Efficacy And Safety Study Of Tisotumab Vedotin For Patients With Solid Tumors

Study Overview

Efficacy and Safety Study of Tisotumab Vedotin for Patients With Solid Tumors

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, the treatment will be given to participants 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 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).

Colorectal Neoplasms
Carcinoma, Non-Small-Cell Lung
Exocrine Pancreatic Cancer
Carcinoma, Squamous Cell of Head and Neck

DRUG: tisotumab vedotin
DRUG: pembrolizumab
DRUG: carboplatin
DRUG: cisplatin

SGNTV-001
C5721001 (OTHER Identifier) (OTHER: Alias Study Number)
2023-503812-34-00 (REGISTRY Identifier) (REGISTRY: CTIS (EU))

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2018-03-08	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-09-11
First Submitted that Met QC Criteria 2018-03-26	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2025-09-12
First Posted (ESTIMATED) 2018-04-02	Results First Posted N/A	Last Verified 2025-09

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Part A: Tisotumab Vedotin - Q3W Schedule Tisotumab Vedotin on Day 1 of every 21-day cycle in participants with various solid tumors in 2L+	DRUG: tisotumab vedotin Given into the vein (IV; intravenously)
EXPERIMENTAL: Part B: Tisotumab Vedotin - 3Q4W Schedule Tisotumab Vedotin on Days 1, 8, and 15 of 28-day cycle in participants with various solid tumors in 2L+	DRUG: tisotumab vedotin Given into the vein (IV; intravenously)
EXPERIMENTAL: Part C: Tisotumab Vedotin - 2Q4W Schedule Tisotumab Vedotin on Days 1 and 15 of every 28-day cycle in participants with HNSCC or sqNSCLC in 2L+	DRUG: tisotumab vedotin Given into the vein (IV; intravenously)
EXPERIMENTAL: Part D: Tisotumab Vedotin Combination Therapy - Q3W Schedule Tisotumab Vedotin + pembrolizumab + (carboplatin or cisplatin). Given on Day 1 of every 21-day cycle in participants with various solid tumors in 1L HNSCC or sqNSCLC	DRUG: tisotumab vedotin Given into the vein (IV; intravenously) DRUG: pembrolizumab 200mg or 400mg given by IV DRUG: carboplatin AUC 5mg/mL per minute or AUC 3.3mg/mL per minute given by IV DRUG: cisplatin 100mg/m^2 given by IV
EXPERIMENTAL: Part E: Tisotumab Vedotin - 2Q4W Schedule Tisotumab Vedotin on Days 1 and 15 of every 28-day cycle in participants with HNSCC in the second- or third-line setting	DRUG: tisotumab vedotin Given into the vein (IV; intravenously)
EXPERIMENTAL: Part F: Tisotumab Vedotin Combination Therapy - Q2W Schedule Tisotumab Vedotin + pembrolizumab. Tisotumab Vedotin given on Days 1, 15, and 29 of every 6-week cycle. Pembrolizumab given on Day 1 of every 6-week cycle in participants with HNSCC in the first line setting	DRUG: pembrolizumab 200mg or 400mg given by IV
EXPERIMENTAL: Part G: Tisotumab Vedotin Combination Therapy - Q2W Schedule Tisotumab Vedotin + pembrolizumab + carboplatin. Tisotumab Vedotin and carboplatin given on Days 1, 15, and 29 of every 6-week cycle. Pembrolizumab given on Day 1 of every 6-week cycle in participants with HNSCC in the first line setting	DRUG: pembrolizumab 200mg or 400mg given by IV DRUG: carboplatin AUC 5mg/mL per minute or AUC 3.3mg/mL per minute given by IV

Primary Outcome Measures	Measure Description	Time Frame
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	Up to approximately 3 years

Secondary Outcome Measures	Measure Description	Time Frame
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.	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	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	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	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	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	Up to approximately 3 years
Overall Survival (OS)	Time from the start of study treatment to date of death due to any cause	Up to approximately 4 years
Cmax	Maximum observed plasma concentration	Through 30-37 days following the last dose; up to approximately 3 years
Ctrough	Observed plasma concentration at the end of the dosing interval	Through 30-37 days following the last dose; up to approximately 3 years
Incidence of anti-therapeutic antibodies (ATAs)		Through 30-37 days following the last dose; up to approximately 3 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Parts A, B, and C

Relapsed, locally-advanced or metastatic colorectal or pancreatic cancer, sqNSCLC, or HNSCC participants who are not candidates for standard therapy.
All participants must have experienced disease progression on or after their most recent systemic therapy.
Colorectal cancer (closed to enrollment): participants must have received prior therapy with each of following agents, if eligible: a fluoropyrimidine, oxaliplatin, irinotecan, and/or bevacizumab. Participants should have received no more than 3 systemic regimens in the metastatic setting.
sqNSCLC (closed to enrollment): Participants with NSCLC must have predominant squamous histology. Participants must have received prior therapy with a platinum-based treatment and a checkpoint inhibitor (CPI), if eligible. Participants should have received no more than 3 lines of systemic therapy in the metastatic setting.

Participants eligible for a tyrosine kinase inhibitor should have received such therapy. These participants should have received no more than 4 lines of systemic therapy in the metastatic setting.
Exocrine pancreatic adenocarcinoma (closed to enrollment): Participants with exocrine pancreatic adenocarcinoma must have predominant adenocarcinoma histology. Participants must have received prior therapy with a gemcitabine-based or 5FU-based regimen, if eligible, and should have received no more than 1 systemic regimen in the unresectable or metastatic setting.
HNSCC (closed to enrollment): Participants with HNSCC in Part C must have received prior therapy with a platinum-based regimen and/or a checkpoint inhibitor (CPI), if eligible, and must have experienced disease progression following such therapy. Participants should have received no more than 3 systemic lines of therapy in the recurrent or metastatic setting.
Part E

Participants with HNSCC must have experienced disease progression on or after their most recent systemic therapy. Participants should have received no more than 1 or 2 systemic lines of therapy in the recurrent/metastatic setting as specified below. Participants must have received a platinum-based regimen and a PD-(L)1 inhibitor.
Parts D, F, and G

Part D is closed to enrollment. Part F and Part G will enroll only participants with HNSCC.
Participants with HNSCC must have received no previous systemic therapy in the recurrent or metastatic disease setting.
Part D only

Participants with NSCLC must have histologically or cytologically documented squamous cell NSCLC and must have received no previous systemic therapy for metastatic disease or radiation therapy to the lung that is > 30 Gy within 6 months of the first dose of study treatment.
PD-L1 biomarker expression as determined by a PD-L1 IHC assay should be available
Part F only

Participants must have CPS ≥1 by local PD-L1 IHC assay to be eligible for enrollment. Participants must be able to submit a tissue sample for retrospective PD-L1 testing. Tissue may be fresh biopsy or archival, collected within 2 years of Cycle 1 Day 1.
Part G only

Non-EU eligibility criteria: No CPS requirement for the cohort evaluating tisotumab vedotin in combination with pembrolizumab and carboplatin.
EU-specific eligibility criteria: Participants must have a CPS ≥1 by local PD-L1 IHC assay.
Participants must be able to submit a tissue sample for retrospective PD-L1 testing. Tissue may be fresh biopsy or archival, collected within 2 years of Cycle 1 Day 1.
Baseline measurable disease as measured by RECIST v1. 1.
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.

Participants with primary neuroendocrine or sarcomatoid histologies. For HNSCC, participants may not have a primary site of nasopharynx or salivary gland.
Active bleeding conditions
Ocular surface disease at the time of enrollment (Note: cataract is not considered active ocular surface disease for this protocol)
Other cancer: known past or current malignancy other than inclusion diagnosis.
Uncontrolled tumor-related pain
Inflammatory lung disease. Participants with pulmonary disease are allowed if systemic steroids and long-term oxygen are not required
Peripheral neuropathy greater than or equal to Grade 2
Active brain metastasis
Ongoing clinically significant toxicity associated with prior treatment (including radiotherapy or surgery).
Part D, F, and G Only: Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Genmab
Merck Sharp & Dohme LLC

Investigators

STUDY_DIRECTOR: Pfizer CT.gov Call Center, Pfizer

Publications

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