Tisotumab Vedotin (HuMax®-TF-ADC) Safety Study in Patients With Solid Tumors

Exclusion Criteria

• •Known past or current coagulation defects.
• •Diffuse alveolar hemorrhage from vasculitis.
• •Known bleeding diathesis.
• •Ongoing major bleeding.
• •Trauma with increased risk of life-threatening bleeding.
• •Have clinically significant cardiac disease.
• •A baseline QT interval as corrected by Fridericia's formula (QTcF) \> 450 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.
• •Therapeutic anti-coagulative or long term anti-platelet treatment except use of low dose acetylsalicylic acid (ASA) up to 81 mg/day and non-ASA nonsteroidal anti-inflammatory drugs (NSAIDs).
• •Have received granulocyte colony stimulating factor (G-CSF) or granulocyte/macrophage colony stimulating factor support within one week or pegylated G-CSF within two weeks before the Screening Visit.
• •Have received a cumulative dose of corticosteroid ≥ 150 mg (prednisone or equivalent doses of corticosteroids) within two weeks before the first infusion.
• •No dietary supplements allowed during the study period, except multivitamins, vitamin D and calcium.
• •Major surgery within six weeks or open biopsy within 14 days before drug infusion.
• •Plan for any major surgery during treatment period.
• •Patients not willing or able to have a pre-trial tumor biopsy taken (the screening biopsy can be omitted if archived material is available).
• •Presence or anticipated requirement of epidural catheter in relation to infusions (within 48 hours before and after dose of trial drug).
• •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 four weeks or five half lives, whichever is longest, before first infusion.
• •Prior treatment with bevacizumab within twelve weeks before the first infusion.
• •Prior therapy with a conjugated or unconjugated auristatin derivative.
• •Radiotherapy within 28 days prior to first dose.
• •Patients who have not recovered from symptomatic side effects of radiotherapy at the time of initiation of screening procedure.
• •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 BRACA2 positive ovarian cancer patients.
• •Any curable cancer with a complete response (CR) of \> 5 years duration.
• •Radiographic evidence of cavitating pulmonary lesions and tumor adjacent to or invading any large blood vessel unless approved by sponsor.
• •Ongoing, significant , uncontrolled medical condition.
• •Presence of peripheral neuropathy.
• •Active viral, bacterial or fungal infection requiring intravenous treatment with antimicrobial therapy starting less than four weeks prior to first dose.
• •Oral treatment with antimicrobial therapy starting less than two weeks prior to first dose.
• •Known human immunodeficiency virus seropositivity.
• •Positive serology (unless due to vaccination or passive immunization due to Ig therapy) for hepatitis B.
• •Positive serology for hepatitis C based on test at screening.
• •Inflammatory bowel disease including Crohn's disease and colitis ulcerosa.
• •Inflammatory lung disease including moderate and severe asthma and chronic obstructive pulmonary disease (COPD) requiring chronic medical therapy.
• •Ongoing acute or chronic inflammatory skin disease.
• •Active ocular surface disease at baseline (based on ophthalmological evaluation).
• •History of cicatricial conjunctivitis (as evaluated by an ophthalmologist).