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

NCT03786081 | Terminated Phase 1 DMC FDA Drug

• 7 other identifiers: GCT1015-05InnovaTV 205MK-3475-834ENGOT-cx8GOG-3024KEYNOTE-8342017-004758-40
• Study Type: interventional
• Target: 214
• Locations: 10 countries
• Sites: 71

Brief Summary

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.

Conditions

Cervical Cancer

Keywords

cervical carcinoma

Outcome Measures

Primary Outcomes (2)

• Dose escalation: Dose Limiting Toxicities (DLTs)

  To establish the MTD and RP2D of tisotumab vedotin in combination

  DLTs will be identified during the first treatment cycle (21 day cycles)

• Dose expansion: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

  Objective response is defined as confirmed partial response (PR) or complete response (CR)

  approximately 2 years

Secondary Outcomes (12)

• Number of adverse events (AEs)

  up to 2 years

• Dose escalation: ORR per RECIST v1.1

  approximately 2 years

• Duration of Response (DOR) per RECIST v1.1 by investigator assessment

  approximately 2 years

• Time to Response (TTR) per RECIST v1.1 by investigator assessment

  approximately 2 years

• Progression free survival (PFS) per RECIST v1.1 by investigator assessment

  approximately 2 years

Study Arms (8)

A: Tisotumab Vedotin + bevacizumab

EXPERIMENTAL

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

Drug: Tisotumab Vedotin; Drug: Bevacizumab

B: Tisotumab vedotin + pembrolizumab

EXPERIMENTAL

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

Drug: Tisotumab Vedotin; Drug: Pembrolizumab

C: Tisotumab vedotin + carboplatin

EXPERIMENTAL

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

Drug: Tisotumab Vedotin; Drug: Carboplatin

D: Tisotumab vedotin + carboplatin

EXPERIMENTAL

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

Drug: Tisotumab Vedotin; Drug: Carboplatin

E: Tisotumab vedotin + pembrolizumab

EXPERIMENTAL

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

Drug: Tisotumab Vedotin; Drug: Pembrolizumab

F: Tisotumab vedotin + pembrolizumab

EXPERIMENTAL

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

Drug: Tisotumab Vedotin; Drug: Pembrolizumab

G: Tisotumab vedotin monotherapy

EXPERIMENTAL

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

Drug: Tisotumab Vedotin

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

EXPERIMENTAL

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

Drug: Tisotumab Vedotin; Drug: Bevacizumab; Drug: Pembrolizumab; Drug: Carboplatin

Interventions

Tisotumab Vedotin DRUG

Given into the vein (IV)

Also known as: TIVDAK

A: Tisotumab Vedotin + bevacizumab; B: Tisotumab vedotin + pembrolizumab; C: Tisotumab vedotin + carboplatin; D: Tisotumab vedotin + carboplatin; E: Tisotumab vedotin + pembrolizumab; F: Tisotumab vedotin + pembrolizumab; G: Tisotumab vedotin monotherapy; H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab

Bevacizumab DRUG

Given via IV

Also known as: Avastin

A: Tisotumab Vedotin + bevacizumab; H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab

Pembrolizumab DRUG

Given via IV

Also known as: KEYTRUDA®

B: Tisotumab vedotin + pembrolizumab; E: Tisotumab vedotin + pembrolizumab; F: Tisotumab vedotin + pembrolizumab; H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab

Carboplatin DRUG

Given via IV

Also known as: Paraplatin

C: Tisotumab vedotin + carboplatin; D: Tisotumab vedotin + carboplatin; H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• Seagen, a wholly owned subsidiary of Pfizer: lead
• Genmab: collaborator
• European Network of Gynaecological Oncological Trial Groups (ENGOT): collaborator
• Belgian Gynaecological Oncology Group: collaborator
• GOG Foundation: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (71)

Arizona Oncology Associates

Phoenix, Arizona, 85016, United States

Location

Univ California, Irvine Medical Center

Orange, California, 92868, United States

Location

Olive View - UCLA Research and Education Institute

Sylmar, California, 91342, United States

Location

Baptist MD Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

University of Chicago

Chicago, Illinois, 60525, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center

Westwood, Kansas, 66205, United States

Location

Oschner Clinic

New Orleans, Louisiana, 70121, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Billings Clinic Cancer Center

Billings, Montana, 59101, United States

Location

Montana Cancer Consortium

Billings, Montana, 59102, United States

Location

SUNY Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of North Carolina Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

University of Cincinnati Physicians Group

Cincinnati, Ohio, 45206, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University Wexner Medical Center

Hilliard, Ohio, 43026, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Brown University - Women's and Infant Hospital

Providence, Rhode Island, 02905, United States

Location

St Francis Hospital Cancer Center

Greenville, South Carolina, 29607, United States

Location

Huntsman Cancer Center

Salt Lake City, Utah, 84112, United States

Location

Carilion Clinic

Roanoke, Virginia, 24016, United States

Location

AZ Sint-Jan

Bruges, 8000, Belgium

Location

Cliniques universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Grand Hôpital de Charleroi

Charleroi, 6000, Belgium

Location

Universitair Ziekenhuis Antwerpen (UZA)

Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Universitaire Ziekenhuizen Leuven,

Leuven, Belgium

Location

Centre Hospitalier de l'Ardenne

Libramont, 6800, Belgium

Location

Centre Hospitalier Universitaire (CHU) de Liège

Liège, 4000, Belgium

Location

Grand Hôpital de Charleroi

Loverval, 6280, Belgium

Location

CHU UCL Namur

Namur, 5000, Belgium

Location

Sainte-Elisabeth

Namur, 5000, Belgium

Location

Fakultni nemocnice Olomouc

Olomouc, 775 20, Czechia

Location

Fakultni nemocnice Olomouc

Olomouc, 77520, Czechia

Location

Fakultni nemocnice Ostrava

Ostrava-Poruba, 70852, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 51, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 12851, Czechia

Location

Fakultni nemocnice Bulovka

Prague, 180 81, Czechia

Location

Nemocnice Na Bulovce

Prague, 18081, Czechia

Location

Rigshospitalet

Copenhagen, 5072, Denmark

Location

Cork University Hospital

Cork, Ireland

Location

Mater Misericordiae University Hospital

Dublin, D07 R2WY, Ireland

Location

Waterford Regional Hospital

Waterford, X91 ER8E, Ireland

Location

University Hospital Waterford

Waterford, Ireland

Location

Azienda Ospedaliera Cannizzaro

Catania, 95100, Italy

Location

IEO Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Istituto Nazionale Tumori Fondazione G. Pascale

Naples, 80131, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, 00168, Italy

Location

Amsterdam UMC, Locatie AMC

Amsterdam, 1105 AZ, Netherlands

Location

AMC Medical Research

Amsterdam, Netherlands

Location

Universitair Medisch Centrum Groningen (UMCG)

Groningen, 9713 GZ, Netherlands

Location

Radboudumc

Nijmegen, 6525 GA, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, 3015 CC, Netherlands

Location

Erasmus University Medical Center Rotterdam

Rotterdam, 3015, Netherlands

Location

UMC Utrecht

Utrecht, 3508 GA, Netherlands

Location

University Medical Center Utrecht (UMC Utrecht)

Utrecht, 3584, Netherlands

Location

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Universitario Virgen de la Arrixaca

El Palmar, 30120, Spain

Location

Hospital 12 De Octubre

Madrid, 28041, Spain

Location

Baskent University Adana Application and Research Center

Adana, 01220, Turkey (Türkiye)

Location

Baskent University Ankara Hospital

Ankara, 06490, Turkey (Türkiye)

Location

Velindre Cancer Centre

Cardiff, South Glamorgan, CF14 2TL, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, Strathclyde, G12 OYN, United Kingdom

Location

Royal Marsden Hospital- Sutton

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 37651655 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

tisotumab vedotin; Bevacizumab; pembrolizumab; Carboplatin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2018
• First Posted: December 24, 2018
• Study Start: February 27, 2019
• Primary Completion: March 19, 2026
• Study Completion: March 19, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-03

Locations

DK (1); BE (12); IE (4); ES (4); US (25); NL (8); IT (5); CZ (7); TU (2); GB (3)