Bladder Cancer, Cervix Cancer, Endometrium Cancer, Esophagus Cancer, Lung Cancer(NSCLC), Ovary Cancer, Prostate Cancer (CRPC), Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Conditions
Keywords
ovary cancer, cervix cancer, endometrium cancer, bladder cancer, prostate cancer (CRPC), esophagus cancer, lung cancer(NSCLC), Squamous cell carcinoma of the head and neck (SCCHN)
Brief summary
The purpose of the trial is to establish the tolerability of HuMax-TF-ADC in a mixed population of patients with specified solid tumors.
Detailed description
The study is conducted in two parts. The dose escalation portion of the trial subjects are enrolled into cohorts at increasing dose levels of HuMax-TF-ADC in 21 day treatment cycles. In the Cohort Expansion part of the trial, will further explore the recommended phase 2 dose of 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
Intervention model description
Escalation phase for dose finding followed by expansion phase
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 * Age ≥ 18 years. * Acceptable renal function * Acceptable liver function * Acceptable hematological status (without hematologic support * 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. * Ongoing major 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. * 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 ≥ 100 mg (prednisone or equivalent doses of corticosteroids) within two weeks before the first infusion. * Major surgery within six weeks or open biopsy within 14 days before drug infusion. * Plan for any major surgery during treatment period. * 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. * 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. * Any curable cancer with a complete response (CR) of \> 5 years duration. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Treatment emergent adverse events are reported from Day 1 to 30 days after dosing. The treatment duration ranged from 1 to 249 days in the dose escalation part. | Evaluation of treatment-emergent adverse events (TEAEs) includes number of participants with at least one: TEAE Serious TEAE Infusion-related TEAE Common Terminology Criteria for Adverse Events (CTCAE) grade \>=3 Treatment-related TEAE A CTCAE TEAE was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. |
| Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | Treatment emergent adverse events are reported from Day 1 to 30 days after dosing. The treatment duration ranged from 1 to 325 days in the dose expansion part. | Evaluation of treatment-emergent adverse events (TEAEs) includes number of participants with at least one: TEAE Serious TEAE Infusion-related TEAE Common Terminology Criteria for Adverse Events (CTCAE) grade \>=3 Treatment-related TEAE A CTCAE TEAE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | Day 1 to end of follow-up, up to a maximum of 60 weeks | Number of participants with markedly abnormal biochemistry results were defined as all participants who experienced at least 1 CTCAE grade \>= 3 biochemistry value. A markedly abnormal biochemistry value was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. |
| Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | Day 1 to end of follow-up, up to a maximum of 60 weeks | — |
| Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | Day 1 to end of follow-up, up to a maximum of 60 weeks | Bleeding adverse events of special interest included treatment emergent adverse events with preferred terms within the following standardised MedDRA queries (SMQs): Haemorrhage terms, excluding laboratory terms SMQ \[20000039\] (Broad) and Haemorrhage, laboratory terms SMQ \[20000040\] (Narrow). Bleeding adverse events of special interest were evaluated according to the NCI-CTCAE version 4.03. Bleeding events of all grades are included. Grade 1:Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. |
| Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | Day 1 to end of follow-up, up to a maximum of 60 weeks | Peripheral neuropathy events of special interest were evaluated according to the NCI-CTCAE version 4.03. Peripheral neuropathy events of all grades are included in the numbers below. Grade 1:Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. |
| Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days) | Pharmacokinetic (PK) parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. Data was not collected to report or calculate clearance for the expansion phase. |
| Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days) | PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. Data was not planned to be collected for the volume of distribution of tisotumab vedotin and total HuMax-TF for the dose expansion part. |
| Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days) | PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. |
| Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days) | PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2. AUC0-inf was only analyzed in the dose escalation part of the study. Data was not planned to be collected for the AUC0-inf of tisotumab vedotin and total HuMax-TF for the dose expansion part. |
| Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days) | PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. |
| Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days) | PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. |
| Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days) | PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2. t1/2 was only analyzed for the dose escalation part of the study. Data was not planned to be collected for t1/2 of tisotumab vedotin and total HuMax-TF for the dose expansion part. |
| Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days) | PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. |
| Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | Day 1 to end of follow-up, up to a maximum of 60 weeks | Number of participants with markedly abnormal hematology values was defined as all participants who experienced at least 1 CTCAE grade \>= 3 hematology value. A markedly abnormal hematology value was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. |
| Dose Escalation and Expansion Part: Cmax of Free MMAE | Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days) | PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. |
| Dose Escalation and Expansion Part: Tmax of Free MMAE | Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days) | PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. |
| Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE | Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days) | PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2. T1/2 was determined only for the dose escalation part of the study. |
| Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | Day 1 to end of follow-up, up to a maximum of 60 weeks | Participants who met the criterion for positive ADAs on treatment were defined as participants who were negative at baseline and had at least one positive post-baseline result, or participants who were positive at baseline and had at least one post baseline result with a titer higher than baseline. |
| Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage | Day 1 to end of follow-up, up to a maximum of 60 weeks | Anti-tumor activity measured by the number of participants who experienced tumor shrinkage was not planned to be collected for the dose expansion part. |
| Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction Among Available Post-Baseline Sum of Lesion Measurements | Day 1 to end of follow-up, up to a maximum of 60 weeks | Anti-tumor activity measured by maximum reduction among available post-baseline sum of lesion measurements was not planned to be collected for the dose escalation part. |
| Dose Escalation and Expansion Part: Percentage Change From Baseline in Prostate Specific Antigen (PSA) | Day 1 to end of follow-up, up to a maximum of 60 weeks | PSA was only assessed in participants with castrate-resistant prostate cancer. |
| Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125 | Day 1 to end of follow-up, up to a maximum of 60 weeks | In the dose escalation part, CA-125 was only assessed for participants with ovarian cancer. In the dose expansion part, CA-125 was intended to be assessed only for participants with ovarian and endometrium cancer, but was additionally assessed for some participants with NSCLC and cervical cancer. |
| Dose Escalation and Expansion Part: Objective Response Rate | Day 1 to end of follow-up, up to a maximum of 60 weeks | Objective Response Rate per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Response assessment was investigator based for the escalation part and Independent Review Committee (IRC) based for the expansion part. |
| Dose Escalation and Expansion Part: Disease Control Rate | At 6, 12, 24 and 36 weeks | Disease control rate was defined as the percentage of participants with CR, PR or stable disease (SD) as per investigator assessment per RECIST version 1.1 after 6, 12, 24 and 36 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease. |
| Dose Escalation and Expansion Part: Progression Free Survival (PFS) | Day 1 to end of follow-up, up to a maximum of 60 weeks | PFS was defined as the time in weeks from Day 1 in Cycle 1 to first disease progression or death, whichever occurred earliest, as assessed by the investigator. Only deaths that occurred within 60 days of the last visit were considered in the analysis and result are presented based on Kaplan-Meier estimates. Progression as defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase from nadir in the sum of diameters of target lesions, unequivocal progression in non-target lesions, or the appearance of new lesions |
| Dose Expansion Part: Duration of Response (DOR) | Day 1 to end of follow-up, up to a maximum of 60 weeks | DOR was defined as the median time in weeks from when confirmed response was first documented until the first documented disease progression, or death from any cause, whichever was earliest as assessed by the investigator. A responder was defined as any participant with a best overall response of confirmed CR or PR. |
| Dose Escalation Part: AUC0-inf of Free MMAE | Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days) | PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2. AUC0-inf was not planned to be collected for the dose expansion part. AUC0-inf was not calculated where the percentage of the AUC that was due to the extrapolation was more than 20%. |
| Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | Day 1 to end of follow-up, up to a maximum of 60 weeks | Number of participants with markedly abnormal coagulation values was defined as all participants who experienced at least 1 CTCAE grade \>= 3 coagulation value. A markedly abnormal coagulation value was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. |
Countries
Belgium, Denmark, Sweden, United Kingdom, United States
Participant flow
Pre-assignment details
In the dose escalation part of the study, 40 participants were screened and 27 were enrolled and received treatment. In the dose expansion part of the study, 294 participants were screened and 168 were enrolled and received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation Part: 0.3 mg/kg Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. | 3 |
| Dose Escalation Part: 0.6 mg/kg Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. | 3 |
| Dose Escalation Part: 0.9 mg/kg Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. | 3 |
| Dose Escalation Part: 1.2 mg/kg Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. | 3 |
| Dose Escalation Part: 1.5 mg/kg Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. | 3 |
| Dose Escalation Part: 1.8 mg/kg Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. | 3 |
| Dose Escalation Part: 2.0 mg/kg Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. | 3 |
| Dose Escalation Part: 2.2 mg/kg Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. | 6 |
| Dose Expansion Part: Bladder Cancer Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. | 15 |
| Dose Expansion Part: Cervical Cancer Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. | 55 |
| Dose Expansion Part: Endometrial Cancer Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. | 14 |
| Dose Expansion Part: Esophageal Cancer Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. | 15 |
| Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. | 15 |
| Dose Expansion Part: Ovarian Cancer Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. | 36 |
| Dose Expansion Part: Prostate Cancer Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. | 18 |
| Total | 195 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 3 | 4 | 6 | 4 | 0 | 3 | 5 | 6 |
| Overall Study | Death | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Disease Progression | 2 | 2 | 3 | 2 | 3 | 2 | 3 | 3 | 7 | 40 | 5 | 9 | 9 | 20 | 9 |
| Overall Study | Dose Delay Due to Toxicity | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other - Miscellaneous | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 2 | 3 | 3 | 1 | 2 | 1 |
| Overall Study | Start of New Anti-cancer Treatment | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 3 | 2 | 2 | 1 | 5 | 2 |
Baseline characteristics
| Characteristic | Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) | Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: 0.6 mg/kg | Total | Dose Escalation Part: 0.3 mg/kg | Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: 1.2 mg/kg | Dose Expansion Part: Prostate Cancer | Dose Expansion Part: Esophageal Cancer | Dose Escalation Part: 1.8 mg/kg | Dose Expansion Part: Ovarian Cancer | Dose Expansion Part: Bladder Cancer | Dose Expansion Part: Endometrial Cancer | Dose Expansion Part: Cervical Cancer | Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: 1.5 mg/kg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adults (18-64 years) | 9 Participants | 2 Participants | 1 Participants | 138 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 8 Participants | 2 Participants | 26 Participants | 12 Participants | 8 Participants | 51 Participants | 4 Participants | 2 Participants |
| Age, Customized Children (2-11 years) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized From 65-84 years | 6 Participants | 1 Participants | 2 Participants | 57 Participants | 0 Participants | 0 Participants | 0 Participants | 14 Participants | 7 Participants | 1 Participants | 10 Participants | 3 Participants | 6 Participants | 4 Participants | 2 Participants | 1 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized In utero | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 3 Participants | 3 Participants | 191 Participants | 3 Participants | 3 Participants | 3 Participants | 18 Participants | 15 Participants | 3 Participants | 35 Participants | 15 Participants | 13 Participants | 53 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or Asian American | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 13 Participants | 3 Participants | 3 Participants | 182 Participants | 3 Participants | 3 Participants | 3 Participants | 17 Participants | 13 Participants | 3 Participants | 34 Participants | 15 Participants | 14 Participants | 49 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Female | 12 Participants | 3 Participants | 1 Participants | 140 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants | 3 Participants | 36 Participants | 2 Participants | 14 Participants | 55 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 0 Participants | 2 Participants | 55 Participants | 2 Participants | 2 Participants | 1 Participants | 18 Participants | 12 Participants | 0 Participants | 0 Participants | 13 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
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 | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 1 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 15 | 2 / 55 | 0 / 14 | 1 / 15 | 1 / 15 | 2 / 36 | 1 / 18 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 6 / 6 | 15 / 15 | 55 / 55 | 14 / 14 | 15 / 15 | 15 / 15 | 36 / 36 | 18 / 18 |
| serious Total, serious adverse events | 2 / 3 | 1 / 3 | 0 / 3 | 2 / 3 | 2 / 3 | 2 / 3 | 2 / 3 | 4 / 6 | 7 / 15 | 26 / 55 | 5 / 14 | 8 / 15 | 6 / 15 | 13 / 36 | 6 / 18 |
Outcome results
Primary
Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events
Evaluation of treatment-emergent adverse events (TEAEs) includes number of participants with at least one: TEAE Serious TEAE Infusion-related TEAE Common Terminology Criteria for Adverse Events (CTCAE) grade \>=3 Treatment-related TEAE A CTCAE TEAE was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
Time frame: Treatment emergent adverse events are reported from Day 1 to 30 days after dosing. The treatment duration ranged from 1 to 249 days in the dose escalation part.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs | 3 Participants |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Serious TEAEs | 2 Participants |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Infusion-Related TEAEs | 1 Participants |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | CTCAE Grade >=3 TEAEs | 2 Participants |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs Related to Study Drug | 3 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Serious TEAEs | 1 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Infusion-Related TEAEs | 0 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | CTCAE Grade >=3 TEAEs | 3 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs | 3 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs Related to Study Drug | 3 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Infusion-Related TEAEs | 0 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Serious TEAEs | 0 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs Related to Study Drug | 2 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | CTCAE Grade >=3 TEAEs | 1 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs | 3 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Serious TEAEs | 2 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs | 3 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs Related to Study Drug | 3 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Infusion-Related TEAEs | 0 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | CTCAE Grade >=3 TEAEs | 1 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs Related to Study Drug | 3 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Serious TEAEs | 2 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | CTCAE Grade >=3 TEAEs | 2 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Infusion-Related TEAEs | 0 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs | 3 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs | 3 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | CTCAE Grade >=3 TEAEs | 3 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Infusion-Related TEAEs | 0 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs Related to Study Drug | 3 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Serious TEAEs | 2 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | CTCAE Grade >=3 TEAEs | 2 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs Related to Study Drug | 3 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Infusion-Related TEAEs | 0 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Serious TEAEs | 2 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs | 3 Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Serious TEAEs | 4 Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | Infusion-Related TEAEs | 0 Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | CTCAE Grade >=3 TEAEs | 4 Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs Related to Study Drug | 6 Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs | 6 Participants |
Primary
Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events
Evaluation of treatment-emergent adverse events (TEAEs) includes number of participants with at least one: TEAE Serious TEAE Infusion-related TEAE Common Terminology Criteria for Adverse Events (CTCAE) grade \>=3 Treatment-related TEAE A CTCAE TEAE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
Time frame: Treatment emergent adverse events are reported from Day 1 to 30 days after dosing. The treatment duration ranged from 1 to 325 days in the dose expansion part.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | Infusion-Related TEAEs | 1 Participants |
| Dose Escalation Part: 0.3 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs | 15 Participants |
| Dose Escalation Part: 0.3 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | CTCAE Grade >=3 TEAEs | 9 Participants |
| Dose Escalation Part: 0.3 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | Serious TEAEs | 7 Participants |
| Dose Escalation Part: 0.3 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs Related to Study Drug | 15 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | Infusion-Related TEAEs | 1 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | Serious TEAEs | 26 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs | 55 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs Related to Study Drug | 54 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | CTCAE Grade >=3 TEAEs | 30 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs Related to Study Drug | 13 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | Serious TEAEs | 5 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs | 14 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | Infusion-Related TEAEs | 1 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | CTCAE Grade >=3 TEAEs | 8 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs Related to Study Drug | 14 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs | 15 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | Serious TEAEs | 8 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | Infusion-Related TEAEs | 1 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | CTCAE Grade >=3 TEAEs | 8 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs Related to Study Drug | 14 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | Serious TEAEs | 6 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs | 15 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | CTCAE Grade >=3 TEAEs | 10 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | Infusion-Related TEAEs | 2 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | Infusion-Related TEAEs | 0 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | CTCAE Grade >=3 TEAEs | 16 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | Serious TEAEs | 13 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs Related to Study Drug | 36 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs | 36 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | Infusion-Related TEAEs | 0 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs Related to Study Drug | 18 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | TEAEs | 18 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | Serious TEAEs | 6 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events | CTCAE Grade >=3 TEAEs | 11 Participants |
Secondary
Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF
PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
Time frame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
Population: PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 2.0 day*ug/mL | Geometric Coefficient of Variation 15.7 |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 2.4 day*ug/mL | Geometric Coefficient of Variation 12.3 |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 2.5 day*ug/mL | Geometric Coefficient of Variation 3.1 |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 2.9 day*ug/mL | Geometric Coefficient of Variation 0.5 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 14.4 day*ug/mL | Geometric Coefficient of Variation 55.4 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 15.4 day*ug/mL | Geometric Coefficient of Variation 8.2 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 9.9 day*ug/mL | Geometric Coefficient of Variation 49.1 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 15.4 day*ug/mL | Geometric Coefficient of Variation 53.1 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 25.1 day*ug/mL | Geometric Coefficient of Variation 16.9 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 35.7 day*ug/mL | Geometric Coefficient of Variation 7.1 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 35.0 day*ug/mL | Geometric Coefficient of Variation 18.9 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 25.6 day*ug/mL | Geometric Coefficient of Variation 7.1 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 45.2 day*ug/mL | Geometric Coefficient of Variation 9.3 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 45.2 day*ug/mL | Geometric Coefficient of Variation 10.1 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 58.8 day*ug/mL | Geometric Coefficient of Variation 15.5 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 60.4 day*ug/mL | Geometric Coefficient of Variation 13.4 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 40.9 day*ug/mL | Geometric Coefficient of Variation 26.2 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 33.1 day*ug/mL | Geometric Coefficient of Variation 19 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 44.9 day*ug/mL | Geometric Coefficient of Variation 27.8 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 29.8 day*ug/mL | Geometric Coefficient of Variation 25.1 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 63.0 day*ug/mL | Geometric Coefficient of Variation 49.3 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 60.2 day*ug/mL | Geometric Coefficient of Variation 76.6 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 86.7 day*ug/mL | Geometric Coefficient of Variation 54.3 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 42.7 day*ug/mL | Geometric Coefficient of Variation 72.7 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 85.9 day*ug/mL | Geometric Coefficient of Variation 36.7 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 52.3 day*ug/mL | Geometric Coefficient of Variation 33.1 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 92.5 day*ug/mL | Geometric Coefficient of Variation 33.4 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 62.7 day*ug/mL | Geometric Coefficient of Variation 21.5 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 84.9 day*ug/mL | Geometric Coefficient of Variation 33.7 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 86.3 day*ug/mL | Geometric Coefficient of Variation 14.4 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 123.0 day*ug/mL | Geometric Coefficient of Variation 34.7 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 133.6 day*ug/mL | Geometric Coefficient of Variation 13.9 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 112.70 day*ug/mL | Geometric Coefficient of Variation 45.23 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 68.54 day*ug/mL | Geometric Coefficient of Variation 55.49 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 114.54 day*ug/mL | Geometric Coefficient of Variation 45.83 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 79.31 day*ug/mL | Geometric Coefficient of Variation 49.4 |
Secondary
Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE)
PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
Time frame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
Population: PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 1 | 6.20 day*ng/mL | Geometric Coefficient of Variation 72.05 |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 2 | 3.19 day*ng/mL | Geometric Coefficient of Variation 140.85 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 1 | 12.61 day*ng/mL | Geometric Coefficient of Variation 28.18 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 2 | 4.69 day*ng/mL | Geometric Coefficient of Variation 87.27 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 1 | 12.22 day*ng/mL | Geometric Coefficient of Variation 67.23 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 2 | 14.89 day*ng/mL | Geometric Coefficient of Variation 66.97 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 1 | 11.63 day*ng/mL | Geometric Coefficient of Variation 52.69 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 2 | 16.92 day*ng/mL | Geometric Coefficient of Variation 58.12 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 1 | 26.55 day*ng/mL | Geometric Coefficient of Variation 44.24 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 2 | 21.51 day*ng/mL | Geometric Coefficient of Variation 34.25 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 2 | 18.97 day*ng/mL | Geometric Coefficient of Variation 52.14 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 1 | 22.55 day*ng/mL | Geometric Coefficient of Variation 57.26 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 2 | 36.20 day*ng/mL | Geometric Coefficient of Variation 33.82 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 1 | 67.42 day*ng/mL | Geometric Coefficient of Variation 59.98 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 1 | 26.47 day*ng/mL | Geometric Coefficient of Variation 59.35 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 2 | 37.50 day*ng/mL | Geometric Coefficient of Variation 43.08 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 1 | 25.80 day*ng/mL | Geometric Coefficient of Variation 93.91 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) | Cycle 2 | 23.48 day*ng/mL | Geometric Coefficient of Variation 76.47 |
Secondary
Dose Escalation and Expansion Part: Cmax of Free MMAE
PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
Time frame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
Population: PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 1 | 0.760 ng/mL | Geometric Coefficient of Variation 62.505 |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 2 | 1.091 ng/mL | Geometric Coefficient of Variation 74.293 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 1 | 1.673 ng/mL | Geometric Coefficient of Variation 30.756 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 2 | 1.342 ng/mL | Geometric Coefficient of Variation 24.32 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 1 | 1.524 ng/mL | Geometric Coefficient of Variation 54.491 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 2 | 2.059 ng/mL | Geometric Coefficient of Variation 51.47 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 1 | 1.410 ng/mL | Geometric Coefficient of Variation 19.149 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 2 | 2.243 ng/mL | Geometric Coefficient of Variation 50.367 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 1 | 2.807 ng/mL | Geometric Coefficient of Variation 39.398 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 2 | 2.718 ng/mL | Geometric Coefficient of Variation 39.492 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 2 | 2.035 ng/mL | Geometric Coefficient of Variation 39.785 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 1 | 2.587 ng/mL | Geometric Coefficient of Variation 29.172 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 2 | 3.369 ng/mL | Geometric Coefficient of Variation 36.875 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 1 | 6.351 ng/mL | Geometric Coefficient of Variation 61.505 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 1 | 4.877 ng/mL | Geometric Coefficient of Variation 31.35 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 2 | 4.704 ng/mL | Geometric Coefficient of Variation 18.856 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 1 | 3.16 ng/mL | Geometric Coefficient of Variation 88.3 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Cmax of Free MMAE | Cycle 2 | 2.73 ng/mL | Geometric Coefficient of Variation 78.69 |
Secondary
Dose Escalation and Expansion Part: Disease Control Rate
Disease control rate was defined as the percentage of participants with CR, PR or stable disease (SD) as per investigator assessment per RECIST version 1.1 after 6, 12, 24 and 36 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease.
Time frame: At 6, 12, 24 and 36 weeks
Population: Full analysis set: all participants who had been exposed to tisotumab vedotin in either the dose escalation or expansion parts.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 6 | 0 Percentage of Participants |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 24 | 0 Percentage of Participants |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 12 | 0 Percentage of Participants |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 36 | 0 Percentage of Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 6 | 33 Percentage of Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 12 | 33 Percentage of Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 36 | 33 Percentage of Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 24 | 33 Percentage of Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 12 | 33 Percentage of Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 6 | 33 Percentage of Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 36 | 0 Percentage of Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 24 | 0 Percentage of Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 6 | 67 Percentage of Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 12 | 67 Percentage of Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 24 | 33 Percentage of Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 36 | 33 Percentage of Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 12 | 0 Percentage of Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 36 | 0 Percentage of Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 24 | 0 Percentage of Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 6 | 33 Percentage of Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 12 | 67 Percentage of Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 24 | 0 Percentage of Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 36 | 0 Percentage of Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 6 | 100 Percentage of Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 12 | 33 Percentage of Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 6 | 67 Percentage of Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 24 | 0 Percentage of Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 36 | 0 Percentage of Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 12 | 0 Percentage of Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 36 | 0 Percentage of Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 6 | 50 Percentage of Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Disease Control Rate | Week 24 | 0 Percentage of Participants |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 6 | 47 Percentage of Participants |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 24 | 20 Percentage of Participants |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 12 | 33 Percentage of Participants |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 36 | 7 Percentage of Participants |
| Dose Expansion Part: Cervical Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 12 | 47 Percentage of Participants |
| Dose Expansion Part: Cervical Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 24 | 18 Percentage of Participants |
| Dose Expansion Part: Cervical Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 6 | 60 Percentage of Participants |
| Dose Expansion Part: Cervical Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 36 | 11 Percentage of Participants |
| Dose Expansion Part: Endometrial Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 24 | 21 Percentage of Participants |
| Dose Expansion Part: Endometrial Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 36 | 0 Percentage of Participants |
| Dose Expansion Part: Endometrial Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 12 | 43 Percentage of Participants |
| Dose Expansion Part: Endometrial Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 6 | 64 Percentage of Participants |
| Dose Expansion Part: Esophageal Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 36 | 0 Percentage of Participants |
| Dose Expansion Part: Esophageal Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 6 | 40 Percentage of Participants |
| Dose Expansion Part: Esophageal Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 12 | 20 Percentage of Participants |
| Dose Expansion Part: Esophageal Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 24 | 7 Percentage of Participants |
| Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) | Dose Escalation and Expansion Part: Disease Control Rate | Week 6 | 60 Percentage of Participants |
| Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) | Dose Escalation and Expansion Part: Disease Control Rate | Week 12 | 13 Percentage of Participants |
| Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) | Dose Escalation and Expansion Part: Disease Control Rate | Week 36 | 7 Percentage of Participants |
| Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) | Dose Escalation and Expansion Part: Disease Control Rate | Week 24 | 13 Percentage of Participants |
| Dose Expansion Part: Ovarian Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 6 | 72 Percentage of Participants |
| Dose Expansion Part: Ovarian Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 12 | 42 Percentage of Participants |
| Dose Expansion Part: Ovarian Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 24 | 14 Percentage of Participants |
| Dose Expansion Part: Ovarian Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 36 | 3 Percentage of Participants |
| Dose Expansion Part: Prostate Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 6 | 61 Percentage of Participants |
| Dose Expansion Part: Prostate Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 12 | 28 Percentage of Participants |
| Dose Expansion Part: Prostate Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 36 | 6 Percentage of Participants |
| Dose Expansion Part: Prostate Cancer | Dose Escalation and Expansion Part: Disease Control Rate | Week 24 | 6 Percentage of Participants |
Secondary
Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF
PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
Time frame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
Population: PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 3.96 ug/mL | Geometric Coefficient of Variation 21.83 |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 4.78 ug/mL | Geometric Coefficient of Variation 12.35 |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 3.85 ug/mL | Geometric Coefficient of Variation 27.65 |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 4.90 ug/mL | Geometric Coefficient of Variation 13 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 11.84 ug/mL | Geometric Coefficient of Variation 8.31 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 12.20 ug/mL | Geometric Coefficient of Variation 9.47 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 11.54 ug/mL | Geometric Coefficient of Variation 8.83 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 12.51 ug/mL | Geometric Coefficient of Variation 11.51 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 16.90 ug/mL | Geometric Coefficient of Variation 1.57 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 19.81 ug/mL | Geometric Coefficient of Variation 17.32 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 20.25 ug/mL | Geometric Coefficient of Variation 5.14 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 17.98 ug/mL | Geometric Coefficient of Variation 11.64 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 34.67 ug/mL | Geometric Coefficient of Variation 18.48 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 29.30 ug/mL | Geometric Coefficient of Variation 10.14 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 31.33 ug/mL | Geometric Coefficient of Variation 8.13 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 32.38 ug/mL | Geometric Coefficient of Variation 7.11 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 22.11 ug/mL | Geometric Coefficient of Variation 21.03 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 21.84 ug/mL | Geometric Coefficient of Variation 24.97 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 23.55 ug/mL | Geometric Coefficient of Variation 25.16 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 23.12 ug/mL | Geometric Coefficient of Variation 21.1 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 35.92 ug/mL | Geometric Coefficient of Variation 30.39 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 37.71 ug/mL | Geometric Coefficient of Variation 42.96 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 35.42 ug/mL | Geometric Coefficient of Variation 39.2 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 30.57 ug/mL | Geometric Coefficient of Variation 37.42 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 44.30 ug/mL | Geometric Coefficient of Variation 0.32 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 32.30 ug/mL | Geometric Coefficient of Variation 22.08 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 43.40 ug/mL | Geometric Coefficient of Variation 6.67 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 38.78 ug/mL | Geometric Coefficient of Variation 21.77 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 58.02 ug/mL | Geometric Coefficient of Variation 12.77 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 55.53 ug/mL | Geometric Coefficient of Variation 10.31 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 48.79 ug/mL | Geometric Coefficient of Variation 26.37 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 53.67 ug/mL | Geometric Coefficient of Variation 19.75 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 38.3 ug/mL | Geometric Coefficient of Variation 33.3 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 39.8 ug/mL | Geometric Coefficient of Variation 31.1 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 29.1 ug/mL | Geometric Coefficient of Variation 34.1 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 26.1 ug/mL | Geometric Coefficient of Variation 41.2 |
Secondary
Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event
Peripheral neuropathy events of special interest were evaluated according to the NCI-CTCAE version 4.03. Peripheral neuropathy events of all grades are included in the numbers below. Grade 1:Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | 0 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | 1 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | 1 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | 1 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | 0 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | 1 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | 0 Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | 1 Participants |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | 5 Participants |
| Dose Expansion Part: Cervical Cancer | Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | 17 Participants |
| Dose Expansion Part: Endometrial Cancer | Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | 6 Participants |
| Dose Expansion Part: Esophageal Cancer | Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | 3 Participants |
| Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) | Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | 5 Participants |
| Dose Expansion Part: Ovarian Cancer | Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | 17 Participants |
| Dose Expansion Part: Prostate Cancer | Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event | 7 Participants |
Secondary
Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values
Number of participants with markedly abnormal biochemistry results were defined as all participants who experienced at least 1 CTCAE grade \>= 3 biochemistry value. A markedly abnormal biochemistry value was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | 2 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | 1 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | 3 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | 0 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | 1 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | 0 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | 1 Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | 2 Participants |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | 4 Participants |
| Dose Expansion Part: Cervical Cancer | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | 8 Participants |
| Dose Expansion Part: Endometrial Cancer | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | 4 Participants |
| Dose Expansion Part: Esophageal Cancer | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | 6 Participants |
| Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | 2 Participants |
| Dose Expansion Part: Ovarian Cancer | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | 9 Participants |
| Dose Expansion Part: Prostate Cancer | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values | 4 Participants |
Secondary
Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values
Number of participants with markedly abnormal hematology values was defined as all participants who experienced at least 1 CTCAE grade \>= 3 hematology value. A markedly abnormal hematology value was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | 2 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | 1 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | 1 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | 0 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | 2 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | 2 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | 0 Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | 1 Participants |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | 0 Participants |
| Dose Expansion Part: Cervical Cancer | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | 23 Participants |
| Dose Expansion Part: Endometrial Cancer | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | 0 Participants |
| Dose Expansion Part: Esophageal Cancer | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | 3 Participants |
| Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | 1 Participants |
| Dose Expansion Part: Ovarian Cancer | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | 5 Participants |
| Dose Expansion Part: Prostate Cancer | Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values | 3 Participants |
Secondary
Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin
Participants who met the criterion for positive ADAs on treatment were defined as participants who were negative at baseline and had at least one positive post-baseline result, or participants who were positive at baseline and had at least one post baseline result with a titer higher than baseline.
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Population: Full analysis set: all participants who had been exposed to tisotumab vedotin in either the dose escalation or expansion parts.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | 0 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | 0 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | 0 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | 0 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | 0 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | 0 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | 0 Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | 0 Participants |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | 1 Participants |
| Dose Expansion Part: Cervical Cancer | Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | 3 Participants |
| Dose Expansion Part: Endometrial Cancer | Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | 0 Participants |
| Dose Expansion Part: Esophageal Cancer | Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | 0 Participants |
| Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) | Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | 1 Participants |
| Dose Expansion Part: Ovarian Cancer | Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | 0 Participants |
| Dose Expansion Part: Prostate Cancer | Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin | 1 Participants |
Secondary
Dose Escalation and Expansion Part: Objective Response Rate
Objective Response Rate per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Response assessment was investigator based for the escalation part and Independent Review Committee (IRC) based for the expansion part.
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Population: Full analysis set: all participants who had been exposed to tisotumab vedotin in either the dose escalation or expansion parts.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Objective Response Rate | 0 Percentage of Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Objective Response Rate | 0 Percentage of Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Objective Response Rate | 0 Percentage of Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Objective Response Rate | 33 Percentage of Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Objective Response Rate | 0 Percentage of Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Objective Response Rate | 0 Percentage of Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Objective Response Rate | 0 Percentage of Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Objective Response Rate | 0 Percentage of Participants |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Objective Response Rate | 27 Percentage of Participants |
| Dose Expansion Part: Cervical Cancer | Dose Escalation and Expansion Part: Objective Response Rate | 24 Percentage of Participants |
| Dose Expansion Part: Endometrial Cancer | Dose Escalation and Expansion Part: Objective Response Rate | 7 Percentage of Participants |
| Dose Expansion Part: Esophageal Cancer | Dose Escalation and Expansion Part: Objective Response Rate | 13 Percentage of Participants |
| Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) | Dose Escalation and Expansion Part: Objective Response Rate | 13 Percentage of Participants |
| Dose Expansion Part: Ovarian Cancer | Dose Escalation and Expansion Part: Objective Response Rate | 14 Percentage of Participants |
| Dose Expansion Part: Prostate Cancer | Dose Escalation and Expansion Part: Objective Response Rate | 0 Percentage of Participants |
Secondary
Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125
In the dose escalation part, CA-125 was only assessed for participants with ovarian cancer. In the dose expansion part, CA-125 was intended to be assessed only for participants with ovarian and endometrium cancer, but was additionally assessed for some participants with NSCLC and cervical cancer.
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Population: Analyses includes all participants in the dose escalation and expansion parts with ovarian cancer and some participants with NSCLC and cervical cancer in the dose expansion part who have a baseline and end of study evaluable assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125 | 18.75 Percentage Change |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125 | -13.98 Percentage Change |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125 | 113.71 Percentage Change |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125 | 11.62 Percentage Change |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125 | -25.17 Percentage Change |
| Dose Expansion Part: Cervical Cancer | Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125 | 37.85 Percentage Change |
| Dose Expansion Part: Endometrial Cancer | Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125 | 180.94 Percentage Change |
| Dose Expansion Part: Esophageal Cancer | Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125 | 73.19 Percentage Change |
Secondary
Dose Escalation and Expansion Part: Percentage Change From Baseline in Prostate Specific Antigen (PSA)
PSA was only assessed in participants with castrate-resistant prostate cancer.
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Population: Analyses includes all participants with castrate-resistant prostate cancer who have a baseline and end of study evaluable assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Percentage Change From Baseline in Prostate Specific Antigen (PSA) | 64.35 Percentage Change in PSA |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Percentage Change From Baseline in Prostate Specific Antigen (PSA) | 40.91 Percentage Change in PSA |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Percentage Change From Baseline in Prostate Specific Antigen (PSA) | 3.92 Percentage Change in PSA |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Percentage Change From Baseline in Prostate Specific Antigen (PSA) | 60.07 Percentage Change in PSA |
Secondary
Dose Escalation and Expansion Part: Progression Free Survival (PFS)
PFS was defined as the time in weeks from Day 1 in Cycle 1 to first disease progression or death, whichever occurred earliest, as assessed by the investigator. Only deaths that occurred within 60 days of the last visit were considered in the analysis and result are presented based on Kaplan-Meier estimates. Progression as defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase from nadir in the sum of diameters of target lesions, unequivocal progression in non-target lesions, or the appearance of new lesions
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Population: Participants with documented disease progression and/or death are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Progression Free Survival (PFS) | 5.1 Weeks |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Progression Free Survival (PFS) | 6.0 Weeks |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Progression Free Survival (PFS) | 6.1 Weeks |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Progression Free Survival (PFS) | 27.1 Weeks |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Progression Free Survival (PFS) | 6.1 Weeks |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Progression Free Survival (PFS) | 17.1 Weeks |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Progression Free Survival (PFS) | 12.3 Weeks |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Progression Free Survival (PFS) | 11.3 Weeks |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Progression Free Survival (PFS) | 11.0 Weeks |
| Dose Expansion Part: Cervical Cancer | Dose Escalation and Expansion Part: Progression Free Survival (PFS) | 18.1 Weeks |
| Dose Expansion Part: Endometrial Cancer | Dose Escalation and Expansion Part: Progression Free Survival (PFS) | NA Weeks |
| Dose Expansion Part: Esophageal Cancer | Dose Escalation and Expansion Part: Progression Free Survival (PFS) | 10.1 Weeks |
| Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) | Dose Escalation and Expansion Part: Progression Free Survival (PFS) | 13.0 Weeks |
| Dose Expansion Part: Ovarian Cancer | Dose Escalation and Expansion Part: Progression Free Survival (PFS) | 13.0 Weeks |
| Dose Expansion Part: Prostate Cancer | Dose Escalation and Expansion Part: Progression Free Survival (PFS) | 12.9 Weeks |
Secondary
Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest
Bleeding adverse events of special interest included treatment emergent adverse events with preferred terms within the following standardised MedDRA queries (SMQs): Haemorrhage terms, excluding laboratory terms SMQ \[20000039\] (Broad) and Haemorrhage, laboratory terms SMQ \[20000040\] (Narrow). Bleeding adverse events of special interest were evaluated according to the NCI-CTCAE version 4.03. Bleeding events of all grades are included. Grade 1:Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | 0 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | 1 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | 0 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | 3 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | 3 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | 3 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | 2 Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | 5 Participants |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | 10 Participants |
| Dose Expansion Part: Cervical Cancer | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | 31 Participants |
| Dose Expansion Part: Endometrial Cancer | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | 10 Participants |
| Dose Expansion Part: Esophageal Cancer | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | 7 Participants |
| Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | 9 Participants |
| Dose Expansion Part: Ovarian Cancer | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | 27 Participants |
| Dose Expansion Part: Prostate Cancer | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest | 10 Participants |
Secondary
Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | 1 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | 0 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | 0 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | 2 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | 0 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | 2 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | 2 Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | 4 Participants |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | 3 Participants |
| Dose Expansion Part: Cervical Cancer | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | 6 Participants |
| Dose Expansion Part: Endometrial Cancer | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | 2 Participants |
| Dose Expansion Part: Esophageal Cancer | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | 2 Participants |
| Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | 2 Participants |
| Dose Expansion Part: Ovarian Cancer | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | 8 Participants |
| Dose Expansion Part: Prostate Cancer | Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash | 5 Participants |
Secondary
Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values
Number of participants with markedly abnormal coagulation values was defined as all participants who experienced at least 1 CTCAE grade \>= 3 coagulation value. A markedly abnormal coagulation value was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | 0 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | 0 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | 0 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | 0 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | 0 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | 0 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | 0 Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | 1 Participants |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | 1 Participants |
| Dose Expansion Part: Cervical Cancer | Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | 7 Participants |
| Dose Expansion Part: Endometrial Cancer | Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | 2 Participants |
| Dose Expansion Part: Esophageal Cancer | Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | 0 Participants |
| Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) | Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | 2 Participants |
| Dose Expansion Part: Ovarian Cancer | Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | 5 Participants |
| Dose Expansion Part: Prostate Cancer | Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values | 4 Participants |
Secondary
Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF
PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
Time frame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
Population: PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 1.47 hours | Geometric Coefficient of Variation 72.74 |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 2.19 hours | Geometric Coefficient of Variation 46.56 |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 1.54 hours | Geometric Coefficient of Variation 63.29 |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 2.20 hours | Geometric Coefficient of Variation 49.15 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 1.34 hours | Geometric Coefficient of Variation 6.27 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 1.18 hours | Geometric Coefficient of Variation 13.03 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 1.34 hours | Geometric Coefficient of Variation 6.27 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 1.18 hours | Geometric Coefficient of Variation 13.03 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 1.32 hours | Geometric Coefficient of Variation 5.96 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 1.34 hours | Geometric Coefficient of Variation 11.77 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 1.32 hours | Geometric Coefficient of Variation 5.96 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 1.34 hours | Geometric Coefficient of Variation 11.77 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 1.15 hours | Geometric Coefficient of Variation 11.66 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 1.13 hours | Geometric Coefficient of Variation 11.18 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 1.15 hours | Geometric Coefficient of Variation 11.66 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 1.13 hours | Geometric Coefficient of Variation 11.18 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 1.12 hours | Geometric Coefficient of Variation 9.55 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 1.12 hours | Geometric Coefficient of Variation 9.55 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 1.21 hours | Geometric Coefficient of Variation 16.61 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 1.21 hours | Geometric Coefficient of Variation 16.61 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 2.44 hours | Geometric Coefficient of Variation 35.75 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 1.18 hours | Geometric Coefficient of Variation 14.3 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 1.76 hours | Geometric Coefficient of Variation 50.43 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 1.18 hours | Geometric Coefficient of Variation 14.3 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 1.14 hours | Geometric Coefficient of Variation 9.29 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 1.18 hours | Geometric Coefficient of Variation 7.45 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 1.18 hours | Geometric Coefficient of Variation 7.45 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 1.14 hours | Geometric Coefficient of Variation 9.29 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 1.11 hours | Geometric Coefficient of Variation 12.52 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 1.11 hours | Geometric Coefficient of Variation 12.52 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 1.29 hours | Geometric Coefficient of Variation 7.55 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 1.29 hours | Geometric Coefficient of Variation 7.55 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 1.15 hours | Geometric Coefficient of Variation 356.23 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 1.21 hours | Geometric Coefficient of Variation 364.12 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 1.10 hours | Geometric Coefficient of Variation 397.92 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 1.44 hours | Geometric Coefficient of Variation 303.89 |
Secondary
Dose Escalation and Expansion Part: Tmax of Free MMAE
PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
Time frame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
Population: PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 1 | 23.88 hours | Geometric Coefficient of Variation 4.41 |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 2 | 23.73 hours | Geometric Coefficient of Variation 5.78 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 1 | 22.77 hours | Geometric Coefficient of Variation 16.56 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 2 | 24.05 hours | Geometric Coefficient of Variation 8.48 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 1 | 24.39 hours | Geometric Coefficient of Variation 7.72 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 2 | 23.92 hours | Geometric Coefficient of Variation 13.04 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 1 | 24.19 hours | Geometric Coefficient of Variation 5.52 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 2 | 24.94 hours | Geometric Coefficient of Variation 1.48 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 1 | 25.07 hours | Geometric Coefficient of Variation 0.68 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 2 | 25.26 hours | Geometric Coefficient of Variation 0.76 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 2 | 46.24 hours | Geometric Coefficient of Variation 112.48 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 1 | 47.74 hours | Geometric Coefficient of Variation 114.28 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 2 | 65.15 hours | Geometric Coefficient of Variation 104.61 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 1 | 83.24 hours | Geometric Coefficient of Variation 67.57 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 1 | 84.88 hours | Geometric Coefficient of Variation 61.54 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 2 | 47.12 hours | Geometric Coefficient of Variation 112.1 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 1 | 154.28 hours | Geometric Coefficient of Variation 54.214 |
| Dose Expansion Part: Bladder Cancer | Dose Escalation and Expansion Part: Tmax of Free MMAE | Cycle 2 | 125.38 hours | Geometric Coefficient of Variation 31.21 |
Secondary
Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage
Anti-tumor activity measured by the number of participants who experienced tumor shrinkage was not planned to be collected for the dose expansion part.
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Population: Full analysis set: all participants who had been exposed to tisotumab vedotin in the dose escalation part.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage | 0 Participants |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage | 0 Participants |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage | 0 Participants |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage | 1 Participants |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage | 0 Participants |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage | 2 Participants |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage | 1 Participants |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage | 3 Participants |
Secondary
Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF
PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2. AUC0-inf was only analyzed in the dose escalation part of the study. Data was not planned to be collected for the AUC0-inf of tisotumab vedotin and total HuMax-TF for the dose expansion part.
Time frame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
Population: PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 14.52 day*ug/mL | Geometric Coefficient of Variation 4.98 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 23.75 day*ug/mL | Geometric Coefficient of Variation 0.2 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 23.01 day*ug/mL | Geometric Coefficient of Variation 9.95 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 15.57 day*ug/mL | Geometric Coefficient of Variation 7.81 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 37.02 day*ug/mL | Geometric Coefficient of Variation 16.39 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 26.12 day*ug/mL | Geometric Coefficient of Variation 6.44 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 25.77 day*ug/mL | Geometric Coefficient of Variation 15.7 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 37.08 day*ug/mL | Geometric Coefficient of Variation 6.37 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 67.93 day*ug/mL | Geometric Coefficient of Variation 14.25 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 46.68 day*ug/mL | Geometric Coefficient of Variation 10.99 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 69.96 day*ug/mL | Geometric Coefficient of Variation 13.26 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 46.59 day*ug/mL | Geometric Coefficient of Variation 9.98 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 43.41 day*ug/mL | Geometric Coefficient of Variation 30.31 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 33.95 day*ug/mL | Geometric Coefficient of Variation 20.93 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 30.56 day*ug/mL | Geometric Coefficient of Variation 26.43 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 48.19 day*ug/mL | Geometric Coefficient of Variation 35.67 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 80.59 day*ug/mL | Geometric Coefficient of Variation 24.03 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 63.88 day*ug/mL | Geometric Coefficient of Variation 48.61 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 136.08 day*ug/mL | Geometric Coefficient of Variation 12.41 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 90.08 day*ug/mL | Geometric Coefficient of Variation 52.74 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 98.59 day*ug/mL | Geometric Coefficient of Variation 26.45 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 64.10 day*ug/mL | Geometric Coefficient of Variation 19.06 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 53.47 day*ug/mL | Geometric Coefficient of Variation 30.88 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 93.29 day*ug/mL | Geometric Coefficient of Variation 30.45 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 145.82 day*ug/mL | Geometric Coefficient of Variation 9.42 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 88.95 day*ug/mL | Geometric Coefficient of Variation 11.04 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 157.81 day*ug/mL | Geometric Coefficient of Variation 12.7 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 105.84 day*ug/mL | Geometric Coefficient of Variation 8.68 |
Secondary
Dose Escalation Part: AUC0-inf of Free MMAE
PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2. AUC0-inf was not planned to be collected for the dose expansion part. AUC0-inf was not calculated where the percentage of the AUC that was due to the extrapolation was more than 20%.
Time frame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
Population: PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation Part: AUC0-inf of Free MMAE | Cycle 1 | 12.63 day*ng/mL | Geometric Coefficient of Variation 12.44 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: AUC0-inf of Free MMAE | Cycle 1 | 13.93 day*ng/mL | — |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: AUC0-inf of Free MMAE | Cycle 2 | 22.32 day*ng/mL | Geometric Coefficient of Variation 43.62 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: AUC0-inf of Free MMAE | Cycle 1 | 16.32 day*ng/mL | Geometric Coefficient of Variation 57.56 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: AUC0-inf of Free MMAE | Cycle 1 | 20.39 day*ng/mL | — |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: AUC0-inf of Free MMAE | Cycle 2 | 31.40 day*ng/mL | — |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: AUC0-inf of Free MMAE | Cycle 2 | 31.43 day*ng/mL | — |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: AUC0-inf of Free MMAE | Cycle 1 | 27.08 day*ng/mL | Geometric Coefficient of Variation 58.96 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: AUC0-inf of Free MMAE | Cycle 2 | 33.23 day*ng/mL | — |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: AUC0-inf of Free MMAE | Cycle 1 | 25.29 day*ng/mL | — |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: AUC0-inf of Free MMAE | Cycle 1 | 78.31 day*ng/mL | — |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: AUC0-inf of Free MMAE | Cycle 1 | 63.03 day*ng/mL | — |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: AUC0-inf of Free MMAE | Cycle 2 | 58.95 day*ng/mL | — |
Secondary
Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF
Pharmacokinetic (PK) parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. Data was not collected to report or calculate clearance for the expansion phase.
Time frame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
Population: PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 1.02 mL/hr/kg | Geometric Coefficient of Variation 0.2 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 1.61 mL/hr/kg | Geometric Coefficient of Variation 7.79 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 1.05 mL/hr/kg | Geometric Coefficient of Variation 9.95 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 1.72 mL/hr/kg | Geometric Coefficient of Variation 4.98 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 0.98 mL/hr/kg | Geometric Coefficient of Variation 6.52 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 1.46 mL/hr/kg | Geometric Coefficient of Variation 15.23 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 1.44 mL/hr/kg | Geometric Coefficient of Variation 6.32 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 0.98 mL/hr/kg | Geometric Coefficient of Variation 16.9 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 0.69 mL/hr/kg | Geometric Coefficient of Variation 12.61 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 0.71 mL/hr/kg | Geometric Coefficient of Variation 13.41 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 1.07 mL/hr/kg | Geometric Coefficient of Variation 11.6 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 1.07 mL/hr/kg | Geometric Coefficient of Variation 10.45 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 1.84 mL/hr/kg | Geometric Coefficient of Variation 20.59 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 2.05 mL/hr/kg | Geometric Coefficient of Variation 26.8 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 1.40 mL/hr/kg | Geometric Coefficient of Variation 31.39 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 1.26 mL/hr/kg | Geometric Coefficient of Variation 31.29 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 1.17 mL/hr/kg | Geometric Coefficient of Variation 60.05 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 0.93 mL/hr/kg | Geometric Coefficient of Variation 24.03 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 0.81 mL/hr/kg | Geometric Coefficient of Variation 69.72 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 0.53 mL/hr/kg | Geometric Coefficient of Variation 12.41 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 1.56 mL/hr/kg | Geometric Coefficient of Variation 34.12 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 0.87 mL/hr/kg | Geometric Coefficient of Variation 33.85 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 0.82 mL/hr/kg | Geometric Coefficient of Variation 26.45 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 1.30 mL/hr/kg | Geometric Coefficient of Variation 19.06 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 0.61 mL/hr/kg | Geometric Coefficient of Variation 9.72 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 1.03 mL/hr/kg | Geometric Coefficient of Variation 11.34 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 0.56 mL/hr/kg | Geometric Coefficient of Variation 14.13 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 0.87 mL/hr/kg | Geometric Coefficient of Variation 8.93 |
Secondary
Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF
PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2. t1/2 was only analyzed for the dose escalation part of the study. Data was not planned to be collected for t1/2 of tisotumab vedotin and total HuMax-TF for the dose expansion part.
Time frame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
Population: PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 16.05 hours | Geometric Coefficient of Variation 27.93 |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 13.54 hours | Geometric Coefficient of Variation 5.5 |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 12.22 hours | Geometric Coefficient of Variation 11.61 |
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 18.34 hours | Geometric Coefficient of Variation 8.73 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 30.71 hours | Geometric Coefficient of Variation 27.65 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 29.53 hours | Geometric Coefficient of Variation 4.08 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 28.66 hours | Geometric Coefficient of Variation 30.64 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 23.50 hours | Geometric Coefficient of Variation 39.89 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 33.68 hours | Geometric Coefficient of Variation 1.74 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 40.37 hours | Geometric Coefficient of Variation 4.27 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 33.72 hours | Geometric Coefficient of Variation 6.26 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 42.52 hours | Geometric Coefficient of Variation 7.48 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 57.37 hours | Geometric Coefficient of Variation 8.65 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 41.06 hours | Geometric Coefficient of Variation 6.85 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 40.44 hours | Geometric Coefficient of Variation 4.69 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 56.77 hours | Geometric Coefficient of Variation 9.6 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 33.62 hours | Geometric Coefficient of Variation 14.5 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 42.18 hours | Geometric Coefficient of Variation 25.39 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 42.72 hours | Geometric Coefficient of Variation 34.62 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 32.42 hours | Geometric Coefficient of Variation 20.05 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 57.72 hours | Geometric Coefficient of Variation 17.47 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 47.89 hours | Geometric Coefficient of Variation 25.82 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 46.24 hours | Geometric Coefficient of Variation 53.11 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 32.15 hours | Geometric Coefficient of Variation 62.74 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 54.95 hours | Geometric Coefficient of Variation 5.32 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 51.06 hours | Geometric Coefficient of Variation 9.18 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 40.93 hours | Geometric Coefficient of Variation 11.48 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 39.89 hours | Geometric Coefficient of Variation 23.15 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 41.19 hours | Geometric Coefficient of Variation 34.02 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 66.05 hours | Geometric Coefficient of Variation 10.07 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 55.10 hours | Geometric Coefficient of Variation 27.36 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 48.93 hours | Geometric Coefficient of Variation 5.61 |
Secondary
Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE
PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2. T1/2 was determined only for the dose escalation part of the study.
Time frame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
Population: PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE | Cycle 1 | 95.15 hours | Geometric Coefficient of Variation 25.74 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE | Cycle 1 | 69.34 hours | — |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE | Cycle 2 | 69.65 hours | Geometric Coefficient of Variation 3.86 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE | Cycle 1 | 63.98 hours | Geometric Coefficient of Variation 2.24 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE | Cycle 1 | 62.58 hours | — |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE | Cycle 2 | 60.71 hours | — |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE | Cycle 2 | 70.20 hours | — |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE | Cycle 1 | 63.65 hours | Geometric Coefficient of Variation 7.86 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE | Cycle 2 | 78.94 hours | — |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE | Cycle 1 | 78.90 hours | — |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE | Cycle 1 | 57.74 hours | — |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE | Cycle 1 | 68.47 hours | — |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE | Cycle 2 | 63.92 hours | — |
Secondary
Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF
PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. Data was not planned to be collected for the volume of distribution of tisotumab vedotin and total HuMax-TF for the dose expansion part.
Time frame: Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
Population: PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 68.40 mL/kg | Geometric Coefficient of Variation 11.84 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 51.55 mL/kg | Geometric Coefficient of Variation 1.61 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 76.69 mL/kg | Geometric Coefficient of Variation 9.53 |
| Dose Escalation Part: 0.6 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 55.75 mL/kg | Geometric Coefficient of Variation 10.8 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 60.27 mL/kg | Geometric Coefficient of Variation 17.79 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 70.80 mL/kg | Geometric Coefficient of Variation 14.54 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 69.74 mL/kg | Geometric Coefficient of Variation 7.99 |
| Dose Escalation Part: 0.9 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 57.13 mL/kg | Geometric Coefficient of Variation 8.9 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 63.46 mL/kg | Geometric Coefficient of Variation 16.87 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 57.38 mL/kg | Geometric Coefficient of Variation 8.65 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 58.48 mL/kg | Geometric Coefficient of Variation 12.66 |
| Dose Escalation Part: 1.2 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 62.61 mL/kg | Geometric Coefficient of Variation 6.03 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 84.98 mL/kg | Geometric Coefficient of Variation 22.85 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 86.10 mL/kg | Geometric Coefficient of Variation 12.38 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 99.20 mL/kg | Geometric Coefficient of Variation 20.82 |
| Dose Escalation Part: 1.5 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 77.55 mL/kg | Geometric Coefficient of Variation 10.74 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 70.21 mL/kg | Geometric Coefficient of Variation 42.93 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 81.13 mL/kg | Geometric Coefficient of Variation 35.6 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 67.26 mL/kg | Geometric Coefficient of Variation 50.61 |
| Dose Escalation Part: 1.8 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 50.62 mL/kg | Geometric Coefficient of Variation 36.02 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 92.04 mL/kg | Geometric Coefficient of Variation 21.62 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 60.40 mL/kg | Geometric Coefficient of Variation 17.48 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 68.69 mL/kg | Geometric Coefficient of Variation 30.52 |
| Dose Escalation Part: 2.0 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 74.82 mL/kg | Geometric Coefficient of Variation 4.19 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 1 | 50.69 mL/kg | Geometric Coefficient of Variation 7.2 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Total HuMax-TF: Cycle 2 | 58.10 mL/kg | Geometric Coefficient of Variation 12.31 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 2 | 72.74 mL/kg | Geometric Coefficient of Variation 5.79 |
| Dose Escalation Part: 2.2 mg/kg | Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF | Tisotumab Vedotin: Cycle 1 | 61.46 mL/kg | Geometric Coefficient of Variation 18.07 |
Secondary
Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction Among Available Post-Baseline Sum of Lesion Measurements
Anti-tumor activity measured by maximum reduction among available post-baseline sum of lesion measurements was not planned to be collected for the dose escalation part.
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Population: The number of participants analyzed includes all participants with baseline and one post-baseline evaluable tumor assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation Part: 0.3 mg/kg | Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction Among Available Post-Baseline Sum of Lesion Measurements | 6.00 millimeter(s) |
| Dose Escalation Part: 0.6 mg/kg | Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction Among Available Post-Baseline Sum of Lesion Measurements | -8.50 millimeter(s) |
| Dose Escalation Part: 0.9 mg/kg | Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction Among Available Post-Baseline Sum of Lesion Measurements | 1.00 millimeter(s) |
| Dose Escalation Part: 1.2 mg/kg | Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction Among Available Post-Baseline Sum of Lesion Measurements | -2.00 millimeter(s) |
| Dose Escalation Part: 1.5 mg/kg | Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction Among Available Post-Baseline Sum of Lesion Measurements | 0.00 millimeter(s) |
| Dose Escalation Part: 1.8 mg/kg | Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction Among Available Post-Baseline Sum of Lesion Measurements | -4.00 millimeter(s) |
| Dose Escalation Part: 2.0 mg/kg | Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction Among Available Post-Baseline Sum of Lesion Measurements | -1.00 millimeter(s) |
Secondary
Dose Expansion Part: Duration of Response (DOR)
DOR was defined as the median time in weeks from when confirmed response was first documented until the first documented disease progression, or death from any cause, whichever was earliest as assessed by the investigator. A responder was defined as any participant with a best overall response of confirmed CR or PR.
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Population: All participants who had a confirmed response of either CR or PR and were considered a responder for the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation Part: 1.2 mg/kg | Dose Expansion Part: Duration of Response (DOR) | NA Weeks |
| Dose Expansion Part: Bladder Cancer | Dose Expansion Part: Duration of Response (DOR) | 32.0 Weeks |
| Dose Expansion Part: Cervical Cancer | Dose Expansion Part: Duration of Response (DOR) | 18.4 Weeks |
| Dose Expansion Part: Endometrial Cancer | Dose Expansion Part: Duration of Response (DOR) | NA Weeks |
| Dose Expansion Part: Esophageal Cancer | Dose Expansion Part: Duration of Response (DOR) | 18.3 Weeks |
| Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) | Dose Expansion Part: Duration of Response (DOR) | NA Weeks |
| Dose Expansion Part: Ovarian Cancer | Dose Expansion Part: Duration of Response (DOR) | 21.4 Weeks |