Carcinoma, Non-Small-Cell Lung Clinical Trial
— innovaTV 207Official title:
Open Label Phase 2 Study of Tisotumab Vedotin for Locally Advanced or Metastatic Disease in 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.
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 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. |
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 | IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori- IRST S.r.l | Meldola FC | 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 | Duke University Medical Center | Durham | North Carolina |
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 | UC San Diego / Moores Cancer Center | La Jolla | California |
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 |
Lead Sponsor | Collaborator |
---|---|
Seagen Inc. | Genmab, Merck Sharp & Dohme LLC |
United States, Canada, France, Germany, Italy, Puerto Rico, Spain, United Kingdom,
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 3 years | |
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 3 years | |
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 3 years | |
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 |
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