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

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ClinicalTrials.gov Identifier: NCT03786081
Recruitment Status : Recruiting
First Posted : December 24, 2018
Last Update Posted : October 5, 2020
Sponsor:
Collaborators:
Seagen 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
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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.


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 and Arm G treated with tisotumab vedotin alone. Subjects enrolled to Arms D, E, and F will receive the RP2D of tisotumab vedotin established in the dose escalation part. Subjects enrolled to Arm G will receive tisotumab vedotin weekly for three weeks and 1 week off (28 day treatment cycle).

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 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) Monotherapy and 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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cervical Cancer

Arms and Interventions
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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
Experimental: 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.
 Drug: Tisotumab Vedotin
i.v.


Outcome Measures
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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 monotherapy and 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
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
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 prior systemic therapies for recurrent or stage IVB cervical cancer (Arm F and G 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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03786081


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

Locations
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Sponsors and Collaborators
Genmab
Seagen Inc.
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Belgian Gynaecological Oncology Group
Gynecologic Oncology Group
Merck Sharp & Dohme Corp.
More Information
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Responsible Party: Genmab
ClinicalTrials.gov Identifier: NCT03786081    
Other Study ID Numbers: GCT1015-05
InnovaTV 205 ( Other Identifier: Genmab )
MK3475 KN 834 ( Other Identifier: Merck )
First Posted: December 24, 2018    Key Record Dates
Last Update Posted: October 5, 2020
Last Verified: October 2020

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