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 : March 17, 2021
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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 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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 175 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 27, 2021 |
| Estimated Study Completion Date : | April 30, 2022 |
| 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
i.v. Drug: Bevacizumab i.v.
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
i.v. Drug: Pembrolizumab i.v.
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
i.v. Drug: Carboplatin i.v.
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
i.v. Drug: Carboplatin i.v.
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
i.v. Drug: Pembrolizumab i.v.
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
i.v. Drug: Pembrolizumab i.v.
Other Name: Keytruda |
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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
i.v. |
- 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
- 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.
- Adverse events (AEs) [ Time Frame: up to 2 years ]Frequency, duration, and severity of adverse events (AEs)
- Objective Response Rate [ Time Frame: approximately 2 years ]Objective Response Rate (ORR) based upon RECIST v1.1.
- Duration of Response [ Time Frame: approximately 2 years ]Duration of Response (DOR) based upon RECIST v1.1.
- Time to Response [ Time Frame: approximately 2 years ]Time to Response (TTR) based upon RECIST v1.1.
- Progression free survival [ Time Frame: approximately 2 years ]Progression free survival (PFS) based upon RECIST v1.1.
- Overall Survival [ Time Frame: approximately 2 years ]Overall Survival (OS)
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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
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
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| 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 ) |
| First Posted: | December 24, 2018 Key Record Dates |
| Last Update Posted: | March 17, 2021 |
| Last Verified: | March 2021 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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cervical carcinoma |
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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 |