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HuMax-AXL-ADC Safety Study in Patients With Solid Tumors

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ClinicalTrials.gov Identifier: NCT02988817
Recruitment Status : Recruiting
First Posted : December 9, 2016
Last Update Posted : November 28, 2018
Sponsor:
Information provided by (Responsible Party):
Genmab

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: 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


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 292 participants
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 (HuMax®-AXL-ADC) in Patients With Solid Tumors
Actual Study Start Date : December 2016
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : June 2021


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


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 ClinicalTrials.gov identifier (NCT number): NCT02988817


Contacts
Contact: Mika Bohlbro +45 3377 9569 m.bohlbro@genmab.com

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Sponsors and Collaborators
Genmab
Investigators
Principal Investigator: Ignace Vergote, Professor Universitair Ziekenhuizen Leuven

Responsible Party: Genmab
ClinicalTrials.gov Identifier: NCT02988817     History of Changes
Other Study ID Numbers: GCT1021-01
First Posted: December 9, 2016    Key Record Dates
Last Update Posted: November 28, 2018
Last Verified: November 2018

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Uterine Cervical Neoplasms
Thyroid Neoplasms
Endometrial Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Endocrine Gland Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases
Thyroid Diseases