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).