Bladder Cancer, Cervix Cancer, Endometrium Cancer, Esophagus Cancer, Lung Cancer (NSCLC), Ovary Cancer, Prostate Cancer (CRPC)
Conditions
Keywords
ovary cancer, cervix cancer, endometrium cancer, bladder cancer, prostate cancer (CRPC), esophagus cancer, lung cancer (NSCLC)
Brief 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.
Interventions
Sponsors
Genmab
Seagen Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants Who Experience at Least One Adverse Event (AE) | Baseline to end of follow-up; maximum time of follow-up was 24 weeks | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. |
| Part 2: Number of Participants Who Experience at Least One Adverse Event (AE) | Baseline to end of trial (Part 2), up to 36 weeks | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. |
| Part 1: Number of Participants Who Experienced at Least One or More Serious Adverse Event (SAE) | Baseline to end of follow-up; maximum time of follow-up was 24 weeks | A SAE is defined as an AE that met one or more of the following criteria/outcomes which were classified as serious: Required inpatient hospitalization or prolongation of existing hospitalization. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Was a congenital anomaly/birth defect. Medically important determined by the investigator. Resulted in death. Was life-threatening. |
| Part 2: Number of Participants Reporting One or More Serious Adverse Events (SAE) | Baseline to end of trial (Part 2), up to 36 weeks | A SAE is defined as an AE that met one or more of the following criteria/outcomes which were classified as serious: Required inpatient hospitalization or prolongation of existing hospitalization. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Was a congenital anomaly/birth defect. Medically important determined by the investigator. Resulted in death. Was life-threatening. |
| Part 1: Number of Participants Reporting One or More Infusion-related Adverse Events | Day 1, Day 8 & Day 15 (+1 day) until end of treatment (Part 1), approximately 48 weeks | An infusion-related adverse event (AE) was defined as an AE occurring during infusion where the onset date and time of the event occurred within infusion time (+24 hours), and the event was judged as related to tisotumab vedotin by the investigator. |
| Part 2: Number of Participants Reporting One or More Infusion-related Adverse Events | Day 1, Day 8 & Day 15 (+1 day) until end of trial (Part 2), up to 36 weeks | An infusion-related adverse event (AE) was defined as an AE occurring during infusion where the onset date and time of the event occurred within infusion time (+24 hours), and the event was judged as related to tisotumab vedotin by the investigator. |
| Part 1: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events | Baseline to end of follow-up; maximum time of follow-up was 24 weeks | A CTCAE AE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator. |
| Part 2: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events | Baseline to end of trial (Part 2), up to 36 weeks | A CTCAE AE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator. |
| Part 1: Number of Participants Reporting One or More Treatment-related Adverse Events | Baseline to end of follow-up; maximum time of follow-up was 24 weeks | A treatment-related AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; which has a causal relationship with the treatment. |
| Part 2: Number of Participants Reporting One or More Treatment-related Adverse Events | Baseline to end of trial (Part 2), up to 36 weeks | A treatment-related AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; which has a causal relationship with the treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Tisotumab Vedotin (HuMax-TF-ADC) | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8 and 15, + 24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), +168 hours 3rd infusion (Day 22) of Cycle 1 | Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase. |
| Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 | — |
| Part 2: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 | — |
| Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Tisotumab Vedotin (HuMax-TF-ADC) | Before infusion of Day 1, 8 and 15 of Cycle 1 | Data is only available for Part 1, for Part 2 inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3. |
| Part 1: Terminal Phase Elimination Half-life (T1/2) for Tisotumab Vedotin (HuMax-TF-ADC) | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 | Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore t1/2 could not be determined. |
| Part 1: Total Clearance (CL) of Tisotumab Vedotin (HuMax-TF-ADC) | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 | Data is only available for Part 1, for Part 2 inadequate pharmacokinetic samples were collected after the third dose to define a terminal phase, and therefore CL could not be determined. |
| Part 1: Apparent Volume of Distribution (Vz) for Tisotumab Vedotin (HuMax-TF-ADC) | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 | Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore Vz could not be determined. |
| Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 | — |
| Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Total HuMax-TF (Conjugated and Non-conjugated) | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 | Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase. |
| Part 1: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 | — |
| Part 2: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 | — |
| Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Part 1: Terminal Phase Elimination Half-life (T1/2) for Total HuMax-TF (Conjugated and Non-conjugated) | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 | Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore t1/2 could not be determined. |
| Part 1 and Part 2: Total Clearance (CL) of Total HuMax-TF (Conjugated and Non-conjugated) | 0 to 2 hours post-dose on days 1, 8, 15, +24 hrs 1st infusion, +24 hrs 3rd infusion, +72 hrs 3rd infusion, +168 hrs 3rd infusion (Part 1) and 0 to 2 hours post-dose on day 1, and pre-dose days 8 and 15 (Part 2) of Cycle 1 | CL could not be estimated for Part 1 or Part 2 participants due to insufficient number of samples taken. |
| Part 1 & Part 2: Apparent Volume of Distribution (Vz) for Total HuMax-TF (Conjugated and Non-conjugated) | 0 to 2 hours post-dose on days 1, 8, 15, +24 hrs 1st infusion, +24 hrs 3rd infusion, +72 hrs 3rd infusion, +168 hrs 3rd infusion (Part 1) and 0 to 2 hours post-dose on day 1, and pre-dose days 8 and 15 (Part 2) of Cycle 1 | Vz could not be estimated for Part 1 or Part 2 participants due to insufficient number of samples taken. |
| Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Total HuMax-TF (Conjugated and Non-conjugated) | Before infusion on Day 1, 8 and 15 of Cycle 1 | Data is only available for Part 1, for Part 2, inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3. |
| Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 | — |
| Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Part 1: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 | — |
| Part 2: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 | — |
| Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Free Toxin (MMAE) | Before infusion on Day 1, 8 and 15 of Cycle 1 | Data is only available for Part 1, for Part 2 inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3. |
| Part 1: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result | Baseline to end of follow-up; maximum follow-up was 24 weeks | — |
| Part 1: Number of Participants With Markedly Abnormal Laboratory Values | Baseline to end of follow-up; maximum time of follow-up was 24 weeks | The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Markedly abnormal laboratory values are defined as any grade \>=3 laboratory abnormality events. |
| Part 1: Number of Patients Who Experienced Anti-tumor Activity Measured by Tumor Shrinkage | Baseline to end of trial (Part 1), up to 72 weeks | — |
| Part 2: Anti-tumor Activity Measured by Percentage of Change in Sum of Lesion Measurements | Baseline to end of trial (Part 2), up to 36 weeks | — |
| Part 1: Response Evaluation Based on PSA (Prostate Specific Antigen [Prostate Cancer]): Percentage Change From Baseline to End of Study | Baseline to end of follow-up; maximum follow-up was 24 weeks | — |
| Part 1: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study | Baseline to end of follow-up; maximum follow-up was 24 weeks | — |
| Part 2: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study | Baseline to end of trial (Part 2), up to 36 week | — |
| Part 1: Best Overall Response (OR) | Baseline to end of trial (Part 1), up to 72 weeks | Best OR (by investigators assessment) was the best response recorded from the start of the treatment until disease progression or death. Complete response: the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. Based on non-target lesions, complete response was defined as disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\< 10 mm short axis). Partial response (PR): ≥ 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LDs. Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of LDs while in trial. Based on non-target lesions, stable disease was defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits. |
| Part 2: Best Overall Response (OR) | Baseline to end of trial (Part 2), up to 36 weeks | Best OR (by investigators assessment) was the best response recorded from the start of the treatment until disease progression or death. Complete response: the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. Based on non-target lesions, complete response was defined as disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\< 10 mm short axis). Partial response (PR): ≥ 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LDs. Stable Disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of LDs while in trial. Based on non-target lesions, stable disease was defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits. |
| Part 1: Number of Participants Who Experienced Disease Control | 6, 12, 24 and 36 weeks post first infusion (Part 1) | Participants were defined as having disease control at a specific time point if they had an evaluation of complete response (CR) or partial response (PR) at the time point (with a window of +/- 7 days) or had an evaluation of stable disease (SD), PR or CR at any point from the time point minus 7 days or later. |
| Part 2: Number of Participants Who Experienced Disease Control | 6, 12, 24 and 36 weeks post first infusion (Part 2) | Participants were defined as having disease control at a specific time point if they had an evaluation of complete response (CR) or partial response (PR) at the time point (with a window of +/- 7 days) or had an evaluation of stable disease (SD), PR or CR at any point from the time point minus 7 days or later. |
| Part 1: Progression Free Survival (PFS) | Baseline to end of follow-up; maximum time of follow-up was 24 weeks | Progression-free survival was defined as the time in weeks from date of first dose until the date of disease progression or death, whichever is earliest. |
| Part 2: Progression Free Survival (PFS) | Baseline to end of trial (Part 2), up to 36 weeks | Progression-free survival was defined as the time in weeks from date of first dose until the date of disease progression or death, whichever is earliest. |
| Part 1: Duration of Response | Baseline to end of trial (Part 1), up to 72 weeks | Duration of response was defined as as the number of days from the first documentation of objective tumor response (complete response \[CR\] or partial response \[PR\]) to the date of first progressive disease (PD) or death. |
| Part 2: Duration of Response | Baseline to end of trial (Part 2), up to 36 weeks | Duration of response was defined as as the number of days from the first documentation of objective tumor response (complete response \[CR\] or partial response \[PR\]) to the date of first progressive disease (PD) or death. |
| Part 2: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result | Baseline to end of trial (Part 2), up to 36 weeks | — |
| Part 2: Number of Participants With Markedly Abnormal Laboratory Values | Baseline to end of trial (Part 2), up to 36 weeks | The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Markedly abnormal laboratory values are defined as any grade \>=3 laboratory abnormality events. |
| Part 1: Number of Participants Who Experienced a Skin Rash | Baseline to end of follow-up; maximum time of follow-up was 24 weeks | — |
| Part 2: Number of Participants Who Experienced a Skin Rash | Baseline to end of trial (Part 2), up to 36 weeks | — |
| Part 1: Number of Participants Who Experienced a Bleeding Event | Baseline to end of trial (Part 1), up to 72 weeks | — |
| Part 2: Number of Participants Who Experienced a Bleeding Event | Baseline to end of trial (Part 2), up to 36 weeks | — |
| Part 1: Number of Participants Who Experienced a Neuropathy Event | Baseline to end of follow-up; maximum time of follow-up was 24 weeks | — |
| Part 2: Number of Participants Who Experienced a Neuropathy Event | Baseline to end of trial (Part 2), up to 36 weeks | — |
| Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8 and 15, + 24 hours 1st infusion (Day 2), + 24 hours 3rd infusion (Day 16), + 72 hours 3rd infusion (Day 18), + 168 hours 3rd infusion (Day 22) of Cycle 1 | — |
| Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
Countries
Belgium, Denmark, Hungary, United Kingdom, United States
Participant flow
Recruitment details
For the Dose Escalation, participants took part in the trial at 3 sites located in Denmark, the United Kingdom (UK), and the United States (USA) from 30 Nov 2015 until 10 Feb 2017. Cohort Expansion trial was performed at 10 sites located in Belgium, UK, Denmark, and the USA from 16 Feb 2016 until the last participant visit on 13 Dec 2017.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | 3 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | 6 |
| Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials \[RP2D\] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | 11 |
| Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials \[RP2D\] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | 3 |
| Part 2 Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | 1 |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | 5 |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | 1 |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | 3 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Part 1: Dose Level 1 (Weeks 1-16) | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Dose Level 1 (Weeks 1-16) | Disease Progression | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Dose Level 2 (Week 17-48) | Disease Progression | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Dose Level 2 (Week 17-48) | Investigator Judgment | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Dose Level 2 (Week 17-48) | Miscellaneous | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Dose Level 2 (Week 17-48) | Patient Choice | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2: Cohort Expansion | Adverse Event | 0 | 0 | 6 | 1 | 0 | 0 | 0 | 0 |
| Part 2: Cohort Expansion | Death | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part 2: Cohort Expansion | Disease Progression | 0 | 0 | 3 | 2 | 1 | 4 | 0 | 3 |
| Part 2: Cohort Expansion | Patient Choice | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2 Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized Adults (18-64 years) | 25 Participants | 3 Participants | 10 Participants | 3 Participants | 1 Participants | 0 Participants | 4 Participants | 1 Participants | 3 Participants |
| Age, Customized From 65 to 84 years | 8 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants |
| Body Mass Index (BMI) Part 1: Dose Escalation | 25.7 kg/m^2 | 25.5 kg/m^2 | — | — | — | 27.4 kg/m^2 | — | — | — |
| Body Mass Index (BMI) Part 2: Cohort Expansion | 25.1 kg/m^2 | — | 26.4 kg/m^2 | 22.4 kg/m^2 | 22.4 kg/m^2 | — | 24.0 kg/m^2 | 33.3 kg/m^2 | 24.9 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 6 Participants | 10 Participants | 3 Participants | 1 Participants | 3 Participants | 5 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height Part 1: Dose Escalation | 168.0 cm | 162.0 cm | — | — | — | 171.0 cm | — | — | — |
| Height Part 2: Cohort Expansion | 160.8 cm | — | 159.0 cm | 157.0 cm | 160.6 cm | — | 168.0 cm | 170.5 cm | 161.0 cm |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 31 Participants | 5 Participants | 10 Participants | 3 Participants | 1 Participants | 3 Participants | 5 Participants | 1 Participants | 3 Participants |
| Region of Enrollment Belgium | 13 participants | 0 participants | 6 participants | 3 participants | 0 participants | 0 participants | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Denmark | 5 participants | 2 participants | 0 participants | 0 participants | 0 participants | 2 participants | 1 participants | 0 participants | 0 participants |
| Region of Enrollment United Kingdom | 11 participants | 1 participants | 4 participants | 0 participants | 1 participants | 1 participants | 2 participants | 1 participants | 1 participants |
| Region of Enrollment United States | 4 participants | 3 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 29 Participants | 4 Participants | 11 Participants | 3 Participants | 1 Participants | 1 Participants | 5 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Weight Part 1: Dose Escalation | 74.7 kg | 67.5 kg | — | — | — | 80.0 kg | — | — | — |
| Weight Part 2: Cohort Expansion | 64.8 kg | — | 66.8 kg | 55.2 kg | 57.8 kg | — | 72.0 kg | 96.8 kg | 65.3 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 6 | 1 / 11 | 0 / 3 | 0 / 1 | 0 / 5 | 0 / 1 | 0 / 3 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 10 / 11 | 3 / 3 | 1 / 1 | 5 / 5 | 0 / 1 | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 | 2 / 6 | 9 / 11 | 2 / 3 | 0 / 1 | 2 / 5 | 0 / 1 | 1 / 3 |
Outcome results
Primary
Part 1: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events
A CTCAE AE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator.
Time frame: Baseline to end of follow-up; maximum time of follow-up was 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events | 1 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events | 3 Participants |
Primary
Part 1: Number of Participants Reporting One or More Infusion-related Adverse Events
An infusion-related adverse event (AE) was defined as an AE occurring during infusion where the onset date and time of the event occurred within infusion time (+24 hours), and the event was judged as related to tisotumab vedotin by the investigator.
Time frame: Day 1, Day 8 & Day 15 (+1 day) until end of treatment (Part 1), approximately 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Reporting One or More Infusion-related Adverse Events | 2 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Reporting One or More Infusion-related Adverse Events | 4 Participants |
Primary
Part 1: Number of Participants Reporting One or More Treatment-related Adverse Events
A treatment-related AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; which has a causal relationship with the treatment.
Time frame: Baseline to end of follow-up; maximum time of follow-up was 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Reporting One or More Treatment-related Adverse Events | 3 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Reporting One or More Treatment-related Adverse Events | 6 Participants |
Primary
Part 1: Number of Participants Who Experience at Least One Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Baseline to end of follow-up; maximum time of follow-up was 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Who Experience at Least One Adverse Event (AE) | 3 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Who Experience at Least One Adverse Event (AE) | 6 Participants |
Primary
Part 1: Number of Participants Who Experienced at Least One or More Serious Adverse Event (SAE)
A SAE is defined as an AE that met one or more of the following criteria/outcomes which were classified as serious: Required inpatient hospitalization or prolongation of existing hospitalization. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Was a congenital anomaly/birth defect. Medically important determined by the investigator. Resulted in death. Was life-threatening.
Time frame: Baseline to end of follow-up; maximum time of follow-up was 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Who Experienced at Least One or More Serious Adverse Event (SAE) | 1 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Who Experienced at Least One or More Serious Adverse Event (SAE) | 2 Participants |
Primary
Part 2: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events
A CTCAE AE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator.
Time frame: Baseline to end of trial (Part 2), up to 36 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events | 10 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events | 2 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events | 0 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events | 3 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events | 0 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events | 1 Participants |
Primary
Part 2: Number of Participants Reporting One or More Infusion-related Adverse Events
An infusion-related adverse event (AE) was defined as an AE occurring during infusion where the onset date and time of the event occurred within infusion time (+24 hours), and the event was judged as related to tisotumab vedotin by the investigator.
Time frame: Day 1, Day 8 & Day 15 (+1 day) until end of trial (Part 2), up to 36 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Reporting One or More Infusion-related Adverse Events | 4 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Reporting One or More Infusion-related Adverse Events | 2 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Reporting One or More Infusion-related Adverse Events | 1 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Reporting One or More Infusion-related Adverse Events | 1 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Reporting One or More Infusion-related Adverse Events | 0 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Reporting One or More Infusion-related Adverse Events | 1 Participants |
Primary
Part 2: Number of Participants Reporting One or More Serious Adverse Events (SAE)
A SAE is defined as an AE that met one or more of the following criteria/outcomes which were classified as serious: Required inpatient hospitalization or prolongation of existing hospitalization. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Was a congenital anomaly/birth defect. Medically important determined by the investigator. Resulted in death. Was life-threatening.
Time frame: Baseline to end of trial (Part 2), up to 36 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Reporting One or More Serious Adverse Events (SAE) | 9 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Reporting One or More Serious Adverse Events (SAE) | 2 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Reporting One or More Serious Adverse Events (SAE) | 0 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Reporting One or More Serious Adverse Events (SAE) | 2 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Reporting One or More Serious Adverse Events (SAE) | 0 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Reporting One or More Serious Adverse Events (SAE) | 1 Participants |
Primary
Part 2: Number of Participants Reporting One or More Treatment-related Adverse Events
A treatment-related AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; which has a causal relationship with the treatment.
Time frame: Baseline to end of trial (Part 2), up to 36 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Reporting One or More Treatment-related Adverse Events | 9 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Reporting One or More Treatment-related Adverse Events | 3 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Reporting One or More Treatment-related Adverse Events | 1 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Reporting One or More Treatment-related Adverse Events | 5 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Reporting One or More Treatment-related Adverse Events | 0 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Reporting One or More Treatment-related Adverse Events | 3 Participants |
Primary
Part 2: Number of Participants Who Experience at Least One Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Baseline to end of trial (Part 2), up to 36 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Who Experience at Least One Adverse Event (AE) | 11 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Who Experience at Least One Adverse Event (AE) | 3 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Who Experience at Least One Adverse Event (AE) | 1 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Who Experience at Least One Adverse Event (AE) | 5 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Who Experience at Least One Adverse Event (AE) | 0 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Who Experience at Least One Adverse Event (AE) | 3 Participants |
Secondary
Part 1 and Part 2: Total Clearance (CL) of Total HuMax-TF (Conjugated and Non-conjugated)
CL could not be estimated for Part 1 or Part 2 participants due to insufficient number of samples taken.
Time frame: 0 to 2 hours post-dose on days 1, 8, 15, +24 hrs 1st infusion, +24 hrs 3rd infusion, +72 hrs 3rd infusion, +168 hrs 3rd infusion (Part 1) and 0 to 2 hours post-dose on day 1, and pre-dose days 8 and 15 (Part 2) of Cycle 1
Population: CL could not be estimated for Part 1 or Part 2 participants.
Secondary
Part 1: Apparent Volume of Distribution (Vz) for Tisotumab Vedotin (HuMax-TF-ADC)
Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore Vz could not be determined.
Time frame: Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Includes data for all randomized participants for whom data were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Apparent Volume of Distribution (Vz) for Tisotumab Vedotin (HuMax-TF-ADC) | 66.75 mL/kg | Geometric Coefficient of Variation 6.67 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Apparent Volume of Distribution (Vz) for Tisotumab Vedotin (HuMax-TF-ADC) | 75.37 mL/kg | Geometric Coefficient of Variation 14.89 |
Secondary
Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE)
Time frame: Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 | 885 h*ng/mL | Geometric Coefficient of Variation 27.1 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 Day 1 | 185 h*ng/mL | Geometric Coefficient of Variation 48.1 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 Day 8 | 180 h*ng/mL | Geometric Coefficient of Variation 14.1 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 Day 15 | 506 h*ng/mL | Geometric Coefficient of Variation 25.3 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 Day 15 | 520 h*ng/mL | Geometric Coefficient of Variation 51.3 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 | 968 h*ng/mL | Geometric Coefficient of Variation 59.7 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 Day 8 | 236 h*ng/mL | Geometric Coefficient of Variation 75.5 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 Day 1 | 185 h*ng/mL | Geometric Coefficient of Variation 75.3 |
Secondary
Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC)
Time frame: Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8 and 15, + 24 hours 1st infusion (Day 2), + 24 hours 3rd infusion (Day 16), + 72 hours 3rd infusion (Day 18), + 168 hours 3rd infusion (Day 22) of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 | 3336 h*µg/mL | Geometric Coefficient of Variation 7.3 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 1 | 867 h*µg/mL | Geometric Coefficient of Variation 17.6 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 8 | 1603 h*µg/mL | Geometric Coefficient of Variation 16.2 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 15 | 789 h*µg/mL | Geometric Coefficient of Variation 15.6 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 15 | 1411 h*µg/mL | Geometric Coefficient of Variation 94.2 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 | 5317 h*µg/mL | Geometric Coefficient of Variation 34.6 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 8 | 2216 h*µg/mL | Geometric Coefficient of Variation 11.7 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 1 | 1328 h*µg/mL | Geometric Coefficient of Variation 48 |
Secondary
Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated)
Time frame: Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 | 3916 h*µg/mL | Geometric Coefficient of Variation 7.3 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 1 | 1058 h*µg/mL | Geometric Coefficient of Variation 15 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 8 | 1750 h*µg/mL | Geometric Coefficient of Variation 16.2 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 15 | 1012 h*µg/mL | Geometric Coefficient of Variation 25.7 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 15 | 1426 h*µg/mL | Geometric Coefficient of Variation 28.6 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 | 5573 h*µg/mL | Geometric Coefficient of Variation 15 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 8 | 2460 h*µg/mL | Geometric Coefficient of Variation 8.5 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 1 | 1530 h*µg/mL | Geometric Coefficient of Variation 34.7 |
Secondary
Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Tisotumab Vedotin (HuMax-TF-ADC)
Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase.
Time frame: Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8 and 15, + 24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), +168 hours 3rd infusion (Day 22) of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Includes data for all randomized participants for whom data were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Tisotumab Vedotin (HuMax-TF-ADC) | 920 h*µg/mL | Geometric Coefficient of Variation 3.6 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Tisotumab Vedotin (HuMax-TF-ADC) | 1106 h*µg/mL | Geometric Coefficient of Variation 21.3 |
Secondary
Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Total HuMax-TF (Conjugated and Non-conjugated)
Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase.
Time frame: Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Includes data for all randomized participants for whom data were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Total HuMax-TF (Conjugated and Non-conjugated) | 1268 h*µg/mL | Geometric Coefficient of Variation 14.4 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Total HuMax-TF (Conjugated and Non-conjugated) | 1594 h*µg/mL | Geometric Coefficient of Variation 24.6 |
Secondary
Part 1: Best Overall Response (OR)
Best OR (by investigators assessment) was the best response recorded from the start of the treatment until disease progression or death. Complete response: the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. Based on non-target lesions, complete response was defined as disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\< 10 mm short axis). Partial response (PR): ≥ 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LDs. Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of LDs while in trial. Based on non-target lesions, stable disease was defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.
Time frame: Baseline to end of trial (Part 1), up to 72 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Best Overall Response (OR) | Partial Response | 0 participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Best Overall Response (OR) | Progressive Disease | 1 participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Best Overall Response (OR) | Stable Disease | 2 participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Best Overall Response (OR) | Not Evaluable | 0 participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Best Overall Response (OR) | Complete Response | 0 participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Best Overall Response (OR) | Not Evaluable | 1 participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Best Overall Response (OR) | Complete Response | 0 participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Best Overall Response (OR) | Partial Response | 1 participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Best Overall Response (OR) | Stable Disease | 3 participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Best Overall Response (OR) | Progressive Disease | 1 participants |
Secondary
Part 1: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE)
Time frame: Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 | 2.76 ng/mL | Geometric Coefficient of Variation 23.7 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Day 1 | 1.46 ng/mL | Geometric Coefficient of Variation 54.7 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Day 8 | 1.18 ng/mL | Geometric Coefficient of Variation 19.8 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Day 15 | 2.76 ng/mL | Geometric Coefficient of Variation 23.7 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Day 15 | 2.88 ng/mL | Geometric Coefficient of Variation 52.4 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 | 2.88 ng/mL | Geometric Coefficient of Variation 52.4 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Day 8 | 1.54 ng/mL | Geometric Coefficient of Variation 75.4 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Day 1 | 1.38 ng/mL | Geometric Coefficient of Variation 78.4 |
Secondary
Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)
Time frame: Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 | 21.2 µg/mL | Geometric Coefficient of Variation 14.5 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 1 | 20.2 µg/mL | Geometric Coefficient of Variation 17.9 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 8 | 20.9 µg/mL | Geometric Coefficient of Variation 14.1 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 15 | 19.9 µg/mL | Geometric Coefficient of Variation 11.8 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 15 | 26.8 µg/mL | Geometric Coefficient of Variation 21.6 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 | 30.7 µg/mL | Geometric Coefficient of Variation 10.1 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 8 | 28.0 µg/mL | Geometric Coefficient of Variation 8.9 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 1 | 28.7 µg/mL | Geometric Coefficient of Variation 12.1 |
Secondary
Part 1: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)
Time frame: Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 8 | 21.0 µg/mL | Geometric Coefficient of Variation 6.3 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 | 22.1 µg/mL | Geometric Coefficient of Variation 9.1 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 15 | 20.9 µg/mL | Geometric Coefficient of Variation 12 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 1 | 20.3 µg/mL | Geometric Coefficient of Variation 14.3 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 15 | 29.2 µg/mL | Geometric Coefficient of Variation 16.2 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 | 31.7 µg/mL | Geometric Coefficient of Variation 11.9 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 8 | 29.2 µg/mL | Geometric Coefficient of Variation 6.6 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 1 | 30.2 µg/mL | Geometric Coefficient of Variation 34.7 |
Secondary
Part 1: Duration of Response
Duration of response was defined as as the number of days from the first documentation of objective tumor response (complete response \[CR\] or partial response \[PR\]) to the date of first progressive disease (PD) or death.
Time frame: Baseline to end of trial (Part 1), up to 72 weeks
Population: Duration of Response could not be estimated in the Dose Escalation or the Cohort Expansion parts of the trial because patients with a confirmed response were discontinued due to toxicity or other reason different from progressive disease (PD) or death.
Secondary
Part 1: Number of Participants Who Experienced a Bleeding Event
Time frame: Baseline to end of trial (Part 1), up to 72 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Who Experienced a Bleeding Event | 3 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Who Experienced a Bleeding Event | 5 Participants |
Secondary
Part 1: Number of Participants Who Experienced a Neuropathy Event
Time frame: Baseline to end of follow-up; maximum time of follow-up was 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Who Experienced a Neuropathy Event | 1 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Who Experienced a Neuropathy Event | 3 Participants |
Secondary
Part 1: Number of Participants Who Experienced a Skin Rash
Time frame: Baseline to end of follow-up; maximum time of follow-up was 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Who Experienced a Skin Rash | 0 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Who Experienced a Skin Rash | 4 Participants |
Secondary
Part 1: Number of Participants Who Experienced Disease Control
Participants were defined as having disease control at a specific time point if they had an evaluation of complete response (CR) or partial response (PR) at the time point (with a window of +/- 7 days) or had an evaluation of stable disease (SD), PR or CR at any point from the time point minus 7 days or later.
Time frame: 6, 12, 24 and 36 weeks post first infusion (Part 1)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - No | 3 Participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - Yes | 2 Participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - No | 1 Participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - Yes | 0 Participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - Yes | 0 Participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - No | 3 Participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - Yes | 0 Participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - No | 3 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - No | 6 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - Yes | 0 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - Yes | 3 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - Yes | 0 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - No | 3 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - No | 6 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - Yes | 0 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - No | 6 Participants |
Secondary
Part 1: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result
Time frame: Baseline to end of follow-up; maximum follow-up was 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result | 0 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result | 0 Participants |
Secondary
Part 1: Number of Participants With Markedly Abnormal Laboratory Values
The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Markedly abnormal laboratory values are defined as any grade \>=3 laboratory abnormality events.
Time frame: Baseline to end of follow-up; maximum time of follow-up was 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Participants With Markedly Abnormal Laboratory Values | 0 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Participants With Markedly Abnormal Laboratory Values | 6 Participants |
Secondary
Part 1: Number of Patients Who Experienced Anti-tumor Activity Measured by Tumor Shrinkage
Time frame: Baseline to end of trial (Part 1), up to 72 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Number of Patients Who Experienced Anti-tumor Activity Measured by Tumor Shrinkage | 1 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Number of Patients Who Experienced Anti-tumor Activity Measured by Tumor Shrinkage | 3 Participants |
Secondary
Part 1 & Part 2: Apparent Volume of Distribution (Vz) for Total HuMax-TF (Conjugated and Non-conjugated)
Vz could not be estimated for Part 1 or Part 2 participants due to insufficient number of samples taken.
Time frame: 0 to 2 hours post-dose on days 1, 8, 15, +24 hrs 1st infusion, +24 hrs 3rd infusion, +72 hrs 3rd infusion, +168 hrs 3rd infusion (Part 1) and 0 to 2 hours post-dose on day 1, and pre-dose days 8 and 15 (Part 2) of Cycle 1
Population: Vz could not be estimated for Part 1 or Part 2 participants.
Secondary
Part 1: Progression Free Survival (PFS)
Progression-free survival was defined as the time in weeks from date of first dose until the date of disease progression or death, whichever is earliest.
Time frame: Baseline to end of follow-up; maximum time of follow-up was 24 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Progression Free Survival (PFS) | 11.3 weeks |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Progression Free Survival (PFS) | NA weeks |
Secondary
Part 1: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study
Time frame: Baseline to end of follow-up; maximum follow-up was 24 weeks
Population: CA 125 is only assessed for participants with ovarian and endometrial cancer, 1 participant in Cohort 1 and 1 participant in Cohort 2 had the indication of ovarian or endometrial cancer. No participants from Cohort 1 with the indication of ovarian and endometrial Cancer had results at the End of Study visit.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study | 186.21 percentage of change |
Secondary
Part 1: Response Evaluation Based on PSA (Prostate Specific Antigen [Prostate Cancer]): Percentage Change From Baseline to End of Study
Time frame: Baseline to end of follow-up; maximum follow-up was 24 weeks
Population: PSA is only assessed for participants with prostate cancer. 2 participants in Part 1 Cohort 1 and 1 participant in Part 1 Cohort 2 had the indication of prostate cancer.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Response Evaluation Based on PSA (Prostate Specific Antigen [Prostate Cancer]): Percentage Change From Baseline to End of Study | 23.42 percentage of change | Standard Deviation 61.686 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Response Evaluation Based on PSA (Prostate Specific Antigen [Prostate Cancer]): Percentage Change From Baseline to End of Study | 12.97 percentage of change | — |
Secondary
Part 1: Terminal Phase Elimination Half-life (T1/2) for Tisotumab Vedotin (HuMax-TF-ADC)
Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore t1/2 could not be determined.
Time frame: Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Includes data for all randomized participants for whom data were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Terminal Phase Elimination Half-life (T1/2) for Tisotumab Vedotin (HuMax-TF-ADC) | 40.45 hours | Geometric Coefficient of Variation 24.78 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Terminal Phase Elimination Half-life (T1/2) for Tisotumab Vedotin (HuMax-TF-ADC) | 48.15 hours | Geometric Coefficient of Variation 16.47 |
Secondary
Part 1: Terminal Phase Elimination Half-life (T1/2) for Total HuMax-TF (Conjugated and Non-conjugated)
Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore t1/2 could not be determined.
Time frame: Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Terminal Phase Elimination Half-life (T1/2) for Total HuMax-TF (Conjugated and Non-conjugated) | 49.56 hours | Geometric Coefficient of Variation 17.35 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Terminal Phase Elimination Half-life (T1/2) for Total HuMax-TF (Conjugated and Non-conjugated) | 49.34 hours | Geometric Coefficient of Variation 19.18 |
Secondary
Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE)
Time frame: Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Day 1 | 44.568 hours | Geometric Coefficient of Variation 114.567 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 | 392.024 hours | Geometric Coefficient of Variation 3.256 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Day 8 | 10.354 hours | Geometric Coefficient of Variation 165.509 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Day 15 | 54.511 hours | Geometric Coefficient of Variation 20.424 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Day 15 | 32.537 hours | Geometric Coefficient of Variation 63.879 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Day 8 | 20.837 hours | Geometric Coefficient of Variation 106.094 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 | 373.366 hours | Geometric Coefficient of Variation 6.29 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Day 1 | 32.001 hours | Geometric Coefficient of Variation 125.788 |
Secondary
Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)
Time frame: Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 1 | 0.747 hours | Geometric Coefficient of Variation 11.547 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 | 5.864 hours | Geometric Coefficient of Variation 172.022 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 8 | 0.717 hours | Geometric Coefficient of Variation 0 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 15 | 1.141 hours | Geometric Coefficient of Variation 81.075 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 15 | 1.084 hours | Geometric Coefficient of Variation 73.11 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 1 | 0.873 hours | Geometric Coefficient of Variation 79.228 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 8 | 0.846 hours | Geometric Coefficient of Variation 86.481 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 | 5.061 hours | Geometric Coefficient of Variation 166.177 |
Secondary
Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)
Time frame: Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 | 36.445 hours | Geometric Coefficient of Variation 99.474 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 1 | 0.747 hours | Geometric Coefficient of Variation 11.547 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 8 | 0.717 hours | Geometric Coefficient of Variation 0 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 15 | 0.727 hours | Geometric Coefficient of Variation 4.784 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 15 | 0.896 hours | Geometric Coefficient of Variation 78.665 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 | 14.003 hours | Geometric Coefficient of Variation 117.534 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 8 | 0.869 hours | Geometric Coefficient of Variation 78.568 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 1 | 0.893 hours | Geometric Coefficient of Variation 66.752 |
Secondary
Part 1: Total Clearance (CL) of Tisotumab Vedotin (HuMax-TF-ADC)
Data is only available for Part 1, for Part 2 inadequate pharmacokinetic samples were collected after the third dose to define a terminal phase, and therefore CL could not be determined.
Time frame: Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Includes data for all randomized participants for whom data were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Total Clearance (CL) of Tisotumab Vedotin (HuMax-TF-ADC) | 0.979 mL/h/kg | Geometric Coefficient of Variation 3.561 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Total Clearance (CL) of Tisotumab Vedotin (HuMax-TF-ADC) | 1.085 mL/h/kg | Geometric Coefficient of Variation 21.476 |
Secondary
Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Free Toxin (MMAE)
Data is only available for Part 1, for Part 2 inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3.
Time frame: Before infusion on Day 1, 8 and 15 of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Free Toxin (MMAE) | Cycle 1 Day 1 | 12.50 pg/mL | Geometric Coefficient of Variation 0 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Free Toxin (MMAE) | Cycle 1 Day 8 | 853.42 pg/mL | Geometric Coefficient of Variation 22.93 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Free Toxin (MMAE) | Cycle 1 Day 15 | 1013.22 pg/mL | Geometric Coefficient of Variation 14.47 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Free Toxin (MMAE) | Cycle 1 Day 1 | 12.50 pg/mL | Geometric Coefficient of Variation 0 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Free Toxin (MMAE) | Cycle 1 Day 8 | 1061.28 pg/mL | Geometric Coefficient of Variation 87.81 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Free Toxin (MMAE) | Cycle 1 Day 15 | 1384.29 pg/mL | Geometric Coefficient of Variation 83.43 |
Secondary
Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Tisotumab Vedotin (HuMax-TF-ADC)
Data is only available for Part 1, for Part 2 inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3.
Time frame: Before infusion of Day 1, 8 and 15 of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 1 | 30.0 ng/mL | Geometric Coefficient of Variation 0 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 8 | 797.3 ng/mL | Geometric Coefficient of Variation 22.1 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 15 | 912.1 ng/mL | Geometric Coefficient of Variation 23.7 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 1 | 30.0 ng/mL | Geometric Coefficient of Variation 0 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 8 | 1328.5 ng/mL | Geometric Coefficient of Variation 191.8 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Day 15 | 989.0 ng/mL | Geometric Coefficient of Variation 44.3 |
Secondary
Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Total HuMax-TF (Conjugated and Non-conjugated)
Data is only available for Part 1, for Part 2, inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3.
Time frame: Before infusion on Day 1, 8 and 15 of Cycle 1
Population: Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Data includes all randomized participants for whom data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 1 | 150.0 ng/mL | Geometric Coefficient of Variation 0 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 8 | 1273.1 ng/mL | Geometric Coefficient of Variation 23.4 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 15 | 1625.1 ng/mL | Geometric Coefficient of Variation 24.4 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 1 | 150.0 ng/mL | Geometric Coefficient of Variation 0 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 8 | 1252.2 ng/mL | Geometric Coefficient of Variation 53.3 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Day 15 | 1863.8 ng/mL | Geometric Coefficient of Variation 46.6 |
Secondary
Part 2: Anti-tumor Activity Measured by Percentage of Change in Sum of Lesion Measurements
Time frame: Baseline to end of trial (Part 2), up to 36 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Anti-tumor Activity Measured by Percentage of Change in Sum of Lesion Measurements | -17.34 percentage of change | Standard Deviation 43.388 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Anti-tumor Activity Measured by Percentage of Change in Sum of Lesion Measurements | 32.78 percentage of change | Standard Deviation 83.933 |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Anti-tumor Activity Measured by Percentage of Change in Sum of Lesion Measurements | -63.27 percentage of change | — |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Anti-tumor Activity Measured by Percentage of Change in Sum of Lesion Measurements | 0.74 percentage of change | Standard Deviation 21.877 |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Anti-tumor Activity Measured by Percentage of Change in Sum of Lesion Measurements | 0 percentage of change | — |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Anti-tumor Activity Measured by Percentage of Change in Sum of Lesion Measurements | 11.76 percentage of change | Standard Deviation 27.658 |
Secondary
Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE)
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
Time frame: Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1
Population: Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 | 920 h*ng/mL | Geometric Coefficient of Variation 74.5 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 Dose 1 | 439 h*ng/mL | Geometric Coefficient of Variation 69.3 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 Dose 2 | 378 h*ng/mL | Geometric Coefficient of Variation 121.3 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 Dose 3 | 713 h*ng/mL | Geometric Coefficient of Variation 49.9 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 Dose 3 | 494 h*ng/mL | Geometric Coefficient of Variation 121.7 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 | 1049 h*ng/mL | Geometric Coefficient of Variation 89.4 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 Dose 2 | 366 h*ng/mL | Geometric Coefficient of Variation 77.9 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) | Cycle 1 Dose 1 | 393 h*ng/mL | Geometric Coefficient of Variation 100 |
Secondary
Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC)
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
Time frame: Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1
Population: Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 | 2267 h*µg/mL | Geometric Coefficient of Variation 24.8 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 1 | 1889 h*µg/mL | Geometric Coefficient of Variation 29.3 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 2 | 150 h*µg/mL | Geometric Coefficient of Variation 56.2 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 3 | 410 h*µg/mL | Geometric Coefficient of Variation 26.4 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 3 | 204 h*µg/mL | Geometric Coefficient of Variation 71.3 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 | 1755 h*µg/mL | Geometric Coefficient of Variation 19.1 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 2 | 123 h*µg/mL | Geometric Coefficient of Variation 85.4 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 1 | 1412 h*µg/mL | Geometric Coefficient of Variation 11.9 |
Secondary
Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated)
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
Time frame: Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1
Population: Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 | 2660 h*µg/mL | Geometric Coefficient of Variation 20 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 1 | 1980 h*µg/mL | Geometric Coefficient of Variation 24.5 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 2 | 299 h*µg/mL | Geometric Coefficient of Variation 55 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 3 | 679 h*µg/mL | Geometric Coefficient of Variation 25.7 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 3 | 291 h*µg/mL | Geometric Coefficient of Variation 89.9 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 | 1948 h*µg/mL | Geometric Coefficient of Variation 35.2 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 2 | 192 h*µg/mL | Geometric Coefficient of Variation 80.9 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 1 | 460 h*µg/mL | Geometric Coefficient of Variation 84.5 |
Secondary
Part 2: Best Overall Response (OR)
Best OR (by investigators assessment) was the best response recorded from the start of the treatment until disease progression or death. Complete response: the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. Based on non-target lesions, complete response was defined as disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\< 10 mm short axis). Partial response (PR): ≥ 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LDs. Stable Disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of LDs while in trial. Based on non-target lesions, stable disease was defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.
Time frame: Baseline to end of trial (Part 2), up to 36 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Best Overall Response (OR) | Progressive Disease | 2 participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Best Overall Response (OR) | Partial Response | 3 participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Best Overall Response (OR) | Stable Disease | 3 participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Best Overall Response (OR) | Complete Response | 0 participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Best Overall Response (OR) | Not Evaluable | 3 participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Best Overall Response (OR) | Complete Response | 0 participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Best Overall Response (OR) | Progressive Disease | 2 participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Best Overall Response (OR) | Not Evaluable | 0 participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Best Overall Response (OR) | Partial Response | 1 participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Best Overall Response (OR) | Stable Disease | 0 participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Best Overall Response (OR) | Not Evaluable | 0 participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Best Overall Response (OR) | Progressive Disease | 0 participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Best Overall Response (OR) | Complete Response | 0 participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Best Overall Response (OR) | Stable Disease | 0 participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Best Overall Response (OR) | Partial Response | 1 participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Best Overall Response (OR) | Stable Disease | 2 participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Best Overall Response (OR) | Complete Response | 0 participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Best Overall Response (OR) | Partial Response | 2 participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Best Overall Response (OR) | Progressive Disease | 1 participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Best Overall Response (OR) | Not Evaluable | 0 participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Best Overall Response (OR) | Progressive Disease | 1 participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Best Overall Response (OR) | Complete Response | 0 participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Best Overall Response (OR) | Not Evaluable | 0 participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Best Overall Response (OR) | Partial Response | 0 participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Best Overall Response (OR) | Stable Disease | 0 participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Best Overall Response (OR) | Complete Response | 0 participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Best Overall Response (OR) | Progressive Disease | 1 participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Best Overall Response (OR) | Partial Response | 0 participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Best Overall Response (OR) | Not Evaluable | 0 participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Best Overall Response (OR) | Stable Disease | 2 participants |
Secondary
Part 2: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE)
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
Time frame: Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1
Population: Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 | 3.9 ng/mL | Geometric Coefficient of Variation 97 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Dose 1 | 1.9 ng/mL | Geometric Coefficient of Variation 110.5 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Dose 2 | 2.47 ng/mL | Geometric Coefficient of Variation 136.4 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Dose 3 | 3.78 ng/mL | Geometric Coefficient of Variation 81.6 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Dose 3 | 3.23 ng/mL | Geometric Coefficient of Variation 125 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 | 3.6 ng/mL | Geometric Coefficient of Variation 101.4 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Dose 2 | 2.50 ng/mL | Geometric Coefficient of Variation 81.1 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Dose 1 | 1.5 ng/mL | Geometric Coefficient of Variation 80.4 |
Secondary
Part 2: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
Time frame: Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1
Population: Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 | 28.2 µg/mL | Geometric Coefficient of Variation 34.5 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 1 | 28.2 µg/mL | Geometric Coefficient of Variation 34.5 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 2 | 1.00 µg/mL | Geometric Coefficient of Variation 42 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 3 | 3.85 µg/mL | Geometric Coefficient of Variation 24.5 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 3 | 1.85 µg/mL | Geometric Coefficient of Variation 77.6 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 | 19.5 µg/mL | Geometric Coefficient of Variation 17.6 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 2 | 1.13 µg/mL | Geometric Coefficient of Variation 112.2 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 1 | 19.5 µg/mL | Geometric Coefficient of Variation 17.6 |
Secondary
Part 2: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
Time frame: Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1
Population: Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 | 27.5 µg/mL | Geometric Coefficient of Variation 36.4 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 1 | 27.5 µg/mL | Geometric Coefficient of Variation 36.4 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 2 | 2.00 µg/mL | Geometric Coefficient of Variation 41.6 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 3 | 6.39 µg/mL | Geometric Coefficient of Variation 24.6 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 3 | 3.68 µg/mL | Geometric Coefficient of Variation 66.1 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 | 20.6 µg/mL | Geometric Coefficient of Variation 18.6 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 2 | 1.91 µg/mL | Geometric Coefficient of Variation 105 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 1 | 20.6 µg/mL | Geometric Coefficient of Variation 18.6 |
Secondary
Part 2: Duration of Response
Duration of response was defined as as the number of days from the first documentation of objective tumor response (complete response \[CR\] or partial response \[PR\]) to the date of first progressive disease (PD) or death.
Time frame: Baseline to end of trial (Part 2), up to 36 weeks
Population: Duration of Response could not be estimated in the Dose Escalation or the Cohort Expansion parts of the trial because patients with a confirmed response were discontinued due to toxicity or other reason different from progressive disease (PD) or death.
Secondary
Part 2: Number of Participants Who Experienced a Bleeding Event
Time frame: Baseline to end of trial (Part 2), up to 36 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Who Experienced a Bleeding Event | 7 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Who Experienced a Bleeding Event | 3 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Who Experienced a Bleeding Event | 1 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Who Experienced a Bleeding Event | 5 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Who Experienced a Bleeding Event | 0 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Who Experienced a Bleeding Event | 2 Participants |
Secondary
Part 2: Number of Participants Who Experienced a Neuropathy Event
Time frame: Baseline to end of trial (Part 2), up to 36 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Who Experienced a Neuropathy Event | 3 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Who Experienced a Neuropathy Event | 1 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Who Experienced a Neuropathy Event | 0 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Who Experienced a Neuropathy Event | 2 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Who Experienced a Neuropathy Event | 0 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Who Experienced a Neuropathy Event | 1 Participants |
Secondary
Part 2: Number of Participants Who Experienced a Skin Rash
Time frame: Baseline to end of trial (Part 2), up to 36 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Who Experienced a Skin Rash | 2 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Who Experienced a Skin Rash | 0 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Who Experienced a Skin Rash | 1 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Who Experienced a Skin Rash | 1 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Who Experienced a Skin Rash | 0 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Who Experienced a Skin Rash | 1 Participants |
Secondary
Part 2: Number of Participants Who Experienced Disease Control
Participants were defined as having disease control at a specific time point if they had an evaluation of complete response (CR) or partial response (PR) at the time point (with a window of +/- 7 days) or had an evaluation of stable disease (SD), PR or CR at any point from the time point minus 7 days or later.
Time frame: 6, 12, 24 and 36 weeks post first infusion (Part 2)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - No | 5 Participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - No | 11 Participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - Yes | 6 Participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - Yes | 2 Participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - No | 9 Participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - Yes | 0 Participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - Yes | 0 Participants |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - No | 11 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - No | 2 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - Yes | 1 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - No | 3 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - Yes | 0 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - Yes | 0 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - No | 2 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - Yes | 1 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - No | 3 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - Yes | 1 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - No | 0 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - Yes | 1 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - No | 0 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - Yes | 0 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - No | 1 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - No | 1 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - Yes | 0 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - No | 5 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - No | 3 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - No | 1 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - Yes | 1 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - No | 4 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - Yes | 0 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - Yes | 4 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - Yes | 2 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - No | 1 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - No | 1 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - Yes | 0 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - Yes | 0 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - No | 1 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - Yes | 0 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - Yes | 0 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - No | 1 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - Yes | 2 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - Yes | 0 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - No | 3 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 24 Weeks | Disease Control - No | 3 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - Yes | 1 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 6 Weeks | Disease Control - No | 1 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 36 Weeks | Disease Control - Yes | 0 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants Who Experienced Disease Control | 12 Weeks | Disease Control - No | 2 Participants |
Secondary
Part 2: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result
Time frame: Baseline to end of trial (Part 2), up to 36 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result | 0 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result | 0 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result | 0 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result | 0 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result | 0 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result | 0 Participants |
Secondary
Part 2: Number of Participants With Markedly Abnormal Laboratory Values
The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Markedly abnormal laboratory values are defined as any grade \>=3 laboratory abnormality events.
Time frame: Baseline to end of trial (Part 2), up to 36 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Number of Participants With Markedly Abnormal Laboratory Values | 5 Participants |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Number of Participants With Markedly Abnormal Laboratory Values | 2 Participants |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Number of Participants With Markedly Abnormal Laboratory Values | 0 Participants |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Number of Participants With Markedly Abnormal Laboratory Values | 3 Participants |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Number of Participants With Markedly Abnormal Laboratory Values | 1 Participants |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Number of Participants With Markedly Abnormal Laboratory Values | 3 Participants |
Secondary
Part 2: Progression Free Survival (PFS)
Progression-free survival was defined as the time in weeks from date of first dose until the date of disease progression or death, whichever is earliest.
Time frame: Baseline to end of trial (Part 2), up to 36 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Progression Free Survival (PFS) | 10.7 weeks |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Progression Free Survival (PFS) | 8.0 weeks |
| Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Progression Free Survival (PFS) | 22.0 weeks |
| Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Progression Free Survival (PFS) | 14.0 weeks |
| Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Progression Free Survival (PFS) | 5.0 weeks |
| Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Part 2: Progression Free Survival (PFS) | 11.9 weeks |
Secondary
Part 2: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study
Time frame: Baseline to end of trial (Part 2), up to 36 week
Population: CA 125 was only assessed for participants with Ovarian cancer. No participants from Cohort 5 participated in the End of Trial visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study | -31.75 percentage of change | Standard Deviation 36.235 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study | -32.50 percentage of change | — |
Secondary
Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE)
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
Time frame: Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1
Population: Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 | 307.05 hours | Geometric Coefficient of Variation 36.52 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Dose 1 | 160.56 hours | Geometric Coefficient of Variation 5.66 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Dose 2 | 164.82 hours | Geometric Coefficient of Variation 56.71 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Dose 3 | 78.37 hours | Geometric Coefficient of Variation 50.26 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Dose 3 | 80.37 hours | Geometric Coefficient of Variation 20.24 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 | 410.61 hours | Geometric Coefficient of Variation 3.82 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Dose 2 | 106.93 hours | Geometric Coefficient of Variation 55.38 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) | Cycle 1 Dose 1 | 162.19 hours | Geometric Coefficient of Variation 1.71 |
Secondary
Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
Time frame: Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1
Population: Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 | 0.75 hours | Geometric Coefficient of Variation 68.49 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 1 | 0.75 hours | Geometric Coefficient of Variation 68.49 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 2 | 165.06 hours | Geometric Coefficient of Variation 75.01 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 3 | 71.23 hours | Geometric Coefficient of Variation 24.35 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 3 | 80.37 hours | Geometric Coefficient of Variation 20.24 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 | 0.58 hours | Geometric Coefficient of Variation 22.85 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 2 | 106.93 hours | Geometric Coefficient of Variation 55.38 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) | Cycle 1 Dose 1 | 0.58 hours | Geometric Coefficient of Variation 22.85 |
Secondary
Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
Time frame: Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1
Population: Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 | 0.86 hours | Geometric Coefficient of Variation 73.61 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 1 | 0.86 hours | Geometric Coefficient of Variation 73.61 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 2 | 165.06 hours | Geometric Coefficient of Variation 75.01 |
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 3 | 71.23 hours | Geometric Coefficient of Variation 24.35 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 3 | 80.37 hours | Geometric Coefficient of Variation 20.24 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 | 0.58 hours | Geometric Coefficient of Variation 22.85 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 2 | 106 hours | Geometric Coefficient of Variation 55.38 |
| Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) | Cycle 1 Dose 1 | 0.58 hours | Geometric Coefficient of Variation 22.85 |