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

NCT ID: NCT02988817

Last Updated: 2023-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 306 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-23
• Study Completion Date: 2021-11-12

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

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 2 dosing schedules: 1 dose every 3 weeks (1Q3W) dose regimen, and 3 doses every 4 weeks (3Q4W) dosing regimen.

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

Conditions

Ovarian Cancer; Cervical Cancer; Endometrial Cancer; Non Small Cell Lung Cancer (NSCLC); Thyroid Cancer; Melanoma; Sarcoma; Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Enapotamab vedotin (HuMax-AXL-ADC)

Participants in all cohorts of the trial (both in escalation and expansion phase) will be administered enapotamab vedotin (HuMax-AXL-ADC) intravenously (IV).

Group Type: EXPERIMENTAL

Enapotamab vedotin (HuMax-AXL-ADC)

Intervention Type: BIOLOGICAL

Enapotamab vedotin (HuMax-AXL-ADC) will be administered intravenously.

Interventions

Enapotamab vedotin (HuMax-AXL-ADC)

Enapotamab vedotin (HuMax-AXL-ADC) will be administered intravenously.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

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

2. Patients must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST).

3. For the expansion patients must provide a tumor tissue sample from archival tissue or fresh biopsy at enrolment

4. Age ≥ 18 years.

5. Acceptable renal function

6. Acceptable liver function

7. Acceptable hematological status

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

9. Life expectancy of at least three months.

10. 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

11. 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 prostate specific antigen (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 lactate dehydrogenase (LDH) ≥ 3 x upper limit normal (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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genmab

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ignace Vergote, Professor

Role: PRINCIPAL_INVESTIGATOR

Universitair Ziekenhuizen Leuven

Locations

Mayo Clinic - Phoenix

Phoenix, Arizona, United States

University of Colorado Hospital

Aurora, Colorado, United States

Yale University, Smilow Cancer Center at Yale New Haven Hospital

New Haven, Connecticut, United States

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Emory University School of Medicine, Winship Cancer Institute

Atlanta, Georgia, United States

University of Iowa

Iowa City, Iowa, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Washington University

St Louis, Missouri, United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Duke Cancer Institute

Durham, North Carolina, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Mary Crowley Cancer Research Center

Dallas, Texas, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, United States

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Universitair Ziekenhuizen Leuven

Leuven, Flemish Brabant, Belgium

Institut Roi Albert II - Cliniques Universitaires Saint Luc

Brussels, , Belgium

Universitair Ziekenhuis Brussel - Oncologisch Centrum

Jette, , Belgium

Medische oncologie, Oncologisch Centrum - AZ Groeninge

Kortrijk, , Belgium

U.Z. Leuven Gasthuisberg, Department of General Medical Oncology

Leuven, , Belgium

CHU de Liège, Medical Oncology et. Domaine Universitaire du Sart Tilman

Liège, , Belgium

Rigshospitalet, Copenhagen University Hospital

Copenhagen, , Denmark

The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

Amsterdam, , Netherlands

Leiden University Medical Centre

Leiden, , Netherlands

Erasmus MC, Medical Oncology

Rotterdam, , Netherlands

UMC Utrecht Cancer Center

Utrecht, , Netherlands

Hospital Unversitario Vall D'hebron

Barcelona, , Spain

Oncologia Mèdica/ Medical Oncology Department Institut Catalá d'Oncologia (ICO)

Barcelona, , Spain

University Hospital of Girona

Girona, , Spain

Hospital Universitario 12 Octubre Servicio de Oncologia Medica

Madrid, , Spain

Hospital Virgen de la Victoria

Málaga, , Spain

University Hospital Lozano Blesa, Aragón Health Research Institute (IIS Aragón)

Zaragoza, , Spain

University College London Hospitals

London, , United Kingdom

The Christie NHS Foundation Trust Clinical Trials Unit

Manchester, , United Kingdom

Sir Bobby Robson Clinical Trials Unit at the Northern Centre for Cancer Care, Freeman Hospital

Newcastle, , United Kingdom

The Royal Marsden Hospital

Sutton, , United Kingdom

Countries

United States; Belgium; Denmark; Netherlands; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-002243-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

211258

Identifier Type: OTHER

Identifier Source: secondary_id

GCT1021-01

Identifier Type: -

Identifier Source: org_study_id