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

Carcinoma, Non-Small-Cell Lung Clinical Trial

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Official title:

Open Label Phase 2 Study of Tisotumab Vedotin for Locally Advanced or Metastatic Disease in Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03485209
• Other study ID #: SGNTV-001
• Secondary ID: 2017-005076-26KE
• Status: Recruiting
• Phase: Phase 2
• Start date: June 25, 2018
• Est. completion date: November 30, 2026

Study information

• Verified date: April 2024
• Source: Seagen Inc.
• Contact: Seagen Trial Information Support
• Phone: 8663337436
• Email: clinicaltrials[@]seagen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial will study tisotumab vedotin to find out whether it is an effective treatment 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.

Description:

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 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 squamous cell carcinoma of the head and neck (SCCHN).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 692
• Est. completion date: November 30, 2026
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Parts A, B, and C
• Relapsed, locally-advanced or metastatic colorectal or pancreatic cancer, sqNSCLC, or SCCHN 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.
• SCCHN (closed to enrollment): Participants with SCCHN 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 SCCHN 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 SCCHN.
• Participants with SCCHN 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.

Exclusion Criteria:

• Participants with primary neuroendocrine or sarcomatoid histologies. For SCCHN, 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
• 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• tisotumab vedotin
Given into the vein (IV; intravenously)
• pembrolizumab
200mg or 400mg given by IV
• carboplatin
AUC 5mg/mL per minute or AUC 3.3mg/mL per minute given by IV
• cisplatin
100mg/m^2 given by IV

Locations

Country	Name	City	State
Canada	University of Alberta / Cross Cancer Institute	Edmonton	Alberta
France	Hospitalier Jean Minjoz	Besancon	Other
France	Centre léon Bérard	LYON cedex 08	Other
France	APHM Hôpital Nord	Marseille Cedex 20	Other
France	Hopital Prive du Confluent	Nantes Cedex 2	Other
France	Hopital Foch	Suresnes	Other
France	Institut Gustave Roussy	Villejuif Cedex	Other
Germany	Ruhr-Uni. Bochum, St. Josef-Hospital	Bochum	Other
Germany	Universitätsklinikum Halle-Universitätsklinik und Poliklinik	Halle	Other
Germany	Vincentius-Diakonissen-Kliniken gAG	Karlsruhe	Other
Italy	Azienda Ospedaliera Spedali Civili di Brescia	Brescia	Other
Italy	Azienda Ospedaliero Universitaria (AOU) Master Domin U.O. Oncologia Medica Traslazzionale	Catanzaro	Other
Italy	Istituto Europeo di Oncologia	Milano	Other
Italy	Seconda Università degli Studi di Napoli, AOU	Napoli	Other
Italy	Azienda USL Toscana Centro	Pistoia	Other
Italy	Oncologia Medica, Ospedale Civile S. Maria delle Croci	Ravenna	Other
Italy	PU Campus Bio-medico di Roma	Roma	Other
Puerto Rico	Pan American Center for Oncology Trials, LLC	Rio Piedras
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Other
Spain	Hospital Quironsalud Barcelona Instituto Oncologico Baselga	Barcelona	Other
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Other
Spain	HM Centro Integral Oncologico Clara Campal	Madrid	Other
Spain	Hospital Universitario Ramon y Cajal Servicio de Oncologia Medica Oficina de Ensayos Clinicos	Madrid	Other
Spain	Althaia Xarxa Assistencial Manresa	Manresa	Other
Spain	Son LLatzer University Hospital	Palma de Mallorca	Other
United Kingdom	Guys and St Thomas Hospital	London	Other
United States	University Cancer & Blood Center, LLC	Athens	Georgia
United States	Winship Cancer Institute / Emory University School of Medicine	Atlanta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	UNC Lineberger Comprehensive Cancer Center / University of North Carolina	Chapel Hill	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Texas Oncology - Fort Worth	Dallas	Texas
United States	Northwestern Medicine Cancer Center Kishwaukee / Kishwaukee Cancer Center	DeKalb	Illinois
United States	Karmanos Cancer Institute / Wayne State University	Detroit	Michigan
United States	University of Kansas Cancer Center	Fairway	Kansas
United States	Poudre Valley Health System (PVHS)	Fort Collins	Colorado
United States	Shands Cancer Center / University of Florida	Gainesville	Florida
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Ingalls Cancer Care / Ingalls Memorial Hospital	Harvey	Illinois
United States	MD Anderson Cancer Center / University of Texas	Houston	Texas
United States	Community Health Network	Indianapolis	Indiana
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Yale Cancer Center	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	University of Pennsylvania / Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	University of California Davis	Sacramento	California
United States	Washington University in St Louis	Saint Louis	Missouri
United States	HealthPartners Institute	Saint Louis Park	Minnesota
United States	Stanford Cancer Center / Blood and Marrow Transplant Program	San Jose	California
United States	Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Renovatio Clinical	The Woodlands	Texas
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Wake Forest Baptist Medical Center / Wake Forest University	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Seagen Inc.	Genmab, Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Puerto Rico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed Objective Response Rate (ORR) (Parts A, B, C, D, 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
Primary	Confirmed ORR per blinded independent central review (BICR) (Part E)	Proportion of patients who achieve a confirmed CR or PR according to RECIST v1.1 as assessed by BICR	Up to approximately 1 year
Secondary	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
Secondary	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
Secondary	Confirmed and Unconfirmed ORR per BICR (Part E)	Proportion of patients who achieve a CR or PR according to RECIST v1.1 as assessed by BICR	Up to approximately 1 year
Secondary	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
Secondary	DCR per BICR (Part E)	Proportion of patients who achieve a confirmed CR or PR according to RECIST v1.1 as assessed by BICR, 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 1 year
Secondary	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
Secondary	DOR per BICR (Part E)	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 BICR	Up to approximately 3 years
Secondary	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
Secondary	TTR per BICR (Part E)	Time from the start of study treatment to the first documentation of objective response, as assessed by BICR	Up to approximately 1 year
Secondary	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
Secondary	PFS per BICR (Part E)	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 BICR	Up to approximately 3 years
Secondary	Overall Survival (OS)	Time from the start of study treatment to date of death due to any cause	Up to approximately 4 years
Secondary	Cmax	Maximum observed plasma concentration	Through 30-37 days following the last dose; up to approximately 3 years
Secondary	Ctrough	Observed plasma concentration at the end of the dosing interval	Through 30-37 days following the last dose; up to approximately 3 years
Secondary	Incidence of anti-therapeutic antibodies (ATAs)		Through 30-37 days following the last dose; up to approximately 3 years