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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03786081
Recruitment Status : Active, not recruiting
First Posted : December 24, 2018
Last Update Posted : January 11, 2023
Sponsor:
Collaborators:
Genmab
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Belgian Gynaecological Oncology Group
Gynecologic Oncology Group
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Seagen Inc.

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 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).

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 214 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 : September 30, 2024
Estimated Study Completion Date : September 30, 2024

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
Given into the vein (IV)
Other Name: TIVDAK

Drug: Bevacizumab
Given via IV
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
Given into the vein (IV)
Other Name: TIVDAK

Drug: Pembrolizumab
Given via IV
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
Given into the vein (IV)
Other Name: TIVDAK

Drug: Carboplatin
Given via IV
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
Given into the vein (IV)
Other Name: TIVDAK

Drug: Carboplatin
Given via IV
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
Given into the vein (IV)
Other Name: TIVDAK

Drug: Pembrolizumab
Given via IV
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
Given into the vein (IV)
Other Name: TIVDAK

Drug: Pembrolizumab
Given via IV
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
Given into the vein (IV)
Other Name: TIVDAK
Experimental: 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
 Drug: Tisotumab Vedotin
Given into the vein (IV)
Other Name: TIVDAK

Drug: Bevacizumab
Given via IV
Other Name: Avastin

Drug: Pembrolizumab
Given via IV
Other Name: Keytruda

Drug: Carboplatin
Given via IV
Other Name: Paraplatin


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 cycle (21 day cycles) ]
    To establish the MTD and RP2D of tisotumab vedotin in combination

  2. Dose expansion: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) [ Time Frame: approximately 2 years ]
    Objective response is defined as confirmed partial response (PR) or complete response (CR)


Secondary Outcome Measures :
  1. Number of adverse events (AEs) [ Time Frame: up to 2 years ]
    Any untoward medical occurrence in a clinical trial participant whether or not considered related to the medicinal product.

  2. Dose escalation: ORR per RECIST v1.1 [ Time Frame: approximately 2 years ]
    Objective response is defined as confirmed PR or CR.

  3. Duration of Response (DOR) per RECIST v1.1 by investigator assessment [ Time Frame: approximately 2 years ]
    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.

  4. Time to Response (TTR) per RECIST v1.1 by investigator assessment [ Time Frame: approximately 2 years ]
    Will be calculated from the date of the first dose to the date of the initial documentation of response (CR or PR).

  5. Progression free survival (PFS) per RECIST v1.1 by investigator assessment [ Time Frame: approximately 2 years ]
    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.

  6. Overall Survival (OS) [ Time Frame: approximately 2 years ]
    The time from the date of the first trial drug administration to the date of death due to any cause.

  7. Maximum concentration (Cmax) (All Arms except G) [ Time Frame: Up to 42 days ]
    Pharmacokinetic (PK) parameter

  8. Cmax (Arm G only) [ Time Frame: Up to 2 years ]
    PK parameter

  9. Trough Concentration (Ctrough) (All Arms) [ Time Frame: Up to 2 years ]
    PK parameter

  10. Area under the concentration-time curve (AUC) (All Arms except G) [ Time Frame: Through 21 days after first dose ]
    PK parameter

  11. AUC (Arm G only) [ Time Frame: Through 8 days after first dose ]
    PK parameter

  12. Anti-drug antibodies (ADAs) [ Time Frame: Up to 2 years ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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, 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)
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


Locations
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Sponsors and Collaborators
Seagen Inc.
Genmab
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Belgian Gynaecological Oncology Group
Gynecologic Oncology Group
Merck Sharp & Dohme LLC
More Information
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Layout table for additonal information
Responsible Party: Seagen Inc.
ClinicalTrials.gov Identifier: NCT03786081    
Other Study ID Numbers: GCT1015-05
InnovaTV 205 ( Other Identifier: Genmab )
MK3475 KN 834 ( Other Identifier: Merck )
ENGOT-cx8 ( Other Identifier: European Network of Gynaecological Oncological Trial )
GOG-3024 ( Other Identifier: GOG Foundation )
First Posted: December 24, 2018    Key Record Dates
Last Update Posted: January 11, 2023
Last Verified: January 2023

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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 Seagen Inc.:
cervical carcinoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Uterine Cervical Neoplasms
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
 Bevacizumab
Pembrolizumab
Tisotumab vedotin
Carboplatin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action