This trial will study tisotumab vedotin to find out whether it is an effective treatment alone or with other anticancer drugs for certain solid tumors and what side effects (unwanted effects) may occur. There are seven parts to this study. * In Part A, participants will receive tisotumab vedotin every 3 weeks (3-week cycles). * In Part B, participants will receive tisotumab vedotin on Days 1, 8, and 15 every 4-week cycle. * In Part C, participants will receive tisotumab vedotin on Days 1 and 15 of every 4-week cycle. * In Part D, participants will be given treatment on Day 1 of every 3-week cycle. * Participants in Part D will get tisotumab vedotin with either: * Pembrolizumab or, * Pembrolizumab and carboplatin, or * Pembrolizumab and cisplatin * In Part E, participants will receive tisotumab vedotin on Days 1 and 15 of every 4-week cycle. * In Part F, participants will receive tisotumab vedotin on Days 1, 15, and 29 of every 6-week cycle. Participants in Part F will get tisotumab vedotin with pembrolizumab. * In Part G, participants will receive tisotumab vedotin on Days 1, 15, and 29 of every 6-week cycle. Participants in Part G will get tisotumab vedotin with pembrolizumab and carboplatin. The objectives of the study have been achieved. Therefore, the study will transition to a long-term extension phase (LTEP). * In LTEP, participants still receiving clinical benefit based on the investigator's assessment and remaining on treatment may continue receiving treatment. * Participants will still receive tisotumab vedotin with either: * Pembrolizumab or, * Pembrolizumab and carboplatin, or * Pembrolizumab and cisplatin
The primary goal of this trial is to assess the activity, safety, and tolerability of tisotumab vedotin for the treatment of selected solid tumors. Patients will be treated with single agent tisotumab vedotin or tisotumab vedotin in combination with other anticancer agents. Patients who meet eligibility criteria will be enrolled into cohorts based on tumor type. Tumor types to be evaluated include colorectal cancer, squamous non-small cell lung cancer (sqNSCLC), exocrine pancreatic adenocarcinoma, and head and neck squamous cell carcinoma (HNSCC).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
352
Given into the vein (IV; intravenously)
200mg or 400mg given by IV
AUC 5mg/mL per minute or AUC 3.3mg/mL per minute given by IV
100mg/m\^2 given by IV
UCSD Medical Center - Encinitas
Encinitas, California, United States
UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)
La Jolla, California, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
UCSD Koman Family Outpatient Pavilion
La Jolla, California, United States
UC San Diego/Moores Cancer Center
La Jolla, California, United States
Confirmed Objective Response Rate (ORR) (Parts A, B, C, D, E, F, and G)
Proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the investigator
Time frame: Up to approximately 3 years
Incidence of Adverse Events (AEs)
Type, severity, and relatedness of adverse events. An AE is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Time frame: Up to approximately 3 years
Confirmed and Unconfirmed ORR
Proportion of patients who achieve a CR or PR according to RECIST v1.1 as assessed by the investigator
Time frame: Up to approximately 3 years
Disease Control Rate (DCR)
Proportion of patients who achieve a confirmed CR or PR according to RECIST v1.1 as assessed by the investigator, or meet the stable disease (SD) criteria at least once after start of study treatment at a minimum interval of 12 weeks
Time frame: Up to approximately 3 years
Duration of Response (DOR)
Time from the first documentation of objective response to the first documentation of PD or death due to any cause, whichever comes first, as assessed by the investigator
Time frame: Up to approximately 3 years
Time to Response (TTR)
Time from the start of study treatment to the first documentation of objective response, as assessed by investigator
Time frame: Up to approximately 1 year
Progression-free survival (PFS)
Time from the start of study treatment to the first documentation of PD according to RECIST v1.1 or death due to any cause, whichever comes first, as assessed by the investigator
Time frame: Up to approximately 3 years
Overall Survival (OS)
Time from the start of study treatment to date of death due to any cause
Time frame: Up to approximately 4 years
Cmax
Maximum observed plasma concentration
Time frame: Through 30-37 days following the last dose; up to approximately 3 years
Ctrough
Observed plasma concentration at the end of the dosing interval
Time frame: Through 30-37 days following the last dose; up to approximately 3 years
Incidence of anti-therapeutic antibodies (ATAs)
Time frame: Through 30-37 days following the last dose; up to approximately 3 years
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UCSD Shiley Eye Institute
La Jolla, California, United States
University of California Davis Medical Center
Sacramento, California, United States
University of California, Davis Comprehensive Cancer Center
Sacramento, California, United States
UC San Diego Medical Center- Hillcrest
San Diego, California, United States
UC San Diego Health - Rancho Bernardo
San Diego, California, United States
...and 162 more locations