Description:
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.
Title
- Brief Title: Safety and Efficacy of Tisotumab Vedotin Monotherapy & in Combination With Other Cancer Agents in Subjects With Cervical Cancer
- 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
Clinical Trial IDs
- ORG STUDY ID:
GCT1015-05
- SECONDARY ID:
InnovaTV 205
- SECONDARY ID:
MK3475 KN 834
- NCT ID:
NCT03786081
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Tisotumab Vedotin | | A: Tisotumab Vedotin + bevacizumab |
Bevacizumab | Avastin | A: Tisotumab Vedotin + bevacizumab |
Pembrolizumab | Keytruda | B: Tisotumab vedotin + pembrolizumab |
Carboplatin | Paraplatin | C: Tisotumab vedotin + carboplatin |
Purpose
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.
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).
Trial Arms
Name | Type | Description | Interventions |
---|
A: Tisotumab Vedotin + bevacizumab | Experimental | Dose escalation: Tisotumab vedotin in combination with bevacizumab once every three weeks in previously treated patients | - Tisotumab Vedotin
- Bevacizumab
|
B: Tisotumab vedotin + pembrolizumab | Experimental | Dose escalation: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients | - Tisotumab Vedotin
- Pembrolizumab
|
C: Tisotumab vedotin + carboplatin | Experimental | Dose escalation: Tisotumab vedotin in combination with carboplatin once every three weeks in previously treated patients | - Tisotumab Vedotin
- Carboplatin
|
D: Tisotumab vedotin + carboplatin | Experimental | Dose expansion:Tisotumab vedotin in combination with carboplatin once every three weeks in previously untreated patients | - Tisotumab Vedotin
- Carboplatin
|
E: Tisotumab vedotin + pembrolizumab | Experimental | Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously untreated patients | - Tisotumab Vedotin
- Pembrolizumab
|
F: Tisotumab vedotin + pembrolizumab | Experimental | Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients | - Tisotumab Vedotin
- Pembrolizumab
|
G: Tisotumab vedotin monotherapy | Experimental | Dose expansion: Tisotumab vedotin monotherapy weekly for three weeks and 1 week off (28 day treatment cycle) in previously treated patients. | |
Eligibility 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Dose escalation: Dose Limiting Toxicities (DLTs) |
Time Frame: | DLTs will be identified during the first treatment cycles (21 days cycles) |
Safety Issue: | |
Description: | To establish the MTD and RP2D of tisotumab vedotin in combination |
Secondary Outcome Measures
Measure: | Adverse events (AEs) |
Time Frame: | up to 2 years |
Safety Issue: | |
Description: | Frequency, duration, and severity of adverse events (AEs) |
Measure: | Objective Response Rate |
Time Frame: | approximately 2 years |
Safety Issue: | |
Description: | Objective Response Rate (ORR) based upon RECIST v1.1. |
Measure: | Duration of Response |
Time Frame: | approximately 2 years |
Safety Issue: | |
Description: | Duration of Response (DOR) based upon RECIST v1.1. |
Measure: | Time to Response |
Time Frame: | approximately 2 years |
Safety Issue: | |
Description: | Time to Response (TTR) based upon RECIST v1.1. |
Measure: | Progression free survival |
Time Frame: | approximately 2 years |
Safety Issue: | |
Description: | Progression free survival (PFS) based upon RECIST v1.1. |
Measure: | Overall Survival |
Time Frame: | approximately 2 years |
Safety Issue: | |
Description: | Overall Survival (OS) |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Seagen Inc. |
Trial Keywords
Last Updated
August 19, 2021