TriangleNCT02552121 · 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
- 2021-04-08
The purpose of the trial is to establish the tolerability of tisotumab vedotin (HuMax-TF-ADC) dosed three times every four weeks (3q4wk) in a mixed population of patients with specified solid tumors.
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
Part 1: Number of Participants Who Experience at Least One Adverse Event (AE)
Part 2: Number of Participants Who Experience at Least One Adverse Event (AE)
Part 1: Number of Participants Who Experienced at Least One or More Serious Adverse Event (SAE)
Part 2: Number of Participants Reporting One or More Serious Adverse Events (SAE)
Part 1: Number of Participants Reporting One or More Infusion-related Adverse Events
Part 2: Number of Participants Reporting One or More Infusion-related Adverse Events
Part 1: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events
Part 2: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events
Part 1: Number of Participants Reporting One or More Treatment-related Adverse Events
Part 2: Number of Participants Reporting One or More Treatment-related Adverse Events
Part 1: Number of Participants With Markedly Abnormal Laboratory Values
Part 2: Number of Participants With Markedly Abnormal Laboratory Values
Part 1: Number of Participants Who Experienced a Skin Rash
Part 2: Number of Participants Who Experienced a Skin Rash
Part 1: Number of Participants Who Experienced a Bleeding Event
Part 2: Number of Participants Who Experienced a Bleeding Event
Part 1: Number of Participants Who Experienced a Neuropathy Event
Part 2: Number of Participants Who Experienced a Neuropathy Event
Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC)
Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC)
Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Tisotumab Vedotin (HuMax-TF-ADC)
Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)
Part 2: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)
Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)
Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)
Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Tisotumab Vedotin (HuMax-TF-ADC)
Part 1: Terminal Phase Elimination Half-life (T1/2) for Tisotumab Vedotin (HuMax-TF-ADC)
Part 1: Total Clearance (CL) of Tisotumab Vedotin (HuMax-TF-ADC)
Part 1: Apparent Volume of Distribution (Vz) for Tisotumab Vedotin (HuMax-TF-ADC)
Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated)
Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated)
Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Total HuMax-TF (Conjugated and Non-conjugated)
Part 1: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)
Part 2: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)
Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)
Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated)
Part 1: Terminal Phase Elimination Half-life (T1/2) for Total HuMax-TF (Conjugated and Non-conjugated)
Part 1 and Part 2: Total Clearance (CL) of Total HuMax-TF (Conjugated and Non-conjugated)
Part 1 & Part 2: Apparent Volume of Distribution (Vz) for Total HuMax-TF (Conjugated and Non-conjugated)
Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Total HuMax-TF (Conjugated and Non-conjugated)
Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE)
Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE)
Part 1: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE)
Part 2: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE)
Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE)
Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE)
Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Free Toxin (MMAE)
Part 1: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result
Part 2: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result
Part 1: Number of Patients Who Experienced Anti-tumor Activity Measured by Tumor Shrinkage
Part 2: Anti-tumor Activity Measured by Percentage of Change in Sum of Lesion Measurements
Part 1: Response Evaluation Based on PSA (Prostate Specific Antigen [Prostate Cancer]): Percentage Change From Baseline to End of Study
Part 1: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study
Part 2: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study
Part 1: Best Overall Response (OR)
Part 2: Best Overall Response (OR)
Part 1: Number of Participants Who Experienced Disease Control
Part 2: Number of Participants Who Experienced Disease Control
Part 1: Progression Free Survival (PFS)
Part 2: Progression Free Survival (PFS)
Part 1: Duration of Response
Part 2: Duration of Response
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 according to RECIST v1.1 * Age ≥ 18 years. * Acceptable renal function. * Acceptable liver function. * Acceptable hematological status (hematologic support allowed under certain circumstances). * Acceptable coagulation status. * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Life expectancy of at least three months. * A negative serum pregnancy test (if female and aged between 18-55 years old). * Women who are pregnant or breast feeding are not to be included. * Patients, both females and males, of reproductive potential must agree to use adequate contraception during and for six months after the last infusion of HuMax-TF-ADC. * Following receipt of verbal and written information about the study, patients must provide signed informed consent before any study-related activity is carried out. Exclusion Criteria: * Known past or current coagulation defects. * Diffuse alveolar hemorrhage from vasculitis. * Known bleeding diathesis. * Ongoing major bleeding. * Trauma with increased risk of life-threatening bleeding. * Have clinically significant cardiac disease. * A baseline QT interval as corrected by Fridericia's formula (QTcF) \> 450 msec, a complete left bundle branch block (defined as a QRS interval ≥ 120 msec in left bundle branch block form) or an incomplete left bundle branch block. * Therapeutic anti-coagulative or long term anti-platelet treatment except use of low dose acetylsalicylic acid (ASA) up to 81 mg/day and non-ASA nonsteroidal anti-inflammatory drugs (NSAIDs). * Have received granulocyte colony stimulating factor (G-CSF) or granulocyte/macrophage colony stimulating factor support within one week or pegylated G-CSF within two weeks before the Screening Visit. * Have received a cumulative dose of corticosteroid ≥ 150 mg (prednisone or equivalent doses of corticosteroids) within two weeks before the first infusion. * No dietary supplements allowed during the study period, except multivitamins, vitamin D and calcium. * Major surgery within six weeks or open biopsy within 14 days before drug infusion. * Plan for any major surgery during treatment period. * Patients not willing or able to have a pre-trial tumor biopsy taken (the screening biopsy can be omitted if archived material is available). * Presence or anticipated requirement of epidural catheter in relation to infusions (within 48 hours before and after dose of trial drug). * Any history of intracerebral arteriovenous malformation, cerebral aneurysm, brain metastases or stroke. * Any anticancer therapy including; small molecules, immunotherapy, chemotherapy monoclonal antibodies or any other experimental drug within four weeks or five half lives, whichever is longest, before first infusion. * Prior treatment with bevacizumab within twelve weeks before the first infusion. * Prior therapy with a conjugated or unconjugated auristatin derivative. * Radiotherapy within 28 days prior to first dose. * Patients who have not recovered from symptomatic side effects of radiotherapy at the time of initiation of screening procedure. * Known past or current malignancy other than inclusion diagnosis, except for: * Cervical carcinoma of Stage 1B or less. * Non-invasive basal cell or squamous cell skin carcinoma. * Non-invasive, superficial bladder cancer. * Prostate cancer with a current PSA level \< 0.1 ng/mL. * Breast cancer in BRCA1 or BRACA2 positive ovarian cancer patients. * Any curable cancer with a complete response (CR) of \> 5 years duration. * Radiographic evidence of cavitating pulmonary lesions and tumor adjacent to or invading any large blood vessel unless approved by sponsor. * Ongoing, significant , uncontrolled medical condition. * Presence of peripheral neuropathy. * Active viral, bacterial or fungal infection requiring intravenous treatment with antimicrobial therapy starting less than four weeks prior to first dose. * Oral treatment with antimicrobial therapy starting less than two weeks prior to first dose. * Known human immunodeficiency virus seropositivity. * Positive serology (unless due to vaccination or passive immunization due to Ig therapy) for hepatitis B. * Positive serology for hepatitis C based on test at screening. * Inflammatory bowel disease including Crohn's disease and colitis ulcerosa. * Inflammatory lung disease including moderate and severe asthma and chronic obstructive pulmonary disease (COPD) requiring chronic medical therapy. * Ongoing acute or chronic inflammatory skin disease. * Active ocular surface disease at baseline (based on ophthalmological evaluation). * History of cicatricial conjunctivitis (as evaluated by an ophthalmologist).
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- 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)
- type
- DRUG
Study design
- allocation
- NA
- intervention Model
- SEQUENTIAL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 33
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
- measure
- Part 1: Number of Participants Who Experience at Least One Adverse Event (AE)
- time Frame
- Baseline to end of follow-up; maximum time of follow-up was 24 weeks
- description
- An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
- measure
- Part 2: Number of Participants Who Experience at Least One Adverse Event (AE)
- time Frame
- Baseline to end of trial (Part 2), up to 36 weeks
- description
- A SAE is defined as an AE that met one or more of the following criteria/outcomes which were classified as serious: Required inpatient hospitalization or prolongation of existing hospitalization. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Was a congenital anomaly/birth defect. Medically important determined by the investigator. Resulted in death. Was life-threatening.
- measure
- Part 1: Number of Participants Who Experienced at Least One or More Serious Adverse Event (SAE)
- time Frame
- Baseline to end of follow-up; maximum time of follow-up was 24 weeks
- description
- A SAE is defined as an AE that met one or more of the following criteria/outcomes which were classified as serious: Required inpatient hospitalization or prolongation of existing hospitalization. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Was a congenital anomaly/birth defect. Medically important determined by the investigator. Resulted in death. Was life-threatening.
- measure
- Part 2: Number of Participants Reporting One or More Serious Adverse Events (SAE)
- time Frame
- Baseline to end of trial (Part 2), up to 36 weeks
- description
- An infusion-related adverse event (AE) was defined as an AE occurring during infusion where the onset date and time of the event occurred within infusion time (+24 hours), and the event was judged as related to tisotumab vedotin by the investigator.
- measure
- Part 1: Number of Participants Reporting One or More Infusion-related Adverse Events
- time Frame
- Day 1, Day 8 & Day 15 (+1 day) until end of treatment (Part 1), approximately 48 weeks
- description
- An infusion-related adverse event (AE) was defined as an AE occurring during infusion where the onset date and time of the event occurred within infusion time (+24 hours), and the event was judged as related to tisotumab vedotin by the investigator.
- measure
- Part 2: Number of Participants Reporting One or More Infusion-related Adverse Events
- time Frame
- Day 1, Day 8 & Day 15 (+1 day) until end of trial (Part 2), up to 36 weeks
- description
- A CTCAE AE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator.
- measure
- Part 1: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events
- time Frame
- Baseline to end of follow-up; maximum time of follow-up was 24 weeks
- description
- A CTCAE AE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator.
- measure
- Part 2: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events
- time Frame
- Baseline to end of trial (Part 2), up to 36 weeks
- description
- A treatment-related AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; which has a causal relationship with the treatment.
- measure
- Part 1: Number of Participants Reporting One or More Treatment-related Adverse Events
- time Frame
- Baseline to end of follow-up; maximum time of follow-up was 24 weeks
- description
- A treatment-related AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; which has a causal relationship with the treatment.
- measure
- Part 2: Number of Participants Reporting One or More Treatment-related Adverse Events
- time Frame
- Baseline to end of trial (Part 2), up to 36 weeks
- secondary Outcomes
- description
- The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Markedly abnormal laboratory values are defined as any grade \>=3 laboratory abnormality events.
- measure
- Part 1: Number of Participants With Markedly Abnormal Laboratory Values
- time Frame
- Baseline to end of follow-up; maximum time of follow-up was 24 weeks
- description
- The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Markedly abnormal laboratory values are defined as any grade \>=3 laboratory abnormality events.
- measure
- Part 2: Number of Participants With Markedly Abnormal Laboratory Values
- time Frame
- Baseline to end of trial (Part 2), up to 36 weeks
- measure
- Part 1: Number of Participants Who Experienced a Skin Rash
- time Frame
- Baseline to end of follow-up; maximum time of follow-up was 24 weeks
- measure
- Part 2: Number of Participants Who Experienced a Skin Rash
- time Frame
- Baseline to end of trial (Part 2), up to 36 weeks
- measure
- Part 1: Number of Participants Who Experienced a Bleeding Event
- time Frame
- Baseline to end of trial (Part 1), up to 72 weeks
- measure
- Part 2: Number of Participants Who Experienced a Bleeding Event
- time Frame
- Baseline to end of trial (Part 2), up to 36 weeks
- measure
- Part 1: Number of Participants Who Experienced a Neuropathy Event
- time Frame
- Baseline to end of follow-up; maximum time of follow-up was 24 weeks
- measure
- Part 2: Number of Participants Who Experienced a Neuropathy Event
- time Frame
- Baseline to end of trial (Part 2), up to 36 weeks
- measure
- Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC)
- time Frame
- Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8 and 15, + 24 hours 1st infusion (Day 2), + 24 hours 3rd infusion (Day 16), + 72 hours 3rd infusion (Day 18), + 168 hours 3rd infusion (Day 22) of Cycle 1
- description
- Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
- measure
- Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC)
- time Frame
- Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1
- description
- Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase.
- measure
- Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Tisotumab Vedotin (HuMax-TF-ADC)
- time Frame
- Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8 and 15, + 24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), +168 hours 3rd infusion (Day 22) of Cycle 1
- measure
- Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC)
- time Frame
- Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1
Full study description
- brief Summary
- The purpose of the trial is to establish the tolerability of tisotumab vedotin (HuMax-TF-ADC) dosed three times every four weeks (3q4wk) in a mixed population of patients with specified solid tumors.
- detailed Description
- The study is conducted in two parts. In the Dose Escalation portion of the trial, subjects are enrolled into cohorts at increasing dose levels of tisotumab vedotin (HuMax-TF-ADC) in 28 day treatment cycles. The Cohort Expansion portion of the trial will further explore the recommended phase 2 dose of tisotumab vedotin (HuMax-TF-ADC) as determined in Part 1.
Source references
- references
- 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
Source notices and limitations
Discovery and provenance
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- 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: 0.4-40.2). In this pooled saf
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Preserved source evidence · Not medical advice