Tisotumab Vedotin Continued Treatment in Patients With Solid Tumors.

Study Overview
=================
Brief Summary
-----------------
The purpose of the trial is to evaluate efficacy and safety of continued treatment with tisotumab vedotin.

Detailed Description
-----------------
This is an open-label, multicenter trial to collect long-term safety and efficacy data and to provide ongoing access to tisotumab vedotin for patients with solid tumors who have completed a tisotumab vedotin base trial.

Official Title
-----------------
A Multi-center, Open-label Trial Investigating the Efficacy and Safety of Continued Treatment With Tisotumab Vedotin in Patients With Solid Tumors Known to Express Tissue Factor.

Conditions
-----------------
Ovary Cancer, Cervix Cancer, Endometrium Cancer, Bladder Cancer, Prostate Cancer, Esophagus Cancer, Lung Cancer, Nonsmall Cell, Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
-----------------
* Drug: Tisotumab Vedotin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must have either: completed the base trial and have shown a clinical benefit of SD or better and have never met any withdrawal criteria as defined in the tisotumab vedotin base protocol, or not completed treatment as defined in the base protocol for reasons that are not considered critical and unmanageable for the safety of the patient (as evaluated by the investigator and/or the sponsor) and the patient clearly showed response of PR or better. Patients must not have experienced radiographic disease progression or clinical signs of symptoms of instability requiring urgent intervention. Patients must not have received any other anti-cancer treatment (including surgery, radiation or systemic chemotherapy) since the base trial. Acceptable renal function Acceptable liver function Acceptable hematological status Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. A negative serum pregnancy test (if female and aged between 18-55 years old). Patients, both females and males, of reproductive potential must agree to use adequate contraception during and for six months after the last infusion of tisotumab vedotin. Adequate contraception for women is defined as hormonal birth control or an intrauterine device (safe hormonal contraceptives include contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release). In countries where two highly effective methods of contraception are required this will be an inclusion criterion. Male patients must be willing to use a latex condom during any sexual contact with females of childbearing potential during and for six months after the last infusion of tisotumab vedotin, even after having undergone a successful vasectomy. In order to be considered as sterilized or infertile, a patient must have undergone surgical sterilization (vasectomy/bilateral tubectomy; hysterectomy and bilateral ovariectomy) or be postmenopausal (12 months or more with no period prior to enrolment). Following receipt of verbal and written information about the trial, patients must provide signed informed consent before any trial-related activity is carried out. Acceptable coagulation status as defined in the applicable base protocol GEN701: Acceptable coagulation status: International normalized ratio (INR) ≤ 1.2 (without anticoagulant therapy), and activated partial thromboplastin time (aPTT) ≤ 1.25 ULN; patients on stable doses of therapeutic anti-coagulative treatment for ≥ 8 weeks (e.g., warfarin) must have an INR < 3. GEN702: Acceptable coagulation status defined as: INR ≤ 1.2 (without anticoagulant therapy), and aPTT ≤ ULN. Exclusion Criteria: Presence of CTCAE (Common Terminology Criteria for Adverse Events) grade ≥ 2 peripheral neuropathy. Clinically significant active viral, bacterial or fungal infection requiring: Intravenous treatment with anti-infective therapy that has been administered less than two weeks prior to first dose in this trial, or Oral treatment with anti-infective therapy that has been administered less than one week prior to first dose in this trial. Prophylactic anti-infective therapy, which is given without clinical symptoms is allowed. Ongoing acute or chronic inflammatory skin disease. Women who are breast feeding.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tisotumab Vedotin<br>All patients will be administered tisotumab vedotin (HuMax-TF-ADC) in 21 day treatment cycles. | Drug: Tisotumab Vedotin<br>* All patients in the trial will be administered tisotumab vedotin (HuMax-TF-ADC).<br>* Other names: TIVDAK;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced a Treatment Emergent Adverse Event (TEAE) | An adverse event (AE) is any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Treatment emergent adverse event (TEAE) is an AE occurring on or after the first dose of study medication or worsening during treatment period. | Day 1 to Week 24 plus 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective Response was investigator-assessed based on the Response Evaluation Criteria In Solid Tumors version 1.1 [RECIST 1.1] criteria. The best overall response was reported for each participant. | Day 1 to Week 24 plus 30 days | 
| Number of Participants With Increased Cancer Antigen (CA 125) Levels | The number of participants with ovarian cancer whose levels of CA125 Antigen had increased since the end of the base trial are presented. | Day 1 to Week 24 plus 30 days | 
| Number of Participants With Increased Prostate Specific Antigen (PSA) | The number of participants with prostate cancer whose levels of PSA had increased since the end of the base trial are presented. | Day 1 to Week 24 plus 30 days |