Patient case: 58-year-old female with endometrial cancer; genetic feature: PIK3R1

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

Summary: The purpose of the trial is to establish the tolerability of tisotumab vedotin (HuMax-TF-ADC) dosed three times every four weeks (3q4wk) in a mixed population of patients with specified solid tumors.

Detailed description: The study is conducted in two parts. In the Dose Escalation portion of the trial, subjects are enrolled into cohorts at increasing dose levels of tisotumab vedotin (HuMax-TF-ADC) in 28 day treatment cycles.
  The Cohort Expansion portion of the trial will further explore the recommended phase 2 dose of tisotumab vedotin (HuMax-TF-ADC) as determined in Part 1.

Eligibility: 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).

Relevance to patient case: not relevant