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

Cervical Cancer Clinical Trial

Official title:

A Phase 1b/2 Open-Label Trial of Tisotumab Vedotin (HuMax®-TF-ADC) Monotherapy and in Combination With Other Agents in Subjects With Recurrent or Stage IVB Cervical Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03786081
• Other study ID #: GCT1015-05
• Secondary ID: InnovaTV 205MK-3
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: February 27, 2019
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: Seagen Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 214
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Drug:
• Tisotumab Vedotin
Given into the vein (IV)
• Bevacizumab
Given via IV
• Pembrolizumab
Given via IV
• Carboplatin
Given via IV

Locations

Country	Name	City	State
Belgium	AZ Sint-Jan	Brugge
Belgium	Cliniques universitaires Saint-Luc	Brussels
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Grand Hôpital de Charleroi	Charleroi
Belgium	Universitair Ziekenhuis Antwerpen (UZA)	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitaire Ziekenhuizen Leuven,	Leuven
Belgium	UZ Leuven	Leuven
Belgium	Centre Hospitalier de l'Ardenne	Libramont
Belgium	Centre Hospitalier Universitaire (CHU) de Liège	Liège
Belgium	Grand Hôpital de Charleroi	Loverval
Belgium	CHU UCL Namur	Namur
Belgium	Sainte-Elisabeth	Namur
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice Ostrava	Ostrava-Poruba
Czechia	Fakultni nemocnice Bulovka	Praha
Czechia	Nemocnice Na Bulovce	Praha
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Denmark	Rigshospitalet	Copenhagen
Ireland	Cork University Hospital	Cork
Ireland	Mater Misericordiae University Hospital	Dublin
Ireland	University Hospital Waterford	Waterford
Ireland	Waterford Regional Hospital	Waterford
Italy	Azienda Ospedaliera Cannizzaro	Catania
Italy	IEO Istituto Europeo di Oncologia	Milano
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome
Netherlands	AMC Medical Research	Amsterdam
Netherlands	Amsterdam UMC, Locatie AMC	Amsterdam
Netherlands	Universitair Medisch Centrum Groningen (UMCG)	Groningen
Netherlands	Radboudumc	Nijmegen
Netherlands	Erasmus Medisch Centrum	Rotterdam
Netherlands	Erasmus University Medical Center Rotterdam	Rotterdam
Netherlands	UMC Utrecht	Utrecht
Netherlands	University Medical Center Utrecht (UMC Utrecht)	Utrecht
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Cordoba
Spain	Hospital Universitario Virgen de la Arrixaca	El Palmar
Spain	Hospital 12 De Octubre	Madrid
Turkey	Baskent University Adana Application and Research Center	Adana
Turkey	Baskent University Ankara Hospital	Ankara
United Kingdom	Velindre Cancer Centre	Cardiff	South Glamorgan
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Strathclyde
United Kingdom	Royal Marsden Hospital- Sutton	Sutton	Surrey
United States	Augusta University	Augusta	Georgia
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium	Billings	Montana
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	University of North Carolina Chapel Hill	Chapel Hill	North Carolina
United States	University of Chicago	Chicago	Illinois
United States	University of Cincinnati Physicians Group	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	St Francis Hospital Cancer Center	Greenville	South Carolina
United States	Ohio State University Wexner Medical Center	Hilliard	Ohio
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Oschner Clinic	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Univ California, Irvine Medical Center	Orange	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Arizona Oncology Associates	Phoenix	Arizona
United States	Magee-Womens Hospital of UPMC	Pittsburgh	Pennsylvania
United States	Brown University - Women's and Infant Hospital	Providence	Rhode Island
United States	Carilion Clinic	Roanoke	Virginia
United States	Huntsman Cancer Center	Salt Lake City	Utah
United States	Olive View - UCLA Research and Education Institute	Sylmar	California
United States	University of Kansas Medical Center	Westwood	Kansas

Sponsors (6)

Lead Sponsor	Collaborator
Seagen Inc.	Belgian Gynaecological Oncology Group, European Network of Gynaecological Oncological Trial Groups (ENGOT), Genmab, GOG Foundation, Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  Denmark,  Ireland,  Italy,  Netherlands,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Number of adverse events (AEs)	Any untoward medical occurrence in a clinical trial participant whether or not considered related to the medicinal product.	up to 2 years
Secondary	Dose escalation: ORR per RECIST v1.1	Objective response is defined as confirmed PR or CR.	approximately 2 years
Secondary	Duration of Response (DOR) per RECIST v1.1 by investigator assessment	Will be calculated from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (PD) or death.	approximately 2 years
Secondary	Time to Response (TTR) per RECIST v1.1 by investigator assessment	Will be calculated from the date of the first dose to the date of the initial documentation of response (CR or PR).	approximately 2 years
Secondary	Progression free survival (PFS) per RECIST v1.1 by investigator assessment	The time from the date of the first trial drug administration to the date of the first documented disease progression or death due to any cause.	approximately 2 years
Secondary	Overall Survival (OS)	The time from the date of the first trial drug administration to the date of death due to any cause.	approximately 2 years
Secondary	Maximum concentration (Cmax) (All Arms except G)	Pharmacokinetic (PK) parameter	Up to 42 days
Secondary	Cmax (Arm G only)	PK parameter	Up to 2 years
Secondary	Trough Concentration (Ctrough) (All Arms)	PK parameter	Up to 2 years
Secondary	Area under the concentration-time curve (AUC) (All Arms except G)	PK parameter	Through 21 days after first dose
Secondary	AUC (Arm G only)	PK parameter	Through 8 days after first dose
Secondary	Anti-drug antibodies (ADAs)		Up to 2 years