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

Genmab

Status and phase: Completed; Phase 2; Phase 1

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

Treatments: Biological: Enapotamab vedotin (HuMax-AXL-ADC)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02988817

211258 (Other Identifier)

GCT1021-01

2016-002243-42 (EudraCT Number)

Details and patient eligibility

About

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

Full 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.

Enrollment: 306 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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306 participants in 1 patient group

Enapotamab vedotin (HuMax-AXL-ADC)

Experimental group

Description:

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

Treatment:

Biological: Enapotamab vedotin (HuMax-AXL-ADC)