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Enapotamab Vedotin (HuMax-AXL-ADC) Safety Study in Patients With 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. Read our disclaimer for details. Identifier: NCT02988817
Recruitment Status : Active, not recruiting
First Posted : December 9, 2016
Last Update Posted : July 2, 2021
Information provided by (Responsible Party):

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Ovarian Cancer Cervical Cancer Endometrial Cancer Non Small Cell Lung Cancer Thyroid Cancer Melanoma Sarcoma Biological: Enapotamab vedotin (HuMax-AXL-ADC) Phase 1 Phase 2

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) dosing schedule and the second arm investigates a three administrations over 4 weeks (3Q4W) dosing schedule.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 374 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of Axl-specific Antibody-drug Conjugate (Enapotamab Vedotin, HuMax®-AXL-ADC) in Patients With Solid Tumors
Actual Study Start Date : December 2016
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : December 2021

Arm Intervention/treatment
Experimental: Enapotamab vedotin (HuMax-AXL-ADC)
All arms of the trial (both in escalation and expansion phase) will be administered enapotamab vedotin (HuMax-AXL-ADC)
Biological: Enapotamab vedotin (HuMax-AXL-ADC)
All arms of the trial (both in escalation and expansion phase) will be administered enapotamab vedotin (HuMax-AXL-ADC)

Primary Outcome Measures :
  1. Dose Limiting Toxicities (DLTs) [ Time Frame: Dose Limiting Toxicities will be assessed from first treatment cycle (3 or 4 weeks) ]
    As this is a phase I trial the main objective is to assess the recommended phase 2 dose of enapotamab vedotin (HuMax-AXL-ADC)

  2. Adverse events (AEs) [ Time Frame: At end of trial (up to 24 months) ]
    As this is a phase I trial the main objective is to assess the safety and tolerability of enapotamab vedotin (HuMax-AXL-ADC) throughout the treatment periods of the patients participating in the trial.

Secondary Outcome Measures :
  1. Pharmacokinetic (PK) parameters, Cmax [ Time Frame: At end of trial (up to 10 months) ]
  2. 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) ]
  3. Pharmacokinetic (PK) parameters, AUC [ Time Frame: At end of trial (up to 10 months) ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 who are not candidates for standard therapy
  3. Patients must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST).
  4. For the expansion patients must provide a fresh tumor biopsy at enrolment
  5. Age ≥ 18 years.
  6. Acceptable renal function
  7. Acceptable liver function
  8. Acceptable hematological status
  9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  10. Life expectancy of at least three months.
  11. 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
  12. 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. Melanoma patients with an LDH ≥ 3 x ULN.
  15. Ongoing significant, uncontrolled medical condition including:

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

  16. Grade 2 or higher peripheral neuropathy.
  17. Clinically significant active viral, bacterial or fungal infection
  18. Known human immunodeficiency virus seropositivity.
  19. Known positive serology for hepatitis B (unless due to vaccination or passive immunization due to immunoglobulin therapy)
  20. Known positive serology for hepatitis C (unless due to immunoglobulin therapy)
  21. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the trial or evaluation of the trial result
  22. 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
  23. Body weight < 40 kg
  24. Women who are pregnant or breast feeding.
  25. Pulmonary hemorrhage or hemoptysis > 2.5 ml blood within 6 weeks unless cause has been addressed and is medically resolved.
  26. History of acute pneumonitis.

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): NCT02988817

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Sponsors and Collaborators
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Principal Investigator: Ignace Vergote, Professor Universitair Ziekenhuizen Leuven
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Responsible Party: Genmab Identifier: NCT02988817    
Other Study ID Numbers: GCT1021-01
First Posted: December 9, 2016    Key Record Dates
Last Update Posted: July 2, 2021
Last Verified: June 2021
Additional relevant MeSH terms:
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Endometrial Neoplasms
Thyroid Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Uterine Neoplasms
Uterine Diseases
Head and Neck Neoplasms
Thyroid Diseases