Clinical trial • Phase I/II • Oncology
DISITAMAB VEDOTIN for Breast cancer (HER2-positive and HER2-low) | Gastric cancer | Gastroesophageal junction adenocarcinoma | Oesophageal adenocarcinoma
Phase I/II trial of DISITAMAB VEDOTIN for Breast cancer (HER2-positive and HER2-low) | Gastric cancer | Gastroesophageal junction adenocarcinoma | Oesopha…
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Breast cancer (HER2-positive and HER2-low) | Gastric cancer | Gastroesophageal junction adenocarcinoma | Oesophageal adenocarcinoma
- Trial Stage
- Phase I/II
- Drug Modality
- ADC|Small molecule
Key dates
- Initial CTIS Submission Date
- 15-02-2024
- First CTIS Authorization Date
- 10-06-2024
Trial design
open-label, none/not specified-controlled, adaptive Phase I/II trial in Germany, Italy, Spain and others.
- Open Label
- Yes
- Comparator
- None/Not specified
- Adaptive
- True, Dose-escalation design to identify the maximum tolerated dose (MTD) and/or optimal dose; no further adaptive rules, interim analysis plans or stopping rules are described in the CTIS metadata.
- Biomarker Stratified
- True, biomarker: HER2 (strata: HER2-low defined as IHC 1+ or IHC 2+/ISH-negative; HER2-positive defined as IHC 3+ or IHC 2+/ISH+)
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 126
Eligibility
Recruits 126 Vulnerable population selected (isVulnerablePopulationSelected = true). No further details on consent/assent handling or specific vulnerable-group procedures are provided in the CTIS record or the available metadata..
- Vulnerable Population
- Vulnerable population selected (isVulnerablePopulationSelected = true). No further details on consent/assent handling or specific vulnerable-group procedures are provided in the CTIS record or the available metadata.
Inclusion criteria
- {"criterion_text":"- Histologically or cytologically confirmed diagnosis of breast carcinoma or gastric or gastroesophageal junction adenocarcinoma\n- HER2-low status determined by most recent local assessment (IHC 1+ or IHC 2+/in situ hybridization (ISH)-negative) based on American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) guidelines for assessment of HER2 in BC for interpretation of HER2 expression and amplification or must have HER2-low expression defined as IHC 1+ or IHC 2+/ISH-negative determined by most recent local assessment based off the ASCO and CAP guidelines for assessment of HER2 in gastric cancer (GC) for interpretation of HER2 expression and amplification. -or-\n- HER2+ status determined by most recent local assessment (IHC 3+ or IHC 2+/ISH+) according to ASCO and CAP guidelines for assessment of HER2 in BC or GC/GEJC\n- Prior therapies requirements: In HER2-Low Breast Cancer participants: a. No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC. Participants previously treated with (neo)adjuvant cytotoxic chemotherapy and have disease relapsed within 6 month of treatment is considered to have received 1 line of cytotoxic therapy for LA/mBC. b. Participants with known germline BRCA mutation must have received a PARP-inhibitor, where available and not medically contraindicated c. Have progression on or after, or be intolerant to, trastuzumab deruxtecan (T-DXd) d. Participants with hormone receptor-positive (HR+) tumors must have intolerance to endocrine therapy or endocrine therapy refractory disease: i. Progressed on ≥2 lines of endocrine therapy for LA/mBC AND had received a CDK4/6 inhibitor in the adjuvant or metastatic setting if available as local standard of care and not contraindicated OR ii. Progressed on 1 line of endocrine therapy for LA/mBC AND had a relapse while on adjuvant endocrine therapy after definitive surgery for primary tumor AND had received a CDK4/6 inhibitor in the adjuvant or advanced setting if available as local standard of care and not contraindicated iii. Note that prior endocrine and CDK4/6 inhibitor therapy for low ER and PR expression (immunohistochemical staining of only 1 to 10% of tumor cells) is per institutional standard and not mandated prior to enrollment iv. Participants with HR+ HER2-low tumors must have progression on or after, or be intolerant to, prior cytotoxic chemotherapy (including ADCs) if available as local standard of care for endocrine therapy refractory advanced disease. e. Participants with hormone receptor (HR) negative, HER2-low and programmed cell death receptor ligand 1 (PD-L1)-positive tumors must have received pembrolizumab (or other PD-(L)1 inhibitor) with chemotherapy if available as local standard of care therapy and not medically contraindicated. In HER2+ Breast Cancer participants: a. Received first line standard of care therapy for advanced disease (e.g. trastuzumab, pertuzumab and a taxane or T-DXd based therapy). b. Have progression on or after, or be intolerant to, T-DXd c. No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC\n- All participants in: HER2-Low Gastric or Gastroesophageal Junction Adenocarcinoma must have: a. Prior systemic therapy with platinum, fluorouracil, or taxane for locally advanced unresectable or metastatic disease b. Progression within 6 months of last dose of (neo)adjuvant cytotoxic chemotherapy is considered as 1 line of systemic therapy for LA/mGC/GEJC c. Prior anti-PD-(L)1 (programmed cell death receptor 1 [PD1] and PD-L1, collectively) therapy is allowed d. No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADC) for LA/mGC/GEJC HER2+ LA/m Gastric or Gastroesophageal Junction Adenocarcinoma must have: a. Received prior trastuzumab plus fluoropyrimidine and platinum containing chemotherapy if no contraindication. b. Prior T-DXd treatment is allowed c. Prior PD1 inhibitor therapy is allowed d. No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mGC/GEJC.\n- Note that gastric cancer cohorts are closed for enrollment. There are no LA/mGC/GEJC participants in the dose optimization and expansion phases."}
Exclusion criteria
- {"criterion_text":"- Known hypersensitivity to any excipient contained in the drug formulation of disitamab vedotin or tucatinib\n- Prior therapy with ADCs with MMAE payload\n- Prior therapy with tucatinib\n- Participants who have received prior systemic anticancer treatment including investigational agents within 4 weeks, or 5 half-lives, whichever is shorter, prior to first dose of study treatment.\n- Participants with a history of other invasive malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.\n- Participants who have received prior radiotherapy within 2 weeks of start of study treatment"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Incidence of dose-limiting toxicities (DLTs) in dose escalation phase","definition_or_measurement_approach":"Assessment of DLTs during the dose escalation phase (safety/tolerability endpoint)"}
- {"endpoint_text":"- Type, incidence, severity, seriousness, and relatedness of AEs","definition_or_measurement_approach":"Adverse events characterized by type, incidence, severity, seriousness and relatedness (standard safety AE collection; investigator assessment)"}
- {"endpoint_text":"- Type, incidence, and severity of laboratory abnormalities as well as significant changes from baseline","definition_or_measurement_approach":"Laboratory abnormalities evaluated for type, incidence, severity and significant changes from baseline (laboratory monitoring)"}
- {"endpoint_text":"- Frequency of treatment interruptions, dose reductions, and treatment discontinuations due to AEs","definition_or_measurement_approach":"Reporting frequency of treatment interruptions, dose reductions, and discontinuations attributable to adverse events"}
- {"endpoint_text":"- ORR (confirmed complete response [CR] and confirmed partial response [PR]) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessment","definition_or_measurement_approach":"Objective response rate assessed per RECIST v1.1 by investigator (confirmed CR and PR)"}
Secondary endpoints
- {"endpoint_text":"- Duration of response (DOR) per RECIST v1.1 by investigator assessment","definition_or_measurement_approach":"DOR evaluated per RECIST v1.1 by investigator"}
- {"endpoint_text":"- Disease control rate (DCR) (confirmed CR, confirmed PR, and stable disease) per RECIST v1.1 by investigator assessment","definition_or_measurement_approach":"DCR (confirmed CR, PR, and stable disease) per RECIST v1.1 by investigator"}
- {"endpoint_text":"- Progression-free survival (PFS) per RECIST v1.1 by investigator assessment","definition_or_measurement_approach":"PFS determined per RECIST v1.1 by investigator assessment"}
- {"endpoint_text":"- Overall Survival (OS)","definition_or_measurement_approach":"Overall survival (time from defined baseline to death from any cause)"}
- {"endpoint_text":"- Estimates of selected PK parameters of disitamab vedotin, total antibody, and unconjugated MMAE","definition_or_measurement_approach":"Pharmacokinetic parameter estimation for disitamab vedotin, total antibody, and unconjugated MMAE"}
- {"endpoint_text":"- Incidence of anti-drug antibodies (ADA) against disitamab vedotin","definition_or_measurement_approach":"Immunogenicity assessment: incidence of ADA against disitamab vedotin"}
Recruitment
- Planned Sample Size
- 126
- Recruitment Window Months
- 64
- Consent Approach
- Informed consent is required; subject information and informed consent form documents are present in multiple languages (DE, ES, IT). No detailed text about assent, age-specific consent procedures, or specific consenting personnel is provided in the CTIS metadata.
Geography
- Total Number Of Sites
- 22
- Total Number Of Participants
- 68
Germany
- Earliest CTIS Part Ii Submission Date
- 15-04-2024
- Latest Decision Or Authorization Date
- 16-04-2025
- Processing Time Days
- 366
- Number Of Sites
- 4
- Number Of Participants
- 18
Sites
- Site Name
- Universitaetsklinikum Heidelberg AöR
- Department Name
- Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
- Principal Investigator Name
- Andreas Schneeweiss
- Principal Investigator Email
- andreas.schneeweiss@med.uni-heidelberg.de
- Contact Person Name
- Andreas Schneeweiss
- Contact Person Email
- andreas.schneeweiss@med.uni-heidelberg.de
- Site Name
- Universitaetsklinikum Essen AöR
- Department Name
- Innere Klinik (Tumorforschung) Westdeutsches Tumorzentrum
- Principal Investigator Name
- Anja Welt
- Principal Investigator Email
- anja.welt@uk-essen.de
- Contact Person Name
- Anja Welt
- Contact Person Email
- anja.welt@uk-essen.de
- Site Name
- Charite Research Organisation GmbH
- Department Name
- Medizinische Klinik mit Schwerpunkt Haematologie, Onkologie und Tumorimmunologie (CBF)
- Principal Investigator Name
- Antonia Busse
- Principal Investigator Email
- antonia.busse@charite.de
- Contact Person Name
- Antonia Busse
- Contact Person Email
- antonia.busse@charite.de
- Site Name
- Klinikum rechts der Isar der TU Muenchen AöR
- Department Name
- Klinik unnd Poliklinik für Innere Medizin III, Haematologie und Onkologie
- Principal Investigator Name
- Sylvie Lorenzen
- Principal Investigator Email
- sylvie.lorenzen@mri.tum.de
- Contact Person Name
- Sylvie Lorenzen
- Contact Person Email
- sylvie.lorenzen@mri.tum.de
Italy
- Earliest CTIS Part Ii Submission Date
- 24-04-2024
- Latest Decision Or Authorization Date
- 29-04-2026
- Processing Time Days
- 735
- Number Of Sites
- 7
- Number Of Participants
- 18
Sites
- Site Name
- Centro Ricerche Cliniche Di Verona S.r.l.
- Department Name
- Medical Oncology
- Principal Investigator Name
- Camilla Zecchetto
- Principal Investigator Email
- camilla.zecchetto@aovr.veneto.it
- Contact Person Name
- Camilla Zecchetto
- Contact Person Email
- camilla.zecchetto@aovr.veneto.it
- Site Name
- IRCCS Istituto Nazionale Tumori Fondazione Pascale
- Department Name
- Medical Oncology
- Principal Investigator Name
- Michelino DeLaurentiis
- Principal Investigator Email
- m.delaurentiiis@istitutotumori.na.it
- Contact Person Name
- Michelino DeLaurentiis
- Contact Person Email
- m.delaurentiiis@istitutotumori.na.it
- Site Name
- Humanitas Istituto Clinico Catanese S.p.A.
- Department Name
- Medical Oncology
- Principal Investigator Name
- Maria Vita Sano'
- Principal Investigator Email
- Maria_vita.sano@humanitascatania.it
- Contact Person Name
- Maria Vita Sano'
- Contact Person Email
- Maria_vita.sano@humanitascatania.it
- Site Name
- ASST Grande Ospedale Metropolitano Niguarda
- Department Name
- Medical Oncology
- Principal Investigator Name
- Salvatore Siena
- Principal Investigator Email
- salvatore.siena@ospedaleniguarda.it
- Contact Person Name
- Salvatore Siena
- Contact Person Email
- salvatore.siena@ospedaleniguarda.it
- Site Name
- European Institute Of Oncology S.r.l.
- Department Name
- Medical Oncology
- Principal Investigator Name
- Giuseppe Curigliano
- Principal Investigator Email
- Giuseppe.curigliano@ieo.it
- Contact Person Name
- Giuseppe Curigliano
- Contact Person Email
- Giuseppe.curigliano@ieo.it
- Site Name
- Universita' Degli Studi Di Napoli Federico II
- Department Name
- Medical Oncology
- Principal Investigator Name
- Roberto Bianco
- Principal Investigator Email
- robianco@unina.it
- Contact Person Name
- Roberto Bianco
- Contact Person Email
- robianco@unina.it
- Site Name
- Centro Ricerche Cliniche Di Verona S.r.l.
- Department Name
- Medical Oncology
- Principal Investigator Name
- Camilla Zecchetto
- Principal Investigator Email
- camilla.zecchetto@aovr.veneto.it
- Contact Person Name
- Camilla Zecchetto
- Contact Person Email
- camilla.zecchetto@aovr.veneto.it
Spain
- Earliest CTIS Part Ii Submission Date
- 27-05-2024
- Latest Decision Or Authorization Date
- 08-05-2026
- Processing Time Days
- 711
- Number Of Sites
- 6
- Number Of Participants
- 16
Sites
- Site Name
- Hospital Universitario Basurto
- Department Name
- Oncology
- Principal Investigator Name
- Elena Galve Calvo
- Principal Investigator Email
- elena.galvecalvo@osakidetza.eus
- Contact Person Name
- Elena Galve Calvo
- Contact Person Email
- elena.galvecalvo@osakidetza.eus
- Site Name
- Hospital Universitario Hm Sanchinarro
- Department Name
- Oncology
- Principal Investigator Name
- Ramon Yarza
- Principal Investigator Email
- Ramon.yarza@startmadrid.com
- Contact Person Name
- Ramon Yarza
- Contact Person Email
- Ramon.yarza@startmadrid.com
- Site Name
- Institut Catala D'oncologia
- Department Name
- Oncology
- Principal Investigator Name
- Agostina Stardella
- Principal Investigator Email
- astradella@idibell.cat
- Contact Person Name
- Agostina Stardella
- Contact Person Email
- astradella@idibell.cat
- Site Name
- Vall D'hebron Institut De Recerca
- Department Name
- Oncology
- Principal Investigator Name
- Cristina Saura Manich
- Principal Investigator Email
- csaura@vhio.net
- Contact Person Name
- Cristina Saura Manich
- Contact Person Email
- csaura@vhio.net
- Site Name
- Hospital Clinico Universitario De Valencia
- Department Name
- Oncology
- Principal Investigator Name
- Andres Cervantes Ruiperez
- Principal Investigator Email
- andres.cervantes@uv.es
- Contact Person Name
- Andres Cervantes Ruiperez
- Contact Person Email
- andres.cervantes@uv.es
- Site Name
- Hospital Universitario Basurto
- Department Name
- Oncology
- Principal Investigator Name
- Elena Galve Calvo
- Principal Investigator Email
- elena.galvecalvo@osakidetza.eus
- Contact Person Name
- Elena Galve Calvo
- Contact Person Email
- elena.galvecalvo@osakidetza.eus
France
- Earliest CTIS Part Ii Submission Date
- 30-05-2024
- Latest Decision Or Authorization Date
- 17-06-2024
- Processing Time Days
- 18
- Number Of Sites
- 5
- Number Of Participants
- 16
Sites
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Medical Oncology
- Principal Investigator Name
- Aurore Vozy
- Principal Investigator Email
- aurore.vozy@aphp.fr
- Contact Person Name
- Aurore Vozy
- Contact Person Email
- aurore.vozy@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Poitiers
- Department Name
- Medical Oncology
- Principal Investigator Name
- Nicolas Isambert
- Principal Investigator Email
- nicolas.isambert@chu-poitiers.fr
- Contact Person Name
- Nicolas Isambert
- Contact Person Email
- nicolas.isambert@chu-poitiers.fr
- Site Name
- Centre Hospitalier Regional Et Universitaire De Brest
- Department Name
- Medical Oncology
- Principal Investigator Name
- Jean-Philippe Metges
- Principal Investigator Email
- jean-philippe.metges@chu-brest.fr
- Contact Person Name
- Jean-Philippe Metges
- Contact Person Email
- jean-philippe.metges@chu-brest.fr
- Site Name
- Institut Paoli Calmettes
- Department Name
- Medical Oncology
- Principal Investigator Name
- Cécile Vicier
- Principal Investigator Email
- vicierc@ipc.unicancer.fr
- Contact Person Name
- Cécile Vicier
- Contact Person Email
- vicierc@ipc.unicancer.fr
- Site Name
- Institut De Cancerologie De Lorraine
- Department Name
- Medical Oncology
- Principal Investigator Name
- Aurélien Lambert
- Principal Investigator Email
- a.lambert@nancy.unicancer.fr
- Contact Person Name
- Aurélien Lambert
- Contact Person Email
- a.lambert@nancy.unicancer.fr
Sponsor
Primary sponsor
- Full Name
- Seagen Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Icon Clinical Research Limited
- Responsibilities
- Patient Non-Advocacy; Independent Central Radiology (collection and hold of images); multiple sponsor support functions (various sponsorDuties entries)
- Name
- 4g Clinical LLC
- Responsibilities
- Duties listed under sponsorDuties (codes 14 and 3) — specific responsibilities not further detailed in metadata
- Name
- WCG Clinical Inc.
- Responsibilities
- Duties listed under sponsorDuties (codes 12 and 2) — specific responsibilities not further detailed in metadata
- Name
- Scout Clinical
- Responsibilities
- Patient Reimbursement (listed duty)
Third parties
- {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Provides lab kits and receives/stores exploratory specimens","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Roles with codes 6 and 7 (specific duties not detailed in metadata)","organisation_type":"Non-Pharmaceutical company"}
- {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Patient Non-Advocacy; other site/sponsor support functions (code 15 indicated in one entry); multiple listings with various responsibilities","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Q2 Solutions LLC","duties_or_roles":"Sponsor duty code 4 (specific duty not detailed in metadata)","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Independent Central Radiology: collection and hold of images.","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"Sponsor duties with codes 14 and 3 (specific duties not detailed in metadata)","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Cellcarta Naperville LLC","duties_or_roles":"Sponsor duty code 4 (specific duty not detailed in metadata)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Sponsor duties with codes 12 and 2 (specific duties not detailed in metadata)","organisation_type":"Pharmaceutical company"}
- {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Multiple sponsor duties including codes 1,11,12,5,8 (specific duties not detailed in metadata)","organisation_type":"Pharmaceutical company"}
- {"country":"Switzerland","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Sponsor duty code 14 (specific duty not detailed in metadata)","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Disitamab Vedotin
- Active Substance
- DISITAMAB VEDOTIN
- Modality
- ADC
- Routes Of Administration
- IV INFUSION
- Route
- IV infusion
- Authorisation Status
- Investigational (prodAuthStatus=1)
- Investigational Product Name
- TUKYSA 150 mg film-coated tablets
- Active Substance
- TUCATINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- Oral
- Authorisation Status
- Authorised (marketing authorisation information present, prodAuthStatus=2)
- Dose Levels
- 150 mg (product strengths listed: 150 mg and 50 mg)
- Investigational Product Name
- TUKYSA 50 mg film-coated tablets
- Active Substance
- TUCATINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- Oral
- Authorisation Status
- Authorised (marketing authorisation information present, prodAuthStatus=2)
- Dose Levels
- 50 mg (product strengths listed: 150 mg and 50 mg)
- Combination Treatment
- Yes
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