Ovary CancerPhase 1/2NCT02001623
Tisotumab Vedotin (HuMax®-TF-ADC) Safety Study in Patients With Solid Tumors
A Phase 1/2 study testing Tisotumab Vedotin (HuMax-TF-ADC) in people with Ovary Cancer and Cervix Cancer, run by Seagen Inc. at 29 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ovary Cancer, Cervix Cancer, Endometrium Cancer
- What is being tested?
- Tisotumab Vedotin (HuMax-TF-ADC)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 195 participants
- Where
- 29 sitesin 5 countries
- Study dates
- 30 Nov 2013to 2 May 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
29 sites in 5 countries.
29 sites in 5 countries
United Kingdom9 sites
Velindre NHS Trust
Cardiff, Wales, CF14 2TL
Beatson Cancer Centre
Glasgow, G12 OYN
The Leeds Teaching Hospitals NHS Trust
Leeds, England, LS9 7TF
University College London Hospitals
London, England, NW1 2BU
Sarah Cannon Research Institute - London
London, England, W1G 6AD
Guys hospital
London, SE1 9RT
The Christie NHS Foundation Trust
Manchester, M20 4BX
Newcastle Hospitals NHS Foundation Trust
Newcastle upon Tyne, Newcastle, NE7 7DN
The Royal Marsden NHS Foundation Trust
Sutton, Surrey, SM2 5PT
United States8 sites
University Gynecologic Oncology
Atlanta, Georgia, 30342
University of Virginia
Charlottesville, Virginia, 22908
MD Anderson Cancer Center
Houston, Texas, 77030
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
University of Miami
Miami, Florida, 33136
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Yale Cancer Center
New Haven, Connecticut, 06520
University of California Irvine Medical Center (UCIMC)
Orange, California, 92868-3201
Belgium8 sites
Saint-Luc University Hospital
Brussels, 1200
Grand Hôpital de Charleroi
Charleroi, Hainaut, 6000
Universitair Ziekenhuis Antwerpen
Edegem, Antwerpen, 2650
Universitair Ziekenhuis Leuven
Leuven, Flemish Brabant, 3000
CHU de Liège
Liège, 4000
Centre Hospitalier Universitaire Ambroise Paré
Mons, Hainaut, 7000
CHU UCL Namur - Sainte Elisabeth
Namur, 5000
CHU UCL Namur - site Godinne
Yvoir, Namur, 5530
Denmark2 sites
Rigshospitalet, Copenhagen University Hospital
Copenhagen, DK-2100
Herlev and Gentofte Hospital
Herlev, 2730
Sweden2 sites
Lungemedicinska Kliniken
Linköping, 58185
Karolinska Universitetssjukhuset
Stockholm, Solna, 17176
About this study
Official title: 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
The purpose of the trial is to establish the tolerability of HuMax-TF-ADC in a mixed population of patients with specified solid tumors.
Read the 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
- Conditions
- Ovary Cancer, Cervix Cancer, Endometrium Cancer, Bladder Cancer, Prostate Cancer (CRPC), Esophagus Cancer
- Being tested
- Tisotumab Vedotin (HuMax-TF-ADC)
- 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)
- Medical subject headings
- Ovarian Neoplasms, Uterine Cervical Neoplasms, Endometrial Neoplasms, Urinary Bladder Neoplasms, Prostatic Neoplasms, Esophageal Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tisotumab Vedotin (HuMax-TF-ADC)Drug
Also called TIVDAK
| Study group | Role | What they receive |
|---|---|---|
| Tisotumab Vedotin (HuMax-TF-ADC) | Experimental | All arms of the trial (borh in escalation and expansion phase) will be administered tisotumab vedotin (HuMax-TF-ADC) Receives: Drug: Tisotumab Vedotin (HuMax-TF-ADC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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.
Measured: 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 (27)
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.
Measured: Day 1 to end of follow-up, up to a maximum of 60 weeks
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.
Measured: Day 1 to end of follow-up, up to a maximum of 60 weeks
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.
Measured: 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 Skin Rash
Measured: 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
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.
Measured: Day 1 to end of follow-up, up to a maximum of 60 weeks
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.
Measured: Day 1 to end of follow-up, up to a maximum of 60 weeks
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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%.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: Day 1 to end of follow-up, up to a maximum of 60 weeks
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.
Measured: Day 1 to end of follow-up, up to a maximum of 60 weeks
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.
Measured: Day 1 to end of follow-up, up to a maximum of 60 weeks
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.
Measured: Day 1 to end of follow-up, up to a maximum of 60 weeks
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.
Measured: Day 1 to end of follow-up, up to a maximum of 60 weeks
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.
Measured: Day 1 to end of follow-up, up to a maximum of 60 weeks
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.
Measured: At 6, 12, 24 and 36 weeks
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
Measured: Day 1 to end of follow-up, up to a maximum of 60 weeks
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.
Measured: Day 1 to end of follow-up, up to a maximum of 60 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2013 (estimated)
- Study start30 Nov 2013
- Primary completion2 May 2019
- Study completion2 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Ovary CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Escalation phase for dose finding followed by expansion phase
- Masking
- None (open label)
- Enrolment
- 195 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seagen Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Genmab
- Responsible party
- Sponsor
- Investigators
- Johann de Bono, Professor, Principal investigator, The Institute of Cancer Research & The Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02001623
- Sponsor's protocol ID
- GEN701
- Other IDs
- innovaTV 201
- Status last verified
- Nov 2021
- First submitted
- 14 Nov 2013
- Last updated
- 29 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
Publications
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.
PubMed 30745090Feng 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.
PubMed 41044356Passey 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.
PubMed 37496366Hong 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.
PubMed 31796521
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02001623
- Acronym / sponsor ID
- GEN701
- Conditions
- Ovary Cancer, Cervix Cancer, Endometrium Cancer, Bladder Cancer, Prostate Cancer (CRPC), Esophagus Cancer
- 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)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 195 participants (actual)
- Lead sponsor
- Seagen Inc.Industry (pharma, biotech, devices)
- Collaborators
- Genmab
- Study start
- 30 Nov 2013 (actual)
- Primary completion
- 2 May 2019 (actual)
- Study completion
- 2 May 2019 (actual)
- First posted
- 5 Dec 2013 (estimated)
- Results
- Posted 29 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Escalation phase for dose finding followed by expansion phase
| Arm | Type | Receives |
|---|---|---|
| Tisotumab Vedotin (HuMax-TF-ADC) | Experimental | Drug: Tisotumab Vedotin (HuMax-TF-ADC)All arms of the trial (borh in escalation and expansion phase) will be administered tisotumab vedotin (HuMax-TF-ADC) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tisotumab Vedotin (HuMax-TF-ADC)Also: TIVDAK | Drug | Tisotumab Vedotin (HuMax-TF-ADC) |
Primary outcome
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.
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
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.
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.
27 secondary outcomes
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
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
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
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
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
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
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)
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)
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)
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)
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)
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)
Dose Escalation Part: Half-life (t1/2) 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)
Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE)
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)
Dose Escalation Part: AUC0-inf of Free MMAE
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)
Dose Escalation and Expansion Part: Cmax of Free MMAE
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)
Dose Escalation and Expansion Part: Tmax of Free MMAE
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)
Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE
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)
Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction Among Available Post-Baseline Sum of Lesion Measurements
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Dose Escalation and Expansion Part: Percentage Change From Baseline in Prostate Specific Antigen (PSA)
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Dose Escalation and Expansion Part: Objective Response Rate
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Dose Escalation and Expansion Part: Disease Control Rate
Time frame: At 6, 12, 24 and 36 weeks
Dose Escalation and Expansion Part: Progression Free Survival (PFS)
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Dose Expansion Part: Duration of Response (DOR)
Time frame: Day 1 to end of follow-up, up to a maximum of 60 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30745090de 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.
- Derived from this study: PubMed 41044356Feng 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.
- Derived from this study: PubMed 37496366Passey 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.
- Derived from this study: PubMed 31796521Hong 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Johann de Bono, Professor principal investigator
The Institute of Cancer Research & The Royal Marsden NHS Foundation Trust
29 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tisotumab Vedotin (HuMax-TF-ADC) in people with Ovary Cancer and Cervix Cancer, run by Seagen Inc. at 29 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United Kingdom, United States, Belgium, Denmark, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02001623, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2021.