Safety and Efficacy of Tisotumab Vedotin Monotherapy & in Combination With Other Cancer Agents in Subjects With Cervical Cancer

NCT ID: NCT03786081

Last Updated: 2025-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

214 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-27

Study Completion Date

2026-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This is an open label, multi-center trial of tisotumab vedotin monotherapy and in combination with bevacizumab, pembrolizumab, or carboplatin in subjects with recurrent or stage IVB cervical cancer.

The trial consists of two-parts a dose escalation part and an expansion part. The expansion part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) of the combinations have been determined in the dose escalation part.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The dose escalation part will occur in participants with cervical cancer who have progressed during or after standard of care therapy and who are intolerant or ineligible to receive standard of care treatments. Arm A will be conducted by escalating doses of both tisotumab vedotin and bevacizumab. Dose escalations of the tisotumab vedotin + pembrolizumab and tisotumab vedotin + carboplatin combinations (Arms B and C, respectively) will be conducted by combining fixed doses of either pembrolizumab or carboplatin with increasing doses of tisotumab vedotin.

The dose expansion part of this study (Arms D through H) will be conducted in 2 populations: participants with cervical cancer who have not received prior systemic therapy for recurrent or stage IVB cervical cancer (Arms D, E, and H) and participants with cervical cancer who have progressed on or after at least 1 but no more than 2 prior systemic therapies (Arms F and G).

Participants enrolled to Arms D, E, F and H will receive the RP2D of tisotumab vedotin established in the dose escalation part. Participants enrolled to Arm G will receive tisotumab vedotin weekly (at a dose lower than subjects in all other Arms) for three weeks and 1 week off (28-day treatment cycle).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cervical Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

A: Tisotumab Vedotin + bevacizumab

Dose escalation: Tisotumab vedotin in combination with bevacizumab once every three weeks in previously treated patients

Group Type EXPERIMENTAL

Tisotumab Vedotin

Intervention Type DRUG

Given into the vein (IV)

Bevacizumab

Intervention Type DRUG

Given via IV

B: Tisotumab vedotin + pembrolizumab

Dose escalation: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients

Group Type EXPERIMENTAL

Tisotumab Vedotin

Intervention Type DRUG

Given into the vein (IV)

Pembrolizumab

Intervention Type DRUG

Given via IV

C: Tisotumab vedotin + carboplatin

Dose escalation: Tisotumab vedotin in combination with carboplatin once every three weeks in previously treated patients

Group Type EXPERIMENTAL

Tisotumab Vedotin

Intervention Type DRUG

Given into the vein (IV)

Carboplatin

Intervention Type DRUG

Given via IV

D: Tisotumab vedotin + carboplatin

Dose expansion:Tisotumab vedotin in combination with carboplatin once every three weeks in previously untreated patients

Group Type EXPERIMENTAL

Tisotumab Vedotin

Intervention Type DRUG

Given into the vein (IV)

Carboplatin

Intervention Type DRUG

Given via IV

E: Tisotumab vedotin + pembrolizumab

Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously untreated patients

Group Type EXPERIMENTAL

Tisotumab Vedotin

Intervention Type DRUG

Given into the vein (IV)

Pembrolizumab

Intervention Type DRUG

Given via IV

F: Tisotumab vedotin + pembrolizumab

Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients

Group Type EXPERIMENTAL

Tisotumab Vedotin

Intervention Type DRUG

Given into the vein (IV)

Pembrolizumab

Intervention Type DRUG

Given via IV

G: Tisotumab vedotin monotherapy

Dose expansion: Tisotumab vedotin monotherapy weekly for three weeks and 1 week off (28 day treatment cycle) in previously treated patients.

Group Type EXPERIMENTAL

Tisotumab Vedotin

Intervention Type DRUG

Given into the vein (IV)

H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab

Dose expansion: Tisotumab vedotin in combination with pembrolizumab and carboplatin with or without bevacizumab once every three weeks in previously untreated patients

Group Type EXPERIMENTAL

Tisotumab Vedotin

Intervention Type DRUG

Given into the vein (IV)

Bevacizumab

Intervention Type DRUG

Given via IV

Pembrolizumab

Intervention Type DRUG

Given via IV

Carboplatin

Intervention Type DRUG

Given via IV

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Tisotumab Vedotin

Given into the vein (IV)

Intervention Type DRUG

Bevacizumab

Given via IV

Intervention Type DRUG

Pembrolizumab

Given via IV

Intervention Type DRUG

Carboplatin

Given via IV

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

TIVDAK Avastin KEYTRUDA® Paraplatin

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Must have squamous, adenosquamous, or adenocarcinoma of the cervix and progressed on or after standard of care treatments or are ineligible or intolerant to standard of care for recurrent or stage IVB cervical cancer (Arms A, B and C only).
* Must have squamous, adenosquamous, or adenocarcinoma of the cervix and must not have received prior systemic therapy for recurrent or stage IVB cervical cancer (Arms D, E, and H only).
* Must have squamous, adenosquamous, or adenocarcinoma of the cervix and progressed on or after at least one but no more than two prior systemic therapies for recurrent or stage IVB cervical cancer (Arms F and G only).
* Must have baseline measurable disease per RECIST v1.1.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (All Arms).
* Is not pregnant, breastfeeding, or expecting to conceive children within the projected duration of the trial and for at least 6 months after the last trial treatment administration
* Participants of childbearing potential must agree to use adequate contraception during and for 6 months after the last dose of trial treatment administration.
* Must sign an informed consent form (ICF) indicating the trial subject understands the purpose of and procedures required for the trial and are willing to participate in the trial (All Arms).

Exclusion Criteria

* Has clinically relevant bilateral hydronephrosis which cannot be alleviated by ureteral stents or percutaneous drainage. (All Arms)
* Has clinical signs or symptoms of gastrointestinal obstruction and requires parenteral hydration and/or nutrition. Post-operative obstructions within 4 weeks of abdominal surgery are permitted. (All Arms)
* Has clinically significant bleeding issues or risks

* Prior history (within 3 months) or current evidence of hemoptysis (1/2 teaspoon or more) (Arm A and bevacizumab-eligible participants in Arm H)
* Recent (within 4 weeks of first dose of trial treatment) clinically significant gastrointestinal or vaginal bleeding requiring PRBC transfusion (Arms A and H only)
* Recent (within 4 weeks of first dose of trial treatment) evidence of wound healing complications that require medical intervention (Arms A and H only)
* Has active ocular surface disease at baseline. Subjects with prior history of cicatricial conjunctivitis are ineligible (All Arms).
* Clinically significant cardiac disease
* Requires anti-coagulation therapy (Arms A and H only)
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Genmab

INDUSTRY

Sponsor Role collaborator

European Network of Gynaecological Oncological Trial Groups (ENGOT)

OTHER

Sponsor Role collaborator

Belgian Gynaecological Oncology Group

OTHER

Sponsor Role collaborator

GOG Foundation

NETWORK

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Seagen, a wholly owned subsidiary of Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Arizona Oncology Associates

Phoenix, Arizona, United States

Site Status

Univ California, Irvine Medical Center

Orange, California, United States

Site Status

Olive View - UCLA Research and Education Institute

Sylmar, California, United States

Site Status

Baptist MD Anderson Cancer Center

Jacksonville, Florida, United States

Site Status

Augusta University

Augusta, Georgia, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Indiana University School of Medicine

Indianapolis, Indiana, United States

Site Status

University of Kansas Medical Center

Westwood, Kansas, United States

Site Status

Oschner Clinic

New Orleans, Louisiana, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Billings Clinic Cancer Center

Billings, Montana, United States

Site Status

Montana Cancer Consortium

Billings, Montana, United States

Site Status

SUNY Downstate Medical Center

Brooklyn, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

University of North Carolina Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

University of Cincinnati Physicians Group

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Ohio State University Wexner Medical Center

Hilliard, Ohio, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Brown University - Women's and Infant Hospital

Providence, Rhode Island, United States

Site Status

St Francis Hospital Cancer Center

Greenville, South Carolina, United States

Site Status

Huntsman Cancer Center

Salt Lake City, Utah, United States

Site Status

Carilion Clinic

Roanoke, Virginia, United States

Site Status

AZ Sint-Jan

Bruges, , Belgium

Site Status

Cliniques universitaires Saint-Luc

Brussels, , Belgium

Site Status

Grand Hôpital de Charleroi

Charleroi, , Belgium

Site Status

Universitair Ziekenhuis Antwerpen (UZA)

Edegem, , Belgium

Site Status

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Universitaire Ziekenhuizen Leuven,

Leuven, , Belgium

Site Status

Centre Hospitalier de l'Ardenne

Libramont, , Belgium

Site Status

Centre Hospitalier Universitaire (CHU) de Liège

Liège, , Belgium

Site Status

Grand Hôpital de Charleroi

Loverval, , Belgium

Site Status

CHU UCL Namur

Namur, , Belgium

Site Status

Sainte-Elisabeth

Namur, , Belgium

Site Status

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Site Status

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Site Status

Fakultni nemocnice Ostrava

Ostrava-Poruba, , Czechia

Site Status

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

Site Status

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

Site Status

Fakultni nemocnice Bulovka

Prague, , Czechia

Site Status

Nemocnice Na Bulovce

Prague, , Czechia

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

Cork University Hospital

Cork, , Ireland

Site Status

Mater Misericordiae University Hospital

Dublin, , Ireland

Site Status

Waterford Regional Hospital

Waterford, , Ireland

Site Status

University Hospital Waterford

Waterford, , Ireland

Site Status

Azienda Ospedaliera Cannizzaro

Catania, , Italy

Site Status

IEO Istituto Europeo di Oncologia

Milan, , Italy

Site Status

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, , Italy

Site Status

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, , Italy

Site Status

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, , Italy

Site Status

Amsterdam UMC, Locatie AMC

Amsterdam, , Netherlands

Site Status

AMC Medical Research

Amsterdam, , Netherlands

Site Status

Universitair Medisch Centrum Groningen (UMCG)

Groningen, , Netherlands

Site Status

Radboudumc

Nijmegen, , Netherlands

Site Status

Erasmus Medisch Centrum

Rotterdam, , Netherlands

Site Status

Erasmus University Medical Center Rotterdam

Rotterdam, , Netherlands

Site Status

UMC Utrecht

Utrecht, , Netherlands

Site Status

University Medical Center Utrecht (UMC Utrecht)

Utrecht, , Netherlands

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario Reina Sofia

Córdoba, , Spain

Site Status

Hospital Universitario Virgen de la Arrixaca

El Palmar, , Spain

Site Status

Hospital 12 De Octubre

Madrid, , Spain

Site Status

Baskent University Adana Application and Research Center

Adana, , Turkey (Türkiye)

Site Status

Baskent University Ankara Hospital

Ankara, , Turkey (Türkiye)

Site Status

Velindre Cancer Centre

Cardiff, South Glamorgan, United Kingdom

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, Strathclyde, United Kingdom

Site Status

Royal Marsden Hospital- Sutton

Sutton, Surrey, United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Belgium Czechia Denmark Ireland Italy Netherlands Spain Turkey (Türkiye) United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Vergote I, Van Nieuwenhuysen E, O'Cearbhaill RE, Westermann A, Lorusso D, Ghamande S, Collins DC, Banerjee S, Mathews CA, Gennigens C, Cibula D, Tewari KS, Madsen K, Kose F, Jackson AL, Boere IA, Scambia G, Randall LM, Sadozye A, Baurain JF, Gort E, Zikan M, Denys HG, Ottevanger N, Forget F, Mondrup Andreassen C, Eaton L, Chisamore MJ, Viana Nicacio L, Soumaoro I, Monk BJ. Tisotumab Vedotin in Combination With Carboplatin, Pembrolizumab, or Bevacizumab in Recurrent or Metastatic Cervical Cancer: Results From the innovaTV 205/GOG-3024/ENGOT-cx8 Study. J Clin Oncol. 2023 Dec 20;41(36):5536-5549. doi: 10.1200/JCO.23.00720. Epub 2023 Aug 31.

Reference Type DERIVED
PMID: 37651655 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

InnovaTV 205

Identifier Type: OTHER

Identifier Source: secondary_id

MK-3475-834

Identifier Type: OTHER

Identifier Source: secondary_id

ENGOT-cx8

Identifier Type: OTHER

Identifier Source: secondary_id

GOG-3024

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-834

Identifier Type: OTHER

Identifier Source: secondary_id

2017-004758-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GCT1015-05

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.