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

Status: Active

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

Eligibility Criteria

Inclusion Criteria

  • 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.
  • For the expansion part: Patients with relapsed, advanced and/or metastatic solid tumors who are not candidates for standard therapy
  • Patients must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST).
  • For the expansion patients must provide a fresh tumor biopsy at enrolment
  • Age ≥ 18 years.
  • Acceptable renal function
  • Acceptable liver function
  • Acceptable hematological status
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Life expectancy of at least three months.
  • 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
  • Patients must provide a signed informed consent form before any trial relates activities are carried out.

Exclusion Criteria

  • Acute deep vein thrombosis or clinically relevant pulmonary embolism, not stable for at least 4 weeks prior to first IMP administration.
  • Have clinically significant cardiac disease
  • 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.
  • Uncontrolled hypertension
  • Have received granulocyte colony stimulating factor (G-CSF) or granulocyte/macrophage colony stimulating factor support 3 weeks prior to first IMP administration.
  • 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.
  • 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.
  • Major surgery within four weeks before first IMP administration.
  • Any history of intracerebral arteriovenous malformation, cerebral aneurysm, brain metastases or stroke.
  • 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.
  • Prior therapy with a conjugated or unconjugated auristatin derivative/vinca-binding site targeting payload.
  • Radiotherapy within 14 days prior to first IMP administration.
  • 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.
  • Melanoma patients with an LDH ≥ 3 x ULN.
  • Ongoing significant, uncontrolled medical condition including: o Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.
  • Grade 2 or higher peripheral neuropathy.
  • Clinically significant active viral, bacterial or fungal infection
  • Known human immunodeficiency virus seropositivity.
  • Known positive serology for hepatitis B (unless due to vaccination or passive immunization due to immunoglobulin therapy)
  • Known positive serology for hepatitis C (unless due to immunoglobulin therapy)
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the trial or evaluation of the trial result
  • 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
  • Body weight < 40 kg
  • Women who are pregnant or breast feeding.
  • Pulmonary hemorrhage or hemoptysis > 2.5 ml blood within 6 weeks unless cause has been addressed and is medically resolved.
  • History of acute pneumonitis.

Locations & Contacts

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: Active
Name Not Available

Colorado

Aurora
University of Colorado Hospital
Status: Active
Name Not Available

Connecticut

New Haven
Yale University
Status: Active
Name Not Available

Florida

Jacksonville
Mayo Clinic in Florida
Status: Active
Name Not Available

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Active
Name Not Available

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: Active
Name Not Available

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Name Not Available
Dana-Farber Cancer Institute
Status: Active
Name Not Available

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: Approved
Name Not Available

Minnesota

Rochester
Mayo Clinic
Status: Active
Name Not Available

New York

Buffalo
Roswell Park Cancer Institute
Status: Active
Name Not Available
New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: Active
Name Not Available
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Name Not Available

North Carolina

Durham
Duke University Medical Center
Status: Active
Name Not Available

Pennsylvania

Philadelphia
Fox Chase Cancer Center
Status: Active
Name Not Available

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Name Not Available

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Name Not Available

Trial Objectives and Outline

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

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Genmab

Trial IDs

Primary ID GCT1021-01
Secondary IDs NCI-2017-00143
Clinicaltrials.gov ID NCT02988817