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

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.