Bladder Cancer, Cervix Cancer, Endometrium Cancer, Esophagus Cancer, Lung Cancer, Nonsmall Cell, Ovary Cancer, Prostate Cancer, Squamous Cell Carcinoma of the Head and Neck
Conditions
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.
Interventions
All patients in the trial will be administered tisotumab vedotin (HuMax-TF-ADC).
Sponsors
Genmab
Seagen Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have either: 1. 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 2. 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. 1. 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. 2. 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. 3. 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 1. 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. 2. 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: 1. Intravenous treatment with anti-infective therapy that has been administered less than two weeks prior to first dose in this trial, or 2. Oral treatment with anti-infective therapy that has been administered less than one week prior to first dose in this trial. 3. Prophylactic anti-infective therapy, which is given without clinical symptoms is allowed. * Ongoing acute or chronic inflammatory skin disease. * Women who are breast feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Treatment Emergent Adverse Event (TEAE) | Day 1 to Week 24 plus 30 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Day 1 to Week 24 plus 30 days | 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. |
| Number of Participants With Increased Cancer Antigen (CA 125) Levels | Day 1 to Week 24 plus 30 days | The number of participants with ovarian cancer whose levels of CA125 Antigen had increased since the end of the base trial are presented. |
| Number of Participants With Increased Prostate Specific Antigen (PSA) | Day 1 to Week 24 plus 30 days | The number of participants with prostate cancer whose levels of PSA had increased since the end of the base trial are presented. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
All participants entered the trial following completion of other tisotumab vedotin trials such as GEN701 and GEN702. A total of 5 participants took part in the trial at 3 sites in the United Kingdom and 1 site in the United States from 23 August 2017 to 10 January 2019.
Pre-assignment details
Six participants were screened, 5 of which were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Tisotumab Vedotin Tisotumab vedotin was administered as an intravenous (IV) infusion on Day 1 of each 21-day cycle (once every 3 weeks). The trial ran until the investigator determined that the participant was no longer benefiting from treatment (ie, disease progression or unacceptable toxicity had occurred), the trial was terminated by the sponsor, or the participant withdrew consent. Each participant received the same dose that they were exposed to in the previous base trial. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Progressive Disease | 4 |
Baseline characteristics
| Characteristic | Tisotumab Vedotin |
|---|---|
| Age, Continuous | 50.4 years STANDARD_DEVIATION 10.46 |
| Age, Customized 85 years and over | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants |
| Age, Customized Adults (18-64 years) | 5 Participants |
| Age, Customized Children (2-11 years) | 0 Participants |
| Age, Customized From 65-84 years | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 0 Participants |
| Age, Customized In utero | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
Primary
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.
Time frame: Day 1 to Week 24 plus 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tisotumab Vedotin | Number of Participants Who Experienced a Treatment Emergent Adverse Event (TEAE) | 5 Participants |
Secondary
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.
Time frame: Day 1 to Week 24 plus 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tisotumab Vedotin | Number of Participants With Increased Cancer Antigen (CA 125) Levels | 1 Participants |
Secondary
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.
Time frame: Day 1 to Week 24 plus 30 days
Population: No participants with prostate cancer participated in this trial.
Secondary
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.
Time frame: Day 1 to Week 24 plus 30 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tisotumab Vedotin | Objective Response Rate | Partial Response | 2 Participants |
| Tisotumab Vedotin | Objective Response Rate | Complete Response | 0 Participants |
| Tisotumab Vedotin | Objective Response Rate | Stable Disease | 2 Participants |
| Tisotumab Vedotin | Objective Response Rate | Progressive Disease | 1 Participants |