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

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

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.

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

Lead Organization
Genmab