Cervical Cancer
Conditions
Brief summary
A Single arm, Multicenter, International Trial of Tisotumab Vedotin (HuMax®-TF-ADC) in Previously Treated, Recurrent or Metastatic Cervical Cancer.
Detailed description
The purpose of the trial is to evaluate the efficacy and safety/tolerability of tisotumab vedotin in patients with previously treated, recurrent or metastatic cervical cancer. Tisotumab vedotin is an antibody-drug conjugate (ADC) targeting tissue factor (TF), a protein aberrantly expressed in a wide number of tumors including cervical cancer. Preliminary safety and efficacy data observed in a cohort of previously treated cervical cancer patients suggest a positive benefit risk profile for this population of high unmet need.
Interventions
All patients will be treated with tisotumab vedotin once every three weeks until progression or toxicity
Sponsors
Genmab
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Belgian Gynaecological Oncology Group
Gynecologic Oncology Group
Seagen Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with extra-pelvic metastatic or recurrent cervical cancer including squamous cell, adenocarcinoma or adenosquamous histology who have experienced disease progressed on standard of care chemotherapy in combination with bevacizumab, if eligible. * Measurable disease according to RECIST v1.1 as assessed by IRC. * Age ≥ 18 years. * 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 for patients of reproductive potential. * All patients must provide a fresh or archival biopsy during screening. * Following receipt of verbal and written information about the trial, patients must provide signed informed consent before any trial-related activity is carried out.
Exclusion criteria
* Have received no more than 2 prior systemic treatment regimens for recurrent or metastatic cervical cancer. * Known past or current coagulation defects leading to an increased risk of bleeding; * Ongoing major bleeding * Active ocular surface disease * Known past or current malignancy other than the inclusion diagnosis. * Peripheral neuropathy grade ≥ 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Confirmed Objective Response (OR) as Assessed by the Independent Review Committee (IRC) | From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 20 months) | The confirmed OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based upon RECIST v1.1, assessed by the IRC. The CR is disappearance of all target and non-target lesions and no new lesions. A confirmed CR is 2 CRs (CR-CR sequence) that were separated by at least 4 weeks with no evidence of progression in-between. The PR is ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion. A confirmed PR is PR-PR sequence or PR-CR sequence that were separated by at least 4 weeks. The intermediate missing (Not Evaluable \[NE\]) scan evaluations between response scan and confirmation scan were allowed, eg, PR-NE-PR and PR-NE-NE-PR was considered PR confirmed (a repeat scan not earlier than 4 weeks after initial scan documenting response). 95% CI was calculated using the Clopper-Pearson method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Confirmed OR as Assessed by the Investigator | From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months) | The confirmed OR is defined as best overall response of confirmed CR or confirmed PR based upon RECIST v1.1, assessed by the investigator. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as 2 CRs (CR-CR sequence) that were separated by at least 4 weeks with no evidence of progression in-between. The PR is defined as ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion. A confirmed PR is defined as PR-PR sequence or PR-CR sequence that were separated by at least 4 weeks. The intermediate missing (NE) scan evaluations between the response scan and the confirmation scan were allowed, eg, PR-NE-PR and PR-NE-NE-PR was considered PR confirmed (a repeat scan not earlier than 4 weeks after initial scan documenting response). 95% CI was calculated using the Clopper-Pearson method. |
| DOR as Assessed by the Investigator | From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months) | The DOR is defined as the duration from the first documented response of CR or PR (the start date of response, not the date when response was confirmed) to the date of the first documented PD verified by investigator or death. Based upon RECIST v1.1, the CR is defined as disappearance of all target and non-target lesions and no new lesions; the PR is defined as ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion; and the PD is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The DOR was estimated using Kaplan-Meier method. |
| Time to Response (TTR) as Assessed by the IRC | From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months) | The TTR is defined as the duration from the start of study drug to the first documented response of either CR or PR based on RECIST v1.1, assessed by the IRC. A confirmed CR is defined as 2 CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as 2 PRs (≥ 30% decrease in the sum of diameters of target lesions compared to baseline and no unequivocal progression of existing non-target lesions and no new lesion) or an un-confirmed PR and an un-confirmed CR or achieved PR-NE-PR or PR-NE-NE-PR that were separated by at least 4 weeks with no evidence of progression in-between. |
| TTR as Assessed by the Investigator | From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months) | The TTR is defined as the duration from the start of study drug to the first documented response of either CR or PR based on RECIST v1.1, assessed by the investigator. A confirmed CR is defined as 2 CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as 2 PRs (≥ 30% decrease in the sum of diameters of target lesions compared to baseline and no unequivocal progression of existing non-target lesions and no new lesion) or an un-confirmed PR and an un-confirmed CR or achieved PR-NE-PR or PR-NE-NE-PR that were separated by at least 4 weeks with no evidence of progression in-between. |
| Progression Free Survival (PFS) as Assessed by the IRC | From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months) | The PFS is defined as the time from the start of study drug until the first documentation of PD based on RECIST v1.1, as assessed by the IRC or death due to any cause, whichever occurred first. The PD based upon RECIST v1.1 is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The PFS was estimated using Kaplan-Meier method. |
| Duration of Response (DOR) as Assessed by the IRC | From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months) | The DOR is defined as the duration from the first documented response of CR or PR (the start date of response, not the date when response was confirmed) to the date of the first documented progression disease (PD) verified by IRC or death. Based upon RECIST v1.1, the CR is defined as disappearance of all target and non-target lesions and no new lesions; the PR is defined as ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion; and the PD is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The DOR was estimated using Kaplan-Meier method. |
| Overall Survival (OS) | From Day 1 until death or withdrawal from the study, whichever occurred first (approximately 49 months) | The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | From Day 1 through 30 days after the last dose of study drug (approximately 49 months) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is defined as an AE that meets one of the following criteria: fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above \[medical and scientific judgment must be exercised in deciding whether an AE is medically important\]); required inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE occurring or worsening between the first dose of tisotumab vedotin and 30 days after the last dose received. |
| Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | From Day 1 through 30 days after the last dose of study drug (approximately 49 months) | Laboratory abnormalities that induced clinical signs or symptoms, required concomitant therapy or required changes during treatment emergent period were reported as TEAEs. Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. |
| Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE) | Predose and end of infusion of Cycle 1 Day 1 (C1D1) and Cycle 6 Day 1 (C6D1) | Plasma concentrations of HuMax-TF, HuMax-TF-ADC, and Free MMAE measures on Cycle 1 Day 1 (predose and end of infusion) and Cycle 6 Day 1 (predose and end of infusion) are reported. |
| Number of Participants With Positive Anti-drug Antibodies (ADA) to Tisotumab Vedotin | Predose of each treatment cycle (Cycle 1 to 21) and end of treatment visit (approximately 49 months) | Number of participants with positive ADA titer to tisotumab vedotin at baseline and post-baseline are reported. Baseline is defined as the latest available measurement made before the first dose of tisotumab vedotin. For post-baseline results, a participant was considered ADA positive if either ADA is negative at baseline and at least one post-baseline result is positive or positive at baseline and at least one positive post-baseline result with a titer higher than baseline. |
| PFS as Assessed by the Investigator | From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months) | The PFS is defined as the time from the start of study drug until the first documentation of PD based on RECIST v1.1, as assessed by the investigator or death due to any cause, whichever occurred first. The PD based upon RECIST v1.1 is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The PFS was estimated using Kaplan-Meier method. |
Countries
Belgium, Czechia, Denmark, Germany, Italy, Spain, Sweden, United States
Participant flow
Recruitment details
This study was conducted in Europe and the US.
Pre-assignment details
A 102 participants with Recurrent or Metastatic Cervical Cancer were enrolled in the study and out of which 101 participants received study treatment. These participants were assessed until the participant experienced IRC-verified disease progression, started new anti-cancer therapy, discontinued the trial, or died.
Participants by arm
| Arm | Count |
|---|---|
| Tisotumab Vedotin Participants received IV tisotumab vedotin 2.0 mg/kg Q3W until radiographic disease progression verified by the IRC, unacceptable AEs requiring drug discontinuation, withdrawal of consent, lost to follow up or death, whichever occurred first. | 101 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 85 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Not treated | 1 |
| Overall Study | Reason Not Specified | 9 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Tisotumab Vedotin |
|---|---|
| Age, Continuous | 50.66 Years STANDARD_DEVIATION 10.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 95 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 3 Participants |
| Race (NIH/OMB) White | 95 Participants |
| Sex: Female, Male Female | 101 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 86 / 101 |
| other Total, other adverse events | 99 / 101 |
| serious Total, serious adverse events | 44 / 101 |
Outcome results
Primary
Percentage of Participants With Confirmed Objective Response (OR) as Assessed by the Independent Review Committee (IRC)
The confirmed OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based upon RECIST v1.1, assessed by the IRC. The CR is disappearance of all target and non-target lesions and no new lesions. A confirmed CR is 2 CRs (CR-CR sequence) that were separated by at least 4 weeks with no evidence of progression in-between. The PR is ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion. A confirmed PR is PR-PR sequence or PR-CR sequence that were separated by at least 4 weeks. The intermediate missing (Not Evaluable \[NE\]) scan evaluations between response scan and confirmation scan were allowed, eg, PR-NE-PR and PR-NE-NE-PR was considered PR confirmed (a repeat scan not earlier than 4 weeks after initial scan documenting response). 95% CI was calculated using the Clopper-Pearson method.
Time frame: From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 20 months)
Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tisotumab Vedotin | Percentage of Participants With Confirmed Objective Response (OR) as Assessed by the Independent Review Committee (IRC) | 23.8 Percentage of Participants |
p-value: 0.0002one-sided exact test
Secondary
DOR as Assessed by the Investigator
The DOR is defined as the duration from the first documented response of CR or PR (the start date of response, not the date when response was confirmed) to the date of the first documented PD verified by investigator or death. Based upon RECIST v1.1, the CR is defined as disappearance of all target and non-target lesions and no new lesions; the PR is defined as ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion; and the PD is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The DOR was estimated using Kaplan-Meier method.
Time frame: From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)
Population: FAS included all participants who received at least 1 dose of tisotumab vedotin. The DOR was analyzed for those participants in FAS who achieved confirmed OR, as assessed by the investigator.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisotumab Vedotin | DOR as Assessed by the Investigator | 8.2 Months |
Secondary
Duration of Response (DOR) as Assessed by the IRC
The DOR is defined as the duration from the first documented response of CR or PR (the start date of response, not the date when response was confirmed) to the date of the first documented progression disease (PD) verified by IRC or death. Based upon RECIST v1.1, the CR is defined as disappearance of all target and non-target lesions and no new lesions; the PR is defined as ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion; and the PD is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The DOR was estimated using Kaplan-Meier method.
Time frame: From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)
Population: FAS included all participants who received at least 1 dose of tisotumab vedotin. The DOR was analyzed for those participants in FAS who achieved confirmed OR, as assessed by the IRC.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisotumab Vedotin | Duration of Response (DOR) as Assessed by the IRC | 8.3 Months |
Secondary
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Laboratory abnormalities that induced clinical signs or symptoms, required concomitant therapy or required changes during treatment emergent period were reported as TEAEs. Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported.
Time frame: From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood creatinine increased | 2 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | C-reactive protein increased | 2 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | International normalised ratio increased | 2 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Lymphocyte count decreased | 2 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Alanine aminotransferase increased | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Aspartate aminotransferase increased | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood alkaline phosphatase increased | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood bicarbonate decreased | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood creatine phosphokinase increased | 2 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood potassium decreased | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Creatinine renal clearance decreased | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Platelet count decreased | 2 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Prothrombin time prolonged | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | White blood cell count decreased | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyperthyroidism | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypothyroidism | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypertransaminasaemia | 3 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyperbilirubinaemia | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Haematuria | 10 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Anaemia | 34 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Neutropenia | 4 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Iron deficiency anaemia | 3 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Leukocytosis | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Leukopenia | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Thrombocytopenia | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Thrombocytosis | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypokalaemia | 6 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypomagnesaemia | 6 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypocalcaemia | 4 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyperglycaemia | 3 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypercreatininaemia | 2 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyperuricaemia | 2 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypercalcaemia | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypernatraemia | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypoalbuminaemia | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyponatraemia | 1 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Activated partial thromboplastin time prolonged | 3 Participants |
| Tisotumab Vedotin | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Neutrophil count decreased | 3 Participants |
Secondary
Number of Participants With Positive Anti-drug Antibodies (ADA) to Tisotumab Vedotin
Number of participants with positive ADA titer to tisotumab vedotin at baseline and post-baseline are reported. Baseline is defined as the latest available measurement made before the first dose of tisotumab vedotin. For post-baseline results, a participant was considered ADA positive if either ADA is negative at baseline and at least one post-baseline result is positive or positive at baseline and at least one positive post-baseline result with a titer higher than baseline.
Time frame: Predose of each treatment cycle (Cycle 1 to 21) and end of treatment visit (approximately 49 months)
Population: Participants in FAS (received at least 1 dose of tisotumab vedotin) and who had ADA results at baseline and post-baseline are analyzed for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tisotumab Vedotin | Number of Participants With Positive Anti-drug Antibodies (ADA) to Tisotumab Vedotin | ADA positive at Baseline | 2 Participants |
| Tisotumab Vedotin | Number of Participants With Positive Anti-drug Antibodies (ADA) to Tisotumab Vedotin | ADA positive at post-baseline | 5 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is defined as an AE that meets one of the following criteria: fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above \[medical and scientific judgment must be exercised in deciding whether an AE is medically important\]); required inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE occurring or worsening between the first dose of tisotumab vedotin and 30 days after the last dose received.
Time frame: From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tisotumab Vedotin | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE | 101 Participants |
| Tisotumab Vedotin | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAE | 44 Participants |
Secondary
Overall Survival (OS)
The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method.
Time frame: From Day 1 until death or withdrawal from the study, whichever occurred first (approximately 49 months)
Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisotumab Vedotin | Overall Survival (OS) | 12.3 Months |
Secondary
Percentage of Participants With Confirmed OR as Assessed by the Investigator
The confirmed OR is defined as best overall response of confirmed CR or confirmed PR based upon RECIST v1.1, assessed by the investigator. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as 2 CRs (CR-CR sequence) that were separated by at least 4 weeks with no evidence of progression in-between. The PR is defined as ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion. A confirmed PR is defined as PR-PR sequence or PR-CR sequence that were separated by at least 4 weeks. The intermediate missing (NE) scan evaluations between the response scan and the confirmation scan were allowed, eg, PR-NE-PR and PR-NE-NE-PR was considered PR confirmed (a repeat scan not earlier than 4 weeks after initial scan documenting response). 95% CI was calculated using the Clopper-Pearson method.
Time frame: From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)
Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tisotumab Vedotin | Percentage of Participants With Confirmed OR as Assessed by the Investigator | 20.8 Percentage of Participants |
Secondary
PFS as Assessed by the Investigator
The PFS is defined as the time from the start of study drug until the first documentation of PD based on RECIST v1.1, as assessed by the investigator or death due to any cause, whichever occurred first. The PD based upon RECIST v1.1 is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The PFS was estimated using Kaplan-Meier method.
Time frame: From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)
Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisotumab Vedotin | PFS as Assessed by the Investigator | 4.1 Months |
Secondary
Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE)
Plasma concentrations of HuMax-TF, HuMax-TF-ADC, and Free MMAE measures on Cycle 1 Day 1 (predose and end of infusion) and Cycle 6 Day 1 (predose and end of infusion) are reported.
Time frame: Predose and end of infusion of Cycle 1 Day 1 (C1D1) and Cycle 6 Day 1 (C6D1)
Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tisotumab Vedotin | Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE) | HuMax-TF (C1D1-predose) | 163.48 ng/mL | Geometric Coefficient of Variation 60.7 |
| Tisotumab Vedotin | Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE) | HuMax-TF (C1D1-end of infusion) | 41691.0 ng/mL | Geometric Coefficient of Variation 68.02 |
| Tisotumab Vedotin | Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE) | HuMax-TF (C6D1-predose) | 150.0 ng/mL | Geometric Coefficient of Variation 0 |
| Tisotumab Vedotin | Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE) | HuMax-TF (C6D1-end of infusion) | 36941 ng/mL | Geometric Coefficient of Variation 25.88 |
| Tisotumab Vedotin | Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE) | HuMax-TF-ADC (C1D1-predose) | 30.0 ng/mL | Geometric Coefficient of Variation 0 |
| Tisotumab Vedotin | Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE) | HuMax-TF-ADC (C1D1-end of infusion) | 38105 ng/mL | Geometric Coefficient of Variation 92.62 |
| Tisotumab Vedotin | Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE) | HuMax-TF-ADC (C6D1-predose) | 30.0 ng/mL | Geometric Coefficient of Variation 0 |
| Tisotumab Vedotin | Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE) | HuMax-TF-ADC (C6D1-end of infusion) | 36270.0 ng/mL | Geometric Coefficient of Variation 28.29 |
| Tisotumab Vedotin | Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE) | MMAE (C1D1-predose) | 12.50 ng/mL | Geometric Coefficient of Variation 0 |
| Tisotumab Vedotin | Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE) | MMAE (C1D1-end of infusion) | 171.27 ng/mL | Geometric Coefficient of Variation 102.05 |
| Tisotumab Vedotin | Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE) | MMAE (C6D1-predose) | 46.71 ng/mL | Geometric Coefficient of Variation 146.11 |
| Tisotumab Vedotin | Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE) | MMAE (C6D1-end of infusion) | 177.46 ng/mL | Geometric Coefficient of Variation 82.62 |
Secondary
Progression Free Survival (PFS) as Assessed by the IRC
The PFS is defined as the time from the start of study drug until the first documentation of PD based on RECIST v1.1, as assessed by the IRC or death due to any cause, whichever occurred first. The PD based upon RECIST v1.1 is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The PFS was estimated using Kaplan-Meier method.
Time frame: From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)
Population: FAS included all participants who received at least 1 dose of tisotumab vedotin.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisotumab Vedotin | Progression Free Survival (PFS) as Assessed by the IRC | 4.2 Months |
Secondary
Time to Response (TTR) as Assessed by the IRC
The TTR is defined as the duration from the start of study drug to the first documented response of either CR or PR based on RECIST v1.1, assessed by the IRC. A confirmed CR is defined as 2 CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as 2 PRs (≥ 30% decrease in the sum of diameters of target lesions compared to baseline and no unequivocal progression of existing non-target lesions and no new lesion) or an un-confirmed PR and an un-confirmed CR or achieved PR-NE-PR or PR-NE-NE-PR that were separated by at least 4 weeks with no evidence of progression in-between.
Time frame: From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)
Population: FAS included all participants who received at least 1 dose of tisotumab vedotin. The TTR was analyzed for those participants in FAS who achieved confirmed OR, as assessed by the IRC.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisotumab Vedotin | Time to Response (TTR) as Assessed by the IRC | 1.4 Months |
Secondary
TTR as Assessed by the Investigator
The TTR is defined as the duration from the start of study drug to the first documented response of either CR or PR based on RECIST v1.1, assessed by the investigator. A confirmed CR is defined as 2 CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as 2 PRs (≥ 30% decrease in the sum of diameters of target lesions compared to baseline and no unequivocal progression of existing non-target lesions and no new lesion) or an un-confirmed PR and an un-confirmed CR or achieved PR-NE-PR or PR-NE-NE-PR that were separated by at least 4 weeks with no evidence of progression in-between.
Time frame: From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)
Population: FAS included all participants who received at least 1 dose of tisotumab vedotin. The TTR was analyzed for those participants in FAS who achieved confirmed OR, as assessed by the investigator.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tisotumab Vedotin | TTR as Assessed by the Investigator | 1.4 Months |