TriangleNCT02001623 · CITED IN SOURCE DOCUMENTS
Tisotumab Vedotin (HuMax®-TF-ADC) Safety Study in Patients With Solid Tumors
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE1, PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2021-12-29
The purpose of the trial is to establish the tolerability of HuMax-TF-ADC in a mixed population of patients with specified solid tumors.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
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
Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF
Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF
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
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
Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE)
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
Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage
Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events
Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction Among Available Post-Baseline Sum of Lesion Measurements
Dose Escalation and Expansion Part: Percentage Change From Baseline in Prostate Specific Antigen (PSA)
Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125
Dose Escalation and Expansion Part: Objective Response Rate
Dose Escalation and Expansion Part: Disease Control Rate
Dose Escalation and Expansion Part: Progression Free Survival (PFS)
Dose Expansion Part: Duration of Response (DOR)
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- All arms of the trial (borh in escalation and expansion phase) will be administered tisotumab vedotin (HuMax-TF-ADC)
- intervention Names
- Drug: Tisotumab Vedotin (HuMax-TF-ADC)
- label
- Tisotumab Vedotin (HuMax-TF-ADC)
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Tisotumab Vedotin (HuMax-TF-ADC)
- name
- Tisotumab Vedotin (HuMax-TF-ADC)
- other Names
- TIVDAK
- type
- DRUG
Study design
- allocation
- NA
- intervention Model
- SEQUENTIAL
- intervention Model Description
- Escalation phase for dose finding followed by expansion phase
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 195
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events
- 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.
- description
- 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.
- measure
- Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events
- 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.
- secondary Outcomes
- description
- 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.
- measure
- Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values
- time Frame
- Day 1 to end of follow-up, up to a maximum of 60 weeks
- description
- 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.
- measure
- Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values
- time Frame
- Day 1 to end of follow-up, up to a maximum of 60 weeks
- description
- 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.
- measure
- Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values
- time Frame
- Day 1 to end of follow-up, up to a maximum of 60 weeks
- measure
- 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
- description
- 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.
- measure
- Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest
- time Frame
- Day 1 to end of follow-up, up to a maximum of 60 weeks
- description
- 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.
- measure
- Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event
- time Frame
- Day 1 to end of follow-up, up to a maximum of 60 weeks
- description
- 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.
- measure
- Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF
- 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)
- description
- 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.
- measure
- Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF
- 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)
- description
- 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.
- measure
- 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
- 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)
- description
- 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.
- measure
- Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF
- 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)
- description
- 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.
- measure
- Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF
- 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)
- description
- 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.
- measure
- Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF
- 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)
Full study description
- 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
Source references
- references
- citation
- de Bono JS, Concin N, Hong DS, Thistlethwaite FC, Machiels JP, Arkenau HT, Plummer R, Jones RH, Nielsen D, Windfeld K, Ghatta S, Slomovitz BM, Spicer JF, Yachnin J, Ang JE, Mau-Sorensen PM, Forster MD, Collins D, Dean E, Rangwala RA, Lassen U. Tisotumab vedotin in patients with advanced or metastatic solid tumours (InnovaTV 201): a first-in-human, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Mar;20(3):383-393. doi: 10.1016/S1470-2045(18)30859-3. Epub 2019 Feb 8.
- pmid
- 30745090
- type
- RESULT
- citation
- Feng S, Gunawan R, Passey C, Voellinger J, Polhamus D, Gerritsen A, O'Day C, Carret AS, Soumaoro I, Gupta M, Hanley WD. Exposure-safety Markov modeling of ocular adverse events in patient populations treated with tisotumab vedotin. J Pharmacokinet Pharmacodyn. 2025 Oct 3;52(5):55. doi: 10.1007/s10928-025-10003-w.
- pmid
- 41044356
- type
- DERIVED
- citation
- Passey C, Voellinger J, Gibiansky L, Gunawan R, Nicacio L, Soumaoro I, Hanley WD, Winter H, Gupta M. Exposure-safety and exposure-efficacy analyses for tisotumab vedotin for patients with locally advanced or metastatic solid tumors. CPT Pharmacometrics Syst Pharmacol. 2023 Sep;12(9):1262-1273. doi: 10.1002/psp4.13007. Epub 2023 Jul 26.
- pmid
- 37496366
- type
- DERIVED
- citation
- Hong DS, Concin N, Vergote I, de Bono JS, Slomovitz BM, Drew Y, Arkenau HT, Machiels JP, Spicer JF, Jones R, Forster MD, Cornez N, Gennigens C, Johnson ML, Thistlethwaite FC, Rangwala RA, Ghatta S, Windfeld K, Harris JR, Lassen UN, Coleman RL. Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer. Clin Cancer Res. 2020 Mar 15;26(6):1220-1228. doi: 10.1158/1078-0432.CCR-19-2962. Epub 2019 Dec 3.
- pmid
- 31796521
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- rent or metastatic cervical cancer who received at least one dose of TIVDAK at 2 mg/kg intravenously every 3 weeks in innovaTV 301, innovaTV 204, innovaTV 201 (NCT02001623), innovaTV 202 (NCT02552121), innovaTV 203 (NCT03245736), and innovaTV 206 (NCT03913741). The median duration of treatment with TIVDAK was 3.7 months (range: 0
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Preserved source evidence · Not medical advice