Clinical trial • Phase III • Oncology

TRASTUZUMAB DERUXTECAN for Non-small cell lung cancer with HER2 exon 19 or 20 mutations

Phase III trial of TRASTUZUMAB DERUXTECAN for Non-small cell lung cancer with HER2 exon 19 or 20 mutations.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Non-small cell lung cancer with HER2 exon 19 or 20 mutations
Trial Stage
Phase III
Drug Modality
ADC|Monoclonal antibody|Small molecule

Key dates

Initial CTIS Submission Date
13-06-2024
First CTIS Authorization Date
11-07-2024

Trial design

Randomised, open-label, cisplatin or carboplatin with pemetrexed and pembrolizumab (platinum doublet chemotherapy with pemetrexed plus pembrolizumab); dosing and schedule not specified in ctis record.-controlled Phase III trial in Denmark, Germany, France and others.

Randomised
Yes
Open Label
Yes
Comparator
Cisplatin or carboplatin with pemetrexed and pembrolizumab (platinum doublet chemotherapy with pemetrexed plus pembrolizumab); dosing and schedule not specified in CTIS record.
Target Sample Size
290

Eligibility

Recruits 290 Vulnerable population selected. Informed consent obtained via subject information and informed consent forms. Country-specific ICFs and participant documents are provided (including adult ICFs and specific ICFs for pregnant partners, genetic research, pre-screening and future research) in multiple country/language versions..

Vulnerable Population
Vulnerable population selected. Informed consent obtained via subject information and informed consent forms. Country-specific ICFs and participant documents are provided (including adult ICFs and specific ICFs for pregnant partners, genetic research, pre-screening and future research) in multiple country/language versions.

Inclusion criteria

  • {"criterion_text":"- Male and female participants at least 18 years of age\n- Locally advanced not amenable to curative therapy, or metastatic disease\n- Histologically documented non-squamous NSCLC with HER2 mutation in exons 19 or 20 by tissue NGS or ctDNA (locally or centrally tested)\n- Treatment-naïve for palliative intent systemic therapy for locally advanced or metastatic disease\n- Left ventricular ejection fraction (LVEF) ≥ 50%\n- Measurable disease assessed by Investigator based on RECIST v1.1\n- Protocol-defined adequate organ function including cardiac, renal, hepatic function\n- ECOG 0-1\n- Having tumour tissue available for central testing"}

Exclusion criteria

  • {"criterion_text":"- Tumors with targetable alterations to EGFR (or other targetable mutations including but not limited to ALK, if routinely tested as a targetable alteration with approved available therapy)\n- Clinically active brain metastases, defined as untreated AND/OR symptomatic, or requiring therapy to control associated symptoms. All participants with brain metastases must have previously completed local therapy.\n- Active autoimmune or inflammatory disorders\n- Medical history of myocardial infarction within 6 months prior to randomization\n- History of non-infectious pneumonitis/ILD, current or suspected ILD\n- Lung-specific intercurrent clinical significant severe illness\n- Contraindication to platinum-based doublet chemotherapy or pembrolizumab"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Progression Free Survival (PFS) defined as time from randomization until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR) or death due to any cause.","definition_or_measurement_approach":"PFS defined as time from randomization until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR) or death due to any cause."}

Secondary endpoints

  • {"endpoint_text":"- 1. Overall Survival (OS) defined as time from randomization until date of death due to any cause.","definition_or_measurement_approach":"OS defined as time from randomization until date of death due to any cause."}
  • {"endpoint_text":"- 2-1: PFS by investigator assessment defined as time from randomization until progression as assessed by investigator (per RECIST 1.1) or death due to any cause. Objective Response Rate (ORR) and Duration of Response (DoR) by BICR and Investigator assessment per RECIST 1.1. ORR is defined as proportion of participants who have a complete response (CR) or partial response (PR).","definition_or_measurement_approach":"PFS by investigator per RECIST 1.1; ORR defined as proportion with CR or PR; DoR measured by time from first documented response to progression. Assessed by BICR and investigator."}
  • {"endpoint_text":"- 2-2: DoR is defined as time from date of first documented response until date of documented progression. PFS2 is defined as time from randomization to second progression on next-line of treatment as assessed by investigator or death due to any cause.","definition_or_measurement_approach":"DoR: time from first documented response to documented progression. PFS2: time from randomization to second progression on next-line treatment or death; investigator-assessed."}
  • {"endpoint_text":"- 2-3: PFS12 is the landmark of PFS which is defined as proportion of participants alive and progression-free at 12 months as assessed by BICR and investigator. OS24 is the landmark of OS defined as proportion of patients alive at 24 months","definition_or_measurement_approach":"PFS12: proportion alive and progression-free at 12 months by BICR and investigator; OS24: proportion alive at 24 months."}
  • {"endpoint_text":"- 3. CNS-PFS defined as time from randomization until CNS-progression (RECIST 1.1) as assessed by BICR or death due to any cause in absence of CNS progression.","definition_or_measurement_approach":"CNS-PFS: time from randomization to CNS progression per RECIST 1.1 by BICR or death absent CNS progression."}
  • {"endpoint_text":"- 4. AEs, SAEs, changes from baseline in laboratory parameters, vital signs, ECG, ECHO/MUGA results.","definition_or_measurement_approach":"Safety and tolerability assessed via adverse events (AEs), serious adverse events (SAEs), lab parameter changes, vital signs, ECG, and ECHO/MUGA."}
  • {"endpoint_text":"- 5. Pharmacokinetics (PK) of T-DXd and serum concentration of T-DXd, total anti-HER2 antibody and DXd","definition_or_measurement_approach":"PK measures of T-DXd and serum concentrations of T-DXd, total anti-HER2 antibody and DXd."}
  • {"endpoint_text":"- 6. Presence of ADAs for T-DXd","definition_or_measurement_approach":"Assessment of anti-drug antibodies (ADAs) for T-DXd in serum."}
  • {"endpoint_text":"- 7. Time to sustained deterioration in pulmonary symptoms while on treatment using NSCLC-Symptom Assessment Questionnaire (SAQ)","definition_or_measurement_approach":"Time to sustained deterioration measured by NSCLC-SAQ patient-reported outcomes."}
  • {"endpoint_text":"- 8. Patient Reported Tolerability will be described among participants using the following outcomes: Symptomatic AEs (assessed by PROCTCAE and EORTC Item Library), Overall Side Effect Bother (reported on Patient's Global Impression of Treatment Tolerability (PGI-TT)), Physical Function (based on EORTC-QLQ-30)","definition_or_measurement_approach":"Patient-reported tolerability assessed via PRO-CTCAE, EORTC Item Library, PGI-TT, and EORTC-QLQ-30 physical function scores."}

Recruitment

Planned Sample Size
290
Recruitment Window Months
33
Consent Approach
Informed consent obtained from adult participants (≥18) via subject information and informed consent forms. Country-specific ICFs are provided in multiple languages and for specific situations (e.g., pregnant partner ICF, genetic research, pre-screening, optional future research).

Geography

Total Number Of Sites
38
Total Number Of Participants
160

Denmark

Earliest CTIS Part Ii Submission Date
26-06-2024
Latest Decision Or Authorization Date
13-02-2026
Processing Time Days
597
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
Lillebaelt Hospital
Department Name
Onkologis Afdeling
Principal Investigator Name
Christa Nyhus
Principal Investigator Email
Christa.Haugaard.Nyhus@rsyd.dk
Contact Person Name
Christa Nyhus
Contact Person Email
Christa.Haugaard.Nyhus@rsyd.dk

Germany

Earliest CTIS Part Ii Submission Date
26-06-2024
Latest Decision Or Authorization Date
18-02-2026
Processing Time Days
602
Number Of Sites
5
Number Of Participants
9

Sites

Site Name
Ludwig-Maximilians-Universitaet Muenchen
Department Name
Med. V, Pneumologie
Principal Investigator Name
Amanda Tufman
Principal Investigator Email
amanda.tufman@med.uni-muenchen.de
Contact Person Name
Amanda Tufman
Site Name
University Hospital Cologne AöR
Department Name
Centrum für integrierte Onkologie
Principal Investigator Name
Matthias Scheffler
Principal Investigator Email
Matthias.scheffler@uk-koeln.de
Contact Person Name
Matthias Scheffler
Contact Person Email
Matthias.scheffler@uk-koeln.de
Site Name
Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
Department Name
Medizinische Klinik und Poliklinik I
Principal Investigator Name
Martin Wermke
Principal Investigator Email
martin.wermke@uniklinikum-dresden.de
Contact Person Name
Martin Wermke
Site Name
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Department Name
III. Medizinische Klinik und Poliklinik
Principal Investigator Name
Juergen Alt
Principal Investigator Email
juergen.alt@unimedizin-mainz.de
Contact Person Name
Juergen Alt
Site Name
Pius-Hospital Oldenburg
Department Name
Internistische Onkologie
Principal Investigator Name
Frank Griessinger
Principal Investigator Email
frank.griesinger@pius-hospital.de
Contact Person Name
Frank Griessinger

France

Earliest CTIS Part Ii Submission Date
26-06-2024
Latest Decision Or Authorization Date
18-02-2026
Processing Time Days
602
Number Of Sites
8
Number Of Participants
36

Sites

Site Name
CHU De Bordeauxt
Department Name
Département d'oncologie médicale
Principal Investigator Name
Charlotte Domblides
Principal Investigator Email
charlotte.domblides@chu-bordeaux.fr
Contact Person Name
Charlotte Domblides
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Service oncologie multidisciplinaire et innovations thérapeutiques
Principal Investigator Name
Pascale Tomasini
Principal Investigator Email
pascale.tomasini@ap-hm.fr
Contact Person Name
Pascale Tomasini
Contact Person Email
pascale.tomasini@ap-hm.fr
Site Name
Institut Gustave Roussy
Department Name
Département d'oncologie médicale - Groupe Thoracique
Principal Investigator Name
David Planchard
Principal Investigator Email
david.planchard@gustaveroussy.fr
Contact Person Name
David Planchard
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Service oncologie thoracique
Principal Investigator Name
Elvire Pons
Principal Investigator Email
elvire.pons@chu-nantes.fr
Contact Person Name
Elvire Pons
Contact Person Email
elvire.pons@chu-nantes.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Service de Pneumologie
Principal Investigator Name
Julien Mazières
Principal Investigator Email
mazieres.j@chu-toulouse.fr
Contact Person Name
Julien Mazières
Contact Person Email
mazieres.j@chu-toulouse.fr
Site Name
Centre Leon Berard
Department Name
Service d'oncologie médicale - oncologie thoracique
Principal Investigator Name
Maurice Perol
Principal Investigator Email
maurice.perol@lyon.unicancer.fr
Contact Person Name
Maurice Perol
Site Name
Centr Georges Francois Leclerc
Department Name
Département d'oncologie médicale
Principal Investigator Name
Laure Favier
Principal Investigator Email
lfavier@cgfl.fr
Contact Person Name
Laure Favier
Contact Person Email
lfavier@cgfl.fr
Site Name
Centre Hospitalier Le Mans
Department Name
Pneumologie et Oncologie Thoracique
Principal Investigator Name
Olivier Molinier
Principal Investigator Email
o.molinier@ch-lemans.fr
Contact Person Name
Olivier Molinier
Contact Person Email
o.molinier@ch-lemans.fr

Austria

Earliest CTIS Part Ii Submission Date
26-06-2024
Latest Decision Or Authorization Date
17-02-2026
Processing Time Days
601
Number Of Sites
3
Number Of Participants
9

Sites

Site Name
Medizinische Universitaet Innsbruck
Department Name
Univ.-Klinik für Innere Medizin V
Principal Investigator Name
Andreas Pircher
Principal Investigator Email
Andreas.pircher@tirol-kliniken.at
Contact Person Name
Andreas Pircher
Site Name
Ordensklinikum Linz GmbH
Department Name
Servicestelle für klinische Studien Pneumologie 2, 2B
Principal Investigator Name
Michael Schumacher
Principal Investigator Email
michael.schumacher@ordensklinikum.at
Contact Person Name
Michael Schumacher
Site Name
Stadt Wien Wiener Gesundheitsverbund
Department Name
Abteilung für Innere Medizin und Pneumologie
Principal Investigator Name
Maximilian Hochmair
Principal Investigator Email
maximilian.hochmair@gesundheitsverbund.at
Contact Person Name
Maximilian Hochmair

Spain

Earliest CTIS Part Ii Submission Date
26-06-2024
Latest Decision Or Authorization Date
17-02-2026
Processing Time Days
601
Number Of Sites
4
Number Of Participants
26

Sites

Site Name
Hospital Universitario 12 De Octubre
Department Name
Servicio de Oncologia
Principal Investigator Name
Luis Paz-Ares Rodriguez
Principal Investigator Email
lpazaresr@seom.org
Contact Person Name
Luis Paz-Ares Rodriguez
Contact Person Email
lpazaresr@seom.org
Site Name
Hospital Universitario Regional De Malaga
Department Name
Servicio de Oncologia
Principal Investigator Name
Alexandra Cantero Gonzalez
Principal Investigator Email
alexandra.cantero@uma.es
Contact Person Name
Alexandra Cantero Gonzalez
Contact Person Email
alexandra.cantero@uma.es
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Servicio de Oncologia
Principal Investigator Name
Oscar Juan Vidal
Principal Investigator Email
juan_osc@gva.es
Contact Person Name
Oscar Juan Vidal
Contact Person Email
juan_osc@gva.es
Site Name
Institut Catala D'oncologia
Department Name
Servicio de Oncologia
Principal Investigator Name
Ernest Nadal Alforja
Principal Investigator Email
esnadal@iconcologia.net
Contact Person Name
Ernest Nadal Alforja
Contact Person Email
esnadal@iconcologia.net

Poland

Earliest CTIS Part Ii Submission Date
26-06-2024
Latest Decision Or Authorization Date
16-02-2026
Processing Time Days
600
Number Of Sites
5
Number Of Participants
3

Sites

Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Klinika Nowotworów Pluca i Klatki Piersiowej
Principal Investigator Name
Dariusz Kowalski
Principal Investigator Email
dariusz.kowalski@nio.gov.pl
Contact Person Name
Dariusz Kowalski
Contact Person Email
dariusz.kowalski@nio.gov.pl
Site Name
Wojewodzki Szpital Im. Sw.Ojca Pio W Przemyslu
Department Name
Oddzial Onkologiczny z Pododdziałem Dziennej Chemioterapii
Principal Investigator Name
Kamil Kuc
Principal Investigator Email
kkuc@wszp.pl
Contact Person Name
Kamil Kuc
Contact Person Email
kkuc@wszp.pl
Site Name
Centrum Pulmonologii I Torakochirurgii W Bystrej
Department Name
Oddzial Pulmonologiczno-Onkologiczny z Chemioterapia
Principal Investigator Name
Adrianna Gega-Czarnota
Principal Investigator Email
Adrianna.gega@gmail.com
Contact Person Name
Adrianna Gega-Czarnota
Contact Person Email
Adrianna.gega@gmail.com
Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
Klinika Onkologii i Radioterapii
Principal Investigator Name
Rafal Dziadziuszko
Principal Investigator Email
rafald@gumed.edu.pl
Contact Person Name
Rafal Dziadziuszko
Contact Person Email
rafald@gumed.edu.pl
Site Name
Warminsko-Mazurskie Centrum Chorob Pluc W Olsztynie
Department Name
Oddzial Onkologii z Pododdziałem Chemioterapii
Principal Investigator Name
Jarosław Kolb-Sielecki
Principal Investigator Email
j.kolbsielecki@gmail.com
Contact Person Name
Jarosław Kolb-Sielecki
Contact Person Email
j.kolbsielecki@gmail.com

Belgium

Earliest CTIS Part Ii Submission Date
26-06-2024
Latest Decision Or Authorization Date
16-02-2026
Processing Time Days
600
Number Of Sites
3
Number Of Participants
9

Sites

Site Name
Universitair Ziekenhuis Gent
Department Name
Pneumology
Principal Investigator Name
Veerle Surmont
Principal Investigator Email
veerle.surmont@uzgent.be
Contact Person Name
Veerle Surmont
Contact Person Email
veerle.surmont@uzgent.be
Site Name
Jessa Ziekenhuis
Department Name
Pneumology
Principal Investigator Name
Kristof Cuppens
Principal Investigator Email
Kristof.Cuppens@jessazh.be
Contact Person Name
Kristof Cuppens
Contact Person Email
Kristof.Cuppens@jessazh.be
Site Name
UZ Leuven
Department Name
Respiratory diseases
Principal Investigator Name
Christophe Dooms
Principal Investigator Email
christophe.dooms@uzleuven.be
Contact Person Name
Christophe Dooms
Contact Person Email
christophe.dooms@uzleuven.be

Netherlands

Earliest CTIS Part Ii Submission Date
26-06-2024
Latest Decision Or Authorization Date
16-02-2026
Processing Time Days
600
Number Of Sites
3
Number Of Participants
15

Sites

Site Name
Radboud universitair medisch centrum / RADBOUDUMC
Department Name
Pulmonary Diseases
Principal Investigator Name
Chantal Smits
Principal Investigator Email
chantal.smits-vandergraaf@radboudumc.nl
Contact Person Name
Chantal Smits
Site Name
Universitair Medisch Centrum Groningen
Department Name
Pulmonary Oncology
Principal Investigator Name
Anthonie van der Wekken
Principal Investigator Email
a.j.van.der.wekken@umcg.nl
Contact Person Name
Anthonie van der Wekken
Contact Person Email
a.j.van.der.wekken@umcg.nl
Site Name
VUmc Stichting
Department Name
Pulmonary Disease
Principal Investigator Name
Sayed Hashemi
Principal Investigator Email
s.hashemi@amsterdamumc.nl
Contact Person Name
Sayed Hashemi
Contact Person Email
s.hashemi@amsterdamumc.nl

Italy

Earliest CTIS Part Ii Submission Date
26-06-2024
Latest Decision Or Authorization Date
17-02-2026
Processing Time Days
601
Number Of Sites
6
Number Of Participants
50

Sites

Site Name
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Principal Investigator Name
Silvia Novello
Principal Investigator Email
silvia.novello@unito.it
Contact Person Name
Silvia Novello
Contact Person Email
silvia.novello@unito.it
Site Name
Azienda Ospedaliero Universitaria Parma
Principal Investigator Name
Marcello Tiseo
Principal Investigator Email
mtiseo@ao.pr.it
Contact Person Name
Marcello Tiseo
Contact Person Email
mtiseo@ao.pr.it
Site Name
Centro Ricerche Cliniche Di Verona S.r.l.
Principal Investigator Name
Sara Pilotto
Principal Investigator Email
sara.pilotto@univr.it
Contact Person Name
Sara Pilotto
Contact Person Email
sara.pilotto@univr.it
Site Name
Istituto Europeo Di Oncologia S.r.l.
Principal Investigator Name
Filippo De Marinis
Principal Investigator Email
filippo.demarinis@ieo.it
Contact Person Name
Filippo De Marinis
Contact Person Email
filippo.demarinis@ieo.it
Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Principal Investigator Name
Diego Luigi Cortinovis
Principal Investigator Email
d.cortinovis@hsgerardo.org
Contact Person Name
Diego Luigi Cortinovis
Contact Person Email
d.cortinovis@hsgerardo.org
Site Name
Universita Cattolica Del Sacro Cuore
Principal Investigator Name
Emilio Bria
Principal Investigator Email
emilio.bria@policlinicogemelli.it
Contact Person Name
Emilio Bria

Sponsor

Primary sponsor

Full Name
AstraZeneca AB
Organisation Type
Pharmaceutical company
Country Of Registered Address
Sweden

Third parties

  • {"country":"Denmark","full_name":"Astrazeneca A/S","duties_or_roles":"Sponsor duties code: 1","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
DS-8201a
Active Substance
TRASTUZUMAB DERUXTECAN
Modality
ADC
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
prodAuthStatus: 1
Investigational Product Name
PEMBROLIZUMAB
Active Substance
PEMBROLIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
prodAuthStatus: 2
Investigational Product Name
CISPLATIN
Active Substance
CISPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
prodAuthStatus: 2
Investigational Product Name
CARBOPLATIN
Active Substance
CARBOPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
prodAuthStatus: 2
Investigational Product Name
PEMETREXED
Active Substance
PEMETREXED
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
prodAuthStatus: 2
Combination Treatment
Yes

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