to immunoglobulin therapy)

    19. Known positive serology for hepatitis C (unless due to immunoglobulin therapy)

    20. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the trial or evaluation of the trial result

    21. History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of IMP

    22. Body weight < 40 kg

    23. Women who are pregnant or breast feeding.

    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Dose Limiting Toxicities (DLTs)
    Time Frame:Dose Limiting Toxicities will be assessed from first treatment cycle (3 or 4 weeks)
    Safety Issue:
    Description:As this is a phase I trial the main objective is to assess recommended phase 2 dose of HuMax-AXL-ADC

    Secondary Outcome Measures

    Measure:Pharmacokinetic (PK) parameters, Cmax
    Time Frame:At end of trial (up to 10 months)
    Safety Issue:
    Description:
    Measure:Anti-tumor activity measured by tumor shrinkage (based on computerized tomography [CT]-scan evaluations), change in Cancer Antigen (CA) 125.
    Time Frame:At end of trial (up to 12 months)
    Safety Issue:
    Description:
    Measure:Pharmacokinetic (PK) parameters, AUC
    Time Frame:At end of trial (up to 10 months)
    Safety Issue:
    Description:

    Details

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

    Trial Keywords

      Last Updated

      December 22, 2016