Enapotamab Vedotin (HuMax-AXL-ADC) Safety Study in Patients With Solid Tumors
- 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.
- 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.
Salt Lake City
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 Phase I/II
Trial Type Treatment
- Primary ID GCT1021-01
- Secondary IDs NCI-2017-00143
- Clinicaltrials.gov ID NCT02988817