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 |
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Recruitment Status :
Active, not recruiting
First Posted : December 24, 2018
Last Update Posted : February 12, 2024
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Sponsor:
Seagen Inc.
Collaborators:
Genmab
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Belgian Gynaecological Oncology Group
GOG Foundation
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Seagen Inc.
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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 |
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 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 : | December 31, 2024 |
| Estimated Study Completion Date : | December 31, 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Cervical Cancer
Drug Information
available for:
Tisotumab vedotin
| Arm | Intervention/treatment |
|---|---|
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Experimental: A: Tisotumab Vedotin + bevacizumab
Dose escalation: Tisotumab vedotin in combination with bevacizumab once every three weeks in previously treated patients
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Drug: Tisotumab Vedotin
Given into the vein (IV)
Other Name: TIVDAK Drug: Bevacizumab Given via IV
Other Name: Avastin |
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Experimental: B: Tisotumab vedotin + pembrolizumab
Dose escalation: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients
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Drug: Tisotumab Vedotin
Given into the vein (IV)
Other Name: TIVDAK Drug: Pembrolizumab Given via IV
Other Name: KEYTRUDA® |
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Experimental: C: Tisotumab vedotin + carboplatin
Dose escalation: Tisotumab vedotin in combination with carboplatin once every three weeks in previously treated patients
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Drug: Tisotumab Vedotin
Given into the vein (IV)
Other Name: TIVDAK Drug: Carboplatin Given via IV
Other Name: Paraplatin |
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Experimental: D: Tisotumab vedotin + carboplatin
Dose expansion:Tisotumab vedotin in combination with carboplatin once every three weeks in previously untreated patients
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Drug: Tisotumab Vedotin
Given into the vein (IV)
Other Name: TIVDAK Drug: Carboplatin Given via IV
Other Name: Paraplatin |
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Experimental: E: Tisotumab vedotin + pembrolizumab
Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously untreated patients
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Drug: Tisotumab Vedotin
Given into the vein (IV)
Other Name: TIVDAK Drug: Pembrolizumab Given via IV
Other Name: KEYTRUDA® |
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Experimental: F: Tisotumab vedotin + pembrolizumab
Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients
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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.
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Drug: Tisotumab Vedotin
Given into the vein (IV)
Other Name: TIVDAK |
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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
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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 |
Primary Outcome Measures :
- 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
- 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 :
- 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.
- Dose escalation: ORR per RECIST v1.1 [ Time Frame: approximately 2 years ]Objective response is defined as confirmed PR or CR.
- 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.
- 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).
- 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.
- 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.
- Maximum concentration (Cmax) (All Arms except G) [ Time Frame: Up to 42 days ]Pharmacokinetic (PK) parameter
- Cmax (Arm G only) [ Time Frame: Up to 2 years ]PK parameter
- Trough Concentration (Ctrough) (All Arms) [ Time Frame: Up to 2 years ]PK parameter
- Area under the concentration-time curve (AUC) (All Arms except G) [ Time Frame: Through 21 days after first dose ]PK parameter
- AUC (Arm G only) [ Time Frame: Through 8 days after first dose ]PK parameter
- Anti-drug antibodies (ADAs) [ Time Frame: Up to 2 years ]
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, 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)
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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)
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
Show 72 study locations
Sponsors and Collaborators
Seagen Inc.
Genmab
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Belgian Gynaecological Oncology Group
GOG Foundation
Merck Sharp & Dohme LLC
| Responsible Party: | Seagen Inc. |
| ClinicalTrials.gov Identifier: | NCT03786081 |
| Other Study ID Numbers: |
GCT1015-05 InnovaTV 205 ( Other Identifier: Genmab ) MK-3475-834 ( Other Identifier: Merck Sharp & Dohme LLC ) ENGOT-cx8 ( Other Identifier: European Network of Gynaecological Oncological Trial ) GOG-3024 ( Other Identifier: GOG Foundation ) KEYNOTE-834 ( Other Identifier: Merck Sharp & Dohme LLC ) 2017-004758-40 ( EudraCT Number ) |
| First Posted: | December 24, 2018 Key Record Dates |
| Last Update Posted: | February 12, 2024 |
| Last Verified: | February 2024 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Seagen Inc.:
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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 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 |