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

Inclusion Criteria:

- Patients with relapsed, 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 RECIST v1.1

• Age ≥ 18 years.
• Acceptable renal function.
• Acceptable liver function.
• Acceptable hematological status (hematologic support allowed under certain circumstances).
• Acceptable coagulation status.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of at least three months.
• A negative serum pregnancy test (if female and aged between 18-55 years old).
• Women who are pregnant or breast feeding are not to be included.
• Patients, both females and males, of reproductive potential must agree to use adequate contraception during and for six months after the last infusion of HuMax-TF-ADC.
• Following receipt of verbal and written information about the study, patients must provide signed informed consent before any study-related activity is carried out.

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).