Clinical trial NCT03485209: Efficacy and Safety Study of Tisotumab Vedotin for Patients With Solid Tumors
Official title: Open Label Phase 2 Study of Tisotumab Vedotin for Locally Advanced or Metastatic Disease in Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Colorectal Neoplasms
Carcinoma, Non-Small-Cell Lung
Exocrine Pancreatic Cancer
Carcinoma, Squamous Cell of Head and Neck
Keywords: Colorectal cancer
NSCLC
sqNSCLC
CRC
Pancreatic cancer
Head and neck cancer
Seattle Genetics
HNSCC
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: Genmab
name: Merck Sharp & Dohme LLC
First posted: 2018-04-02
Enrollment: 352
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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 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).

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Confirmed Objective Response Rate (ORR) (Parts A, B, C, D, F, and G)
timeFrame: Up to approximately 3 years
measure: Confirmed ORR per blinded independent central review (BICR) (Part E)
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: Up to approximately 3 years
measure: Confirmed and Unconfirmed ORR
timeFrame: Up to approximately 3 years
measure: Confirmed and Unconfirmed ORR per BICR (Part E)
timeFrame: Up to approximately 3 years
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 3 years
measure: DCR per BICR (Part E)
timeFrame: Up to approximately 3 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 3 years
measure: DOR per BICR (Part E)
timeFrame: Up to approximately 3 years
measure: Time to Response (TTR)
timeFrame: Up to approximately 1 year
measure: TTR per BICR (Part E)
timeFrame: Up to approximately 1 year
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 3 years
measure: PFS per BICR (Part E)
timeFrame: Up to approximately 3 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 4 years
measure: Cmax
timeFrame: Through 30-37 days following the last dose; up to approximately 3 years
measure: Ctrough
timeFrame: Through 30-37 days following the last dose; up to approximately 3 years
measure: Incidence of anti-therapeutic antibodies (ATAs)
timeFrame: Through 30-37 days following the last dose; up to approximately 3 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego / Moores Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: San Jose
country: United States
facility: Stanford Cancer Center / Blood and Marrow Transplant Program
state: California
city: Fort Collins
country: United States
facility: Poudre Valley Health System (PVHS)
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Gainesville
country: United States
facility: Shands Cancer Center / University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute / Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: DeKalb
country: United States
facility: Northwestern Medicine Cancer Center Kishwaukee / Kishwaukee Cancer Center
state: Illinois
city: Geneva
country: United States
facility: Northwestern Medicine Cancer Center Delnor
state: Illinois
city: Harvey
country: United States
facility: Ingalls Cancer Care / Ingalls Memorial Hospital
state: Illinois
city: Warrenville
country: United States
facility: Northwestern Medicine Cancer Center Warrenville
state: Illinois
city: Indianapolis
country: United States
facility: Community Health Network
state: Indiana
city: Fairway
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute / Wayne State University
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis Park
country: United States
facility: HealthPartners Institute
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St Louis
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center / University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center / Wake Forest University
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania / Perelman Center for Advanced Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Texas Oncology - Fort Worth
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington
state: Washington
city: Edmonton
country: Canada
facility: University of Alberta / Cross Cancer Institute
state: Alberta
city: Besancon
country: France
facility: Hospitalier Jean Minjoz
state: Other
city: LYON cedex 08
country: France
facility: Centre léon Bérard
state: Other
city: Marseille Cedex 20
country: France
facility: APHM Hôpital Nord
state: Other
city: Nantes Cedex 2
country: France
facility: Hopital Prive du Confluent
state: Other
city: Suresnes
country: France
facility: Hopital Foch
state: Other
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
state: Other
city: Bochum
country: Germany
facility: Ruhr-Uni. Bochum, St. Josef-Hospital
state: Other
city: Halle
country: Germany
facility: Universitätsklinikum Halle-Universitätsklinik und Poliklinik
state: Other
city: Karlsruhe
country: Germany
facility: Vincentius-Diakonissen-Kliniken gAG
state: Other
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
state: Other
city: Catanzaro
country: Italy
facility: Azienda Ospedaliero Universitaria (AOU) Master Domin U.O. Oncologia Medica Traslazzionale
state: Other
city: Meldola FC
country: Italy
facility: IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori- IRST S.r.l
state: Other
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: Other
city: Napoli
country: Italy
facility: Seconda Università degli Studi di Napoli, AOU
state: Other
city: Pistoia
country: Italy
facility: Azienda USL Toscana Centro
state: Other
city: Ravenna
country: Italy
facility: Oncologia Medica, Ospedale Civile S. Maria delle Croci
state: Other
city: Roma
country: Italy
facility: PU Campus Bio-medico di Roma
state: Other
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Other
city: Barcelona
country: Spain
facility: Hospital Quironsalud Barcelona Instituto Oncologico Baselga
state: Other
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Other
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
state: Other
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
state: Other
city: Madrid
country: Spain
facility: HM Centro Integral Oncologico Clara Campal
state: Other
city: Manresa
country: Spain
facility: Althaia Xarxa Assistencial Manresa
state: Other
city: Palma de Mallorca
country: Spain
facility: Son LLatzer University Hospital
state: Other
city: London
country: United Kingdom
facility: Guys and St Thomas Hospital
state: Other
city: London
country: United Kingdom
facility: The Royal Marsden Hospital Chelsea
state: Other
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust (RM)
state: Other
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: