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

• Sponsor: Genmab
• Collaborators: Seattle Genetics, Inc.; European Network of Gynaecological Oncological Trial Groups (ENGOT); Belgian Gynaecological Oncology Group; Gynecologic Oncology Group; Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Genmab

Study Description

Brief Summary:

This is an open label, multi-center trial of tisotumab vedotin 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.

Condition or disease	Intervention/treatment	Phase
Cervical Cancer	Drug: Tisotumab Vedotin; Drug: Bevacizumab; Drug: Pembrolizumab; Drug: Carboplatin	Phase 1; Phase 2

Detailed Description:

The dose escalation part will occur in cervical cancer subjects 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 will consist of subjects with recurrent or stage IVB cervical cancer, who have not received prior systemic therapy for their recurrent or stage IVB disease, Arms D and E being treated with tisotumab vedotin + carboplatin or tisotumab vedotin + pembrolizumab, respectively, or subjects, who have progressed on or after standard of care treatments, Arm F treated with tisotumab vedotin + pembrolizumab. Subjects enrolled to these arms will receive the RP2D of tisotumab vedotin established in the dose escalation part.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 140 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b/2 Open-Label Trial of Tisotumab Vedotin (HuMax®-TF-ADC) in Combination With Other Agents in Subjects With Recurrent or Stage IVB Cervical Cancer
• Actual Study Start Date: February 27, 2019
• Estimated Primary Completion Date: April 2021
• Estimated Study Completion Date: April 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: A: Tisotumab Vedotin + bevacizumab; Dose escalation: Tisotumab vedotin in combination with bevacizumab once every three weeks in previously treated patients	Drug: Tisotumab Vedotin; i.v.; Drug: Bevacizumab; i.v.; Other Name: Avastin
Experimental: B: Tisotumab vedotin + pembrolizumab; Dose escalation: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients	Drug: Tisotumab Vedotin; i.v.; Drug: Pembrolizumab; i.v.; Other Name: Keytruda
Experimental: C: Tisotumab vedotin + carboplatin; Dose escalation: Tisotumab vedotin in combination with carboplatin once every three weeks in previously treated patients	Drug: Tisotumab Vedotin; i.v.; Drug: Carboplatin; i.v.; Other Name: Paraplatin
Experimental: D: Tisotumab vedotin + carboplatin; Dose expansion:Tisotumab vedotin in combination with carboplatin once every three weeks in previously untreated patients	Drug: Tisotumab Vedotin; i.v.; Drug: Carboplatin; i.v.; Other Name: Paraplatin
Experimental: E: Tisotumab vedotin + pembrolizumab; Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously untreated patients	Drug: Tisotumab Vedotin; i.v.; Drug: Pembrolizumab; i.v.; Other Name: Keytruda
Experimental: F: Tisotumab vedotin + pembrolizumab; Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients	Drug: Tisotumab Vedotin; i.v.; Drug: Pembrolizumab; i.v.; Other Name: Keytruda

Outcome Measures

Primary Outcome Measures :

1. Dose escalation: Dose Limiting Toxicities (DLTs) [ Time Frame: DLTs will be identified during the first treatment cycles (21 days cycles) ]
   To establish the MTD and RP2D of tisotumab vedotin in combination
2. Dose expansion: Evaluate the antitumor activity of tisotumab vedotin in combination in subjects with cervical cancer [ Time Frame: approximately 2 years ]
   Objective Response Rate (ORR) based upon RECIST v1.1.

Secondary Outcome Measures :

1. Adverse events (AEs) [ Time Frame: up to 2 years ]
   Frequency, duration, and severity of adverse events (AEs)
2. Objective Response Rate [ Time Frame: approximately 2 years ]
   Objective Response Rate (ORR) based upon RECIST v1.1.
3. Duration of Response [ Time Frame: approximately 2 years ]
   Duration of Response (DOR) based upon RECIST v1.1.
4. Time to Response [ Time Frame: approximately 2 years ]
   Time to Response (TTR) based upon RECIST v1.1.
5. Progression free survival [ Time Frame: approximately 2 years ]
   Progression free survival (PFS) based upon RECIST v1.1.
6. Overall Survival [ Time Frame: approximately 2 years ]
   Overall Survival (OS)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Patients with cervical cancer
• Accepts Healthy Volunteers: No

Criteria

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 and E only).
• Must have squamous, adenosquamous, or adenocarcinoma of the cervix and progressed on or after at least one but no more than two standard of care treatments for recurrent or stage IVB cervical cancer (Arm F only).
• Must have baseline measurable disease per RECIST v1.1.
• Must be at least 18 years of age on the day of signing informed consent (All Arms).
• 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
• Women 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 only)
• Recent (within 4 weeks of first dose of trial treatment) clinically significant gastrointestinal or vaginal bleeding requiring PRBC transfusion (Arm A only)
• Recent (within 4 weeks of first dose of trial treatment) evidence of wound healing complications that require medical intervention (Arm A 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

Contacts and Locations

Contacts

Contact: Genmab A/S Trial Information; +4570202728; clinicaltrials@genmab.com

Locations

United States, California

Univ California, Irvine Medical Center; Recruiting

Orange, California, United States, 92868

Contact: Sara Richards 714-509-9719 srichar4@uci.edu

Principal Investigator: Krishnansu Tewari, MD

United States, Illinois

University of Chicago; Recruiting

Chicago, Illinois, United States, 60525

Contact: Penny Dolan 773-702-3394 pdolan@babies.bsd.uchicago.edu

Principal Investigator: John Moroney, MD

United States, Kansas

University of Kansas Medical Center; Recruiting

Westwood, Kansas, United States, 66205

Contact: James Jeffrey 913-945-7549 jjeffery2@kumc.edu

Principal Investigator: Andrea Jewell, MD

United States, Massachusetts

Dana Farber; Recruiting

Boston, Massachusetts, United States, 02215

Contact: Victoria Engvold 617-632-2164 vengvold@partners.org

Principal Investigator: Susanna Campos, MD

United States, Montana

Montana Cancer Consortium; Recruiting

Billings, Montana, United States, 59102

Contact: Kelsey Skogen 406-435-7443 kskogen@billingsclinic.org

Principal Investigator: Benjamin Marchello, MD

United States, New York

Memorial Sloan Kettering Cancer Center; Recruiting

New York, New York, United States, 10065

Contact: Joyce Guillen 646-735-8278 guillenj@mskcc.org

Principal Investigator: Roisin O'Cearbhaill, MD

United States, Ohio

Cleveland Clinic; Recruiting

Cleveland, Ohio, United States, 44195

Contact: Claire Licina 216-445-5394 licinac@ccf.org

Principal Investigator: Peter Rose, MD

Ohio State University Wexner Medical Center; Recruiting

Hilliard, Ohio, United States, 43026

Contact: Molly Myers 614-685-6411 Molly.Myers@osumc.edu

Principal Investigator: David O'Malley, MD

United States, Pennsylvania

Fox Chase Cancer Center; Recruiting

Philadelphia, Pennsylvania, United States, 19111

Contact: Brittney Cirone 215-214-1667 Brittney.Cirone@fccc.edu

Principal Investigator: Christina Chu, MD

United States, Rhode Island

Women's and Infant Hospital; Recruiting

Providence, Rhode Island, United States, 02905

Contact: Janet Mari 401-274-1122 ext 48181 jmari@wihri.org

Principal Investigator: Cara Mathews, MD

Belgium

Cliniques universitaires Saint-Luc; Recruiting

Brussels, Belgium, 1200

Contact: Louise Favaretto +32 2 764 35 13 louise.favaretto@uclouvain.be

Principal Investigator: Jean-Francois Baurain, MD

Universitaire Ziekenhuizen Leuven,; Recruiting

Leuven, Belgium

Contact: Bo Vantilt +32 16 34 19 07 bo.vantilt@uzleuven.be

Principal Investigator: Ignace Vergote, Prof

Centre Hospitalier Universitaire de Liège; Recruiting

Liège, Belgium, 4000

Contact: Maude Piron +32 4 366 82 50 mpiron@chuliege.be

Principal Investigator: Christine Gennigens, MD

Denmark

Rigshospitalet; Recruiting

Copenhagen, Denmark, 5072

Contact: Ane Taudorf Nørmark +45 3545 6997 ane.taudorf.noermark.01@regionh.dk

Principal Investigator: Mansoor Mirza, MD

Sub-Investigator: Kristen Madsen, MD

Ireland

Cork University Hospital; Recruiting

Cork, Ireland

Contact: Edel Hassett 086-1728701 Edel.hassett@hse.ie

Principal Investigator: Dearbhaile Collins, MD

Mater Misericordiae University Hospital; Active, not recruiting

Dublin, Ireland, D07 R2WY D

University Hospital Waterford; Recruiting

Waterford, Ireland

Contact: Flordeliza Calacsan +353 51 848590 Flordeliza.calacsan@hse.ie

Principal Investigator: Paula Calvert, MD

Netherlands

AMC Medical Research; Recruiting

Amsterdam, Netherlands

Contact: Eva VanDalen trialmedonc@amc.uva.nl

Contact: Lyda ter Hofstede trialmedonc@amc.uva.nl

Principal Investigator: Anneke Westermann, MD

Universitair Medisch Centrum Groningen (UMCG); Recruiting

Groningen, Netherlands, 9713

Contact: B.T. Smit-Aeikema +31 50 361 3919 b.t.smit@umcg.nl

Principal Investigator: An Reyners, MD

Radboudumc; Active, not recruiting

Nijmegen, Netherlands, 6525 GA

Erasmus University Medical Center Rotterdam; Recruiting

Rotterdam, Netherlands, 3015

Contact: Cindy Bolder +310107034897 c.bolder@erasmusmc.nl

Principal Investigator: Ingrid Boere, MD

University Medical Center Utrecht (UMC Utrecht); Recruiting

Utrecht, Netherlands, 3584

Contact: Ellis van Liempt oncology-trialssecretariat@umcutrecht.nl

Principal Investigator: Eelke Gort, MD

Sponsors and Collaborators

Genmab

Seattle Genetics, Inc.

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Belgian Gynaecological Oncology Group

Gynecologic Oncology Group

Merck Sharp & Dohme Corp.

More Information

• Responsible Party: Genmab
• ClinicalTrials.gov Identifier: NCT03786081 History of Changes
• Other Study ID Numbers: GCT1015-05; InnovaTV 205 ( Other Identifier: Genmab ); MK3475 KN 834 ( Other Identifier: Merck )
• First Posted: December 24, 2018
• Last Update Posted: August 14, 2019
• Last Verified: August 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Genmab:

cervical carcinoma

Additional relevant MeSH terms:

Uterine Cervical Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Bevacizumab; Pembrolizumab; Carboplatin; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors