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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
214
Dose escalation: Dose Limiting Toxicities (DLTs)
To establish the MTD and RP2D of tisotumab vedotin in combination
Time frame: DLTs will be identified during the first treatment cycle (21 day cycles)
Dose expansion: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Objective response is defined as confirmed partial response (PR) or complete response (CR)
Time frame: approximately 2 years
Number of adverse events (AEs)
Any untoward medical occurrence in a clinical trial participant whether or not considered related to the medicinal product.
Time frame: up to 2 years
Dose escalation: ORR per RECIST v1.1
Objective response is defined as confirmed PR or CR.
Time frame: approximately 2 years
Duration of Response (DOR) per RECIST v1.1 by investigator assessment
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 frame: approximately 2 years
Time to Response (TTR) per RECIST v1.1 by investigator assessment
Will be calculated from the date of the first dose to the date of the initial documentation of response (CR or PR).
Time frame: approximately 2 years
Progression free survival (PFS) per RECIST v1.1 by investigator assessment
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.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Given via IV
Arizona Oncology Associates
Phoenix, Arizona, United States
Univ California, Irvine Medical Center
Orange, California, United States
Olive View - UCLA Research and Education Institute
Sylmar, California, United States
Baptist MD Anderson Cancer Center
Jacksonville, Florida, United States
Augusta University
Augusta, Georgia, United States
University of Chicago
Chicago, Illinois, United States
Indiana University School of Medicine
Indianapolis, Indiana, United States
University of Kansas Medical Center
Westwood, Kansas, United States
Oschner Clinic
New Orleans, Louisiana, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
...and 61 more locations
Time frame: approximately 2 years
Overall Survival (OS)
The time from the date of the first trial drug administration to the date of death due to any cause.
Time frame: approximately 2 years
Maximum concentration (Cmax) (All Arms except G)
Pharmacokinetic (PK) parameter
Time frame: Up to 42 days
Cmax (Arm G only)
PK parameter
Time frame: Up to 2 years
Trough Concentration (Ctrough) (All Arms)
PK parameter
Time frame: Up to 2 years
Area under the concentration-time curve (AUC) (All Arms except G)
PK parameter
Time frame: Through 21 days after first dose
AUC (Arm G only)
PK parameter
Time frame: Through 8 days after first dose
Anti-drug antibodies (ADAs)
Time frame: Up to 2 years