First-in-human, open-label, dose-escalation trial with expansion cohorts to evaluate safety of Axl-specific antibody-drug conjugate (enapotamab vedotin, HuMax®-AXL-ADC) in patients with solid tumors.
- Conditions
- Patients with solid tumors10027655
- Registration Number
- NL-OMON48742
- Lead Sponsor
- Genmab
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 42
Patients with advanced and/or metastatic cancer:
- who have failed available standard treatments or
- who are not candidates for standard therapy., Patients must have measurable
disease according to Response
Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
Have an acceptable renal, liver, and hematological function., All patients must
provide a tumor tissue sample (Formalin Fixed Paraffin Embedded (FFPE) blocks /
slides) from archival tissue or fresh biopsy collected before Cycle 1, Day 1,
preferably derived from advanced disease stage., Age >= 18 years., Have an
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1., Life
expectancy of at least 3 months., Patients, both females and males, of
childbearing/reproductive potential must agree to use adequate contraception
during and for 6 months after the last infusion of enapotamab vedotin.,
Patients must provide a signed informed consent form.
Acute deep vein thrombosis or clinically relevant pulmonary embolism, not
stable for at least 4 weeks prior to first enapotamab vedotin administration.,
Have clinically significant cardiac disease, including:
- Onset of unstable angina within 6 months of signing the ICF.
- Acute myocardial infarction within 6 months of the signing the ICF., Known
congestive heart failure (Grade III or IV as classified by the New York Heart
Association); and/ or a known decreased cardiac ejection fraction of < 45%
and/or baseline QT interval as corrected by Fridericia*s formula (QTcF) > 480
msec or uncontrolled atrial fibrillation., Uncontrolled hypertension defined as
systolic blood pressure >=160 mmHg and/or diastolic blood pressure >=100 mmHg,
despite optimal medical management., Have received granulocyte colony
stimulating factor (G-CSF) or granulocyte/macrophage colony stimulating factor
support three weeks prior to first enapotamab vedotin administration., Have
received a cumulative dose of corticosteroid >= 150 mg prednisone (or equivalent
doses of corticosteroids) within two weeks before the first enapotamab vedotin
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 4 weeks before
first enapotamab vedotin 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 5 half-lives but
maximum 4 weeks before first infusion. Accepted exceptions are bisphosphonates,
denosumab and gonadotropin-releasing hormone agonist or antagonist, which can
be continued throughout the trial., Any prior therapy with a conjugated or
unconjugated auristatin derivative/vinca-binding site targeting payload.
(Previous treatment with vinca alkaloids is allowed in line with inclusion
criterion #1.), Radiotherapy within 14 days prior to first enapotamab vedotin
administration. (Palliative radiotherapy will be allowed)., 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:
- Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.,
Presence of >= grade 2 peripheral neuropathy., Clinically significant active
viral, bacterial or fungal infection requiring:
- I.v. treatment with anti-infective therapy that has been administered less
than two weeks prior to first dose, or
- Oral treatment with anti-infective therapy that has been administered less
than one week prior to first dose.
- Prophylactic anti-infective therapy, which is given without clinical
symptomatic is allowed (e.g. antibiotic prophylaxis prior to dental extraction,
etc.).
Known human immunodeficiency vi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• To determine the MTD and to establish the safety profile of enapotamab<br /><br>vedotin in a mixed population of patients with specified solid tumors. </p><br>
- Secondary Outcome Measures
Name Time Method <p>• To evaluate the safety laboratory parameters of enapotamab vedotin in a mixed<br /><br>population of patients with specified solid tumors.<br /><br>• To establish the PK profile and evaluate immunogenicity of enapotamab vedotin<br /><br>after single and multiple infusions.<br /><br>• To evaluate the antitumor activity of enapotamab vedotin in a mixed<br /><br>population of patients with specified solid tumors.<br /><br>• To evaluate Axl expression in tumor biopsies from a mixed population of<br /><br>patients with specified solid tumors.</p><br>