Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

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Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Digestive System Diseases

Rare Diseases

Lung Neoplasms

Carcinoma

Carcinoma, Squamous Cell

Prostatic Neoplasms

Ovarian Neoplasms

Urinary Bladder Neoplasms

Squamous Cell Carcinoma of Head and Neck

Uterine Cervical Neoplasms

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Endometrial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Neoplasms, Squamous Cell

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Head and Neck Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Endocrine System Diseases

Gonadal Disorders

Esophageal Cancer

Ovarian Cancer

All Drugs and Chemicals

Coagulants

Antineoplastic Agents

Antibodies

Immunoglobulins

Thromboplastin

Tisotumab vedotin

Antineoplastic Agents, Immunological

All arms of the trial (borh in escalation and expansion phase) will be administered tisotumab vedotin (HuMax-TF-ADC)

Tisotumab Vedotin (HuMax-TF-ADC)

Johann de Bono, Professor

The purpose of the trial is to establish the tolerability of HuMax-TF-ADC in a mixed population of patients with specified solid tumors.

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

Escalation phase for dose finding followed by expansion phase

Tisotumab Vedotin (HuMax®-TF-ADC) Safety Study in Patients With Solid Tumors

First-in-human, Dose-escalating Safety Study of Tissue Factor Specific Antibody Drug Conjugate Tisotumab Vedotin (HuMax® TF ADC) in Patients With Locally Advanced and/or Metastatic Solid Tumors Known to Express Tissue Factor

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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%.

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.

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.

Anti-tumor activity measured by the number of participants who experienced tumor shrinkage was not planned to be collected for the dose expansion part.

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.

PSA was only assessed in participants with castrate-resistant prostate cancer.

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.

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.

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.

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

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.

Genmab

Seagen Inc.

Deaths from all causes are reported from day of enrollment to end of follow up (up to maximum of 60 weeks).

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.

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 IV infusion at a dose of 0.6 mg/kg of body weight.

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 0.9 mg/kg of body weight.

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 1.2 mg/kg of body weight.

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 1.5 mg/kg of body weight.

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 1.8 mg/kg of body weight.

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 2.0 mg/kg of body weight.

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 2.2 mg/kg of body weight.

Dose Escalation Part: 2.2 mg/kg

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.

Dose Expansion Part: Bladder 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.

Dose Expansion Part: Cervical 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.

Dose Expansion Part: Endometrial 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.

Dose Expansion Part: Esophageal Cancer

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.

Dose Expansion Part: Non-Small-Cell Lung 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.

Dose Expansion Part: Ovarian 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.

Dose Expansion Part: Prostate Cancer

Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC)

Total

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Full analysis set: all participants who had been exposed to tisotumab vedotin in either the dose escalation or expansion parts.

Clinical Trial Information

TEAEs

Serious TEAEs

Infusion-Related TEAEs

CTCAE Grade >=3 TEAEs

TEAEs Related to Study Drug

Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events

Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values

Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values

Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values

Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash

Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest

Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event

Tisotumab Vedotin: Cycle 1

Tisotumab Vedotin: Cycle 2

Total HuMax-TF: Cycle 1

Total HuMax-TF: Cycle 2

PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.

Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF

Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF

PK was only planned to be analyzed per the dose level received, not per cancer type. So the PK data is pooled for all participants in the dose expansion part of the study.

Dose Expansion Part: Pharmacokinetics (PK) Analysis Set

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

Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF

PK was only planned to be analyzed per the dose level received, not per cancer type. So the PK data is pooled for all participants in the dose expansion part of the study

Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF

Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF

Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF

Cycle 1

Cycle 2

Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE)

PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose

Dose Escalation Part: AUC0-inf of Free MMAE

Dose Escalation and Expansion Part: Cmax of Free MMAE

Dose Escalation and Expansion Part: Tmax of Free MMAE

Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE

Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin

Full analysis set: all participants who had been exposed to tisotumab vedotin in the dose escalation part.

Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage

Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events

The number of participants analyzed includes all participants with baseline and one post-baseline evaluable tumor assessment

Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction Among Available Post-Baseline Sum of Lesion Measurements

Analyses includes all participants with castrate-resistant prostate cancer who have a baseline and end of study evaluable assessment.

Dose Escalation and Expansion Part: Percentage Change From Baseline in Prostate Specific Antigen (PSA)

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 2.0mg/kg of body weight.

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.

Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125

Dose Escalation and Expansion Part: Objective Response Rate

Week 6

Week 12

Week 24

Week 36

Dose Escalation and Expansion Part: Disease Control Rate

Participants with documented disease progression and/or death are included.

Dose Escalation and Expansion Part: Progression Free Survival (PFS)

Dose Escalation Part: 0.3 mg/kgEdit 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.

Dose Escalation Part: 0.6 mg/kgEdit 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.

Dose Escalation Part: 0.9 mg/kgEdit 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.

All participants who had a confirmed response of either CR or PR and were considered a responder for the study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Tisotumab Vedotin (HuMax®-TF-ADC) Safety Study in Patients With Solid Tumors	NCT02001623	Ovary Cancer Cervix Cancer Endometrium Can... Bladder Cancer Prostate Cancer... Esophagus Cance... Lung Cancer(NSC... Squamous Cell C...	Tisotumab Vedot...	18 Years -	Seagen Inc.
Tisotumab Vedotin (HuMax®-TF-ADC) Safety Study in Patients With Solid Tumors	NCT02001623	Ovary Cancer Cervix Cancer Endometrium Can... Bladder Cancer Prostate Cancer... Esophagus Cance... Lung Cancer(NSC... Squamous Cell C...	Tisotumab Vedot...	18 Years -	Seagen Inc.

Spots Global Cancer Trial Database for lung cancer(nsclc)