Clinical trial • Phase III • Oncology

DATOPOTAMAB DERUXTECAN for Non-small cell lung cancer (non-squamous, advanced/metastatic) | TROP2-positive non-small cell lung cancer without actionable genomic alterations

Phase III trial of DATOPOTAMAB DERUXTECAN for Non-small cell lung cancer (non-squamous, advanced/metastatic) | TROP2-positive non-small cell lung cancer w…

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Non-small cell lung cancer (non-squamous, advanced/metastatic) | TROP2-positive non-small cell lung cancer without actionable genomic alterations
Trial Stage
Phase III
Drug Modality
ADC | Small molecule

Key dates

Initial CTIS Submission Date
24-10-2025
First CTIS Authorization Date
26-02-2026

Trial design

Randomised, open-label, docetaxel (comparator; dose and schedule not specified)-controlled Phase III trial in Austria, Belgium, Hungary and others.

Randomised
Yes
Open Label
Yes
Comparator
DOCETAXEL (Comparator; dose and schedule not specified)
Biomarker Stratified
True, biomarker: TROP2 QCS-NMR positive
Target Sample Size
297

Eligibility

Recruits 297 adults.

Inclusion criteria

  • {"criterion_text":"- Pathologically documented Stage IIIB, IIIC, or Stage IV non-squamous NSCLC without AGA at the time of randomisation and meets the criteria for NSCLC: * Participants must have documented negative test results for EGFR, ALK, and ROS1 genomic alterations. * Has no known tumour genomic alterations in NTRK, BRAF, RET, MET exon 14 skipping, KRAS G12C, HER2 or any other actionable driver oncogenes for which there are locally approved and available targeted first-line therapies. * Prospectively assessed TROP2 QCS-NMR positive based on results from an appropriately validated investigational TROP2 RxDx device."}
  • {"criterion_text":"- Documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC."}
  • {"criterion_text":"- Participants must have received platinum-based chemotherapy (PBC) in combination with anti-PD-1/anti-PD-L1 mAb as the only prior line of therapy or received PBC and anti-PD-1/anti-PD-L1 monoclonal antibody (in either order) sequentially as the only 2 prior lines of therapy."}
  • {"criterion_text":"- Provision of acceptable FFPE tumour sample for assessment of TROP2."}
  • {"criterion_text":"- At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15mm) with CT or MRI and is suitable for accurate repeated measurements."}
  • {"criterion_text":"- ECOG PS of 0 or 1."}
  • {"criterion_text":"- Adequate bone marrow reserve and organ function within 7 days before randomisation."}

Exclusion criteria

  • {"criterion_text":"- Squamous, mixed NSCLC, or SCLC histology."}
  • {"criterion_text":"- Has severe pulmonary function compromise per Investigator discretion."}
  • {"criterion_text":"- NSCLC disease that is eligible for definitive local therapy alone."}
  • {"criterion_text":"- History of another primary malignancy other than NSCLC, except for malignancy treated with curative intent with no known active disease within 3 years before randomisation and of low potential risk for recurrence."}
  • {"criterion_text":"- Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring treatment with corticosteroids or anticonvulsants for at least 7 days prior to randomisation."}
  • {"criterion_text":"- Clinically significant corneal disease."}
  • {"criterion_text":"- Has active or uncontrolled hepatitis B or C virus infection."}
  • {"criterion_text":"- Known HIV infection that is not well controlled."}
  • {"criterion_text":"- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals."}
  • {"criterion_text":"- History of non-infectious ILD/pneumonitis including radiation pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- To assess the superiority of Dato-DXd vs docetaxel by assessment of PFS by BICR according to RECIST v1.1 in participants with TROP2 QCS-NMR positive non-squamous NSCLC without AGA.","definition_or_measurement_approach":"Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) according to RECIST v1.1."}
  • {"endpoint_text":"- To assess the superiority of Dato-DXd vs docetaxel by assessment of OS in participants with TROP2 QCS-NMR positive non-squamous NSCLC without AGA.","definition_or_measurement_approach":"Overall survival (OS) (assessment of survival outcome)."}

Secondary endpoints

  • {"endpoint_text":"- Objective response rate (ORR)","definition_or_measurement_approach":"Objective response rate as listed (ORR)."}
  • {"endpoint_text":"- Duration of response (DoR)","definition_or_measurement_approach":"Duration of response (DoR) as listed."}
  • {"endpoint_text":"- Time to second progression or death (PFS2)","definition_or_measurement_approach":"Time to second progression or death (PFS2) as listed."}
  • {"endpoint_text":"- Characterise population PK and its relationship with efficacy and safety endpoints, and evaluate the effects of covariates on PK, efficacy, and safety","definition_or_measurement_approach":"Population pharmacokinetics (PK) characterization and exposure-response analyses relating PK to efficacy and safety; evaluation of covariate effects."}
  • {"endpoint_text":"- Presence of antidrug antibody (ADAs) for Dato-DXd","definition_or_measurement_approach":"Assessment of antidrug antibody (ADA) presence for Dato-DXd."}
  • {"endpoint_text":"- Time to deterioration (TTD) in pulmonary symptoms, physical functioning, and in GHS/QoL","definition_or_measurement_approach":"Time to deterioration (TTD) measured for pulmonary symptoms, physical functioning, and global health status/quality of life (GHS/QoL)."}
  • {"endpoint_text":"- To assess TROP2 diagnostic test performance and relationship with other tumour-derived biomarkers or diagnostics tests, and support test development","definition_or_measurement_approach":"Assessment of diagnostic test performance for TROP2 and its relationship with other tumour-derived biomarkers/tests; support for diagnostic development."}
  • {"endpoint_text":"- To assess the safety and tolerability of Dato-DXd vs docetaxel in participants with TROP2 QCS-NMR positive non-squamous NSCLC without AGA","definition_or_measurement_approach":"Safety and tolerability assessment (adverse events, tolerability measures) comparing Dato-DXd and docetaxel."}

Recruitment

Planned Sample Size
297
Recruitment Window Months
39
Consent Approach
Informed consent obtained from adult participants. Subject information and informed consent form (L1_SIS and ICF) documents are provided (including Main Adults, Pre-screening, Pregnant Partner) and ICFs/recruitment materials are available in multiple country languages (examples in document titles: English, Dutch, French, German, Hungarian, Polish, Spanish, Italian).

Geography

Total Number Of Sites
58
Total Number Of Participants
103

Austria

Earliest CTIS Part Ii Submission Date
25-02-2026
Latest Decision Or Authorization Date
09-03-2026
Processing Time Days
12
Number Of Sites
5
Number Of Participants
11

Sites

Site Name
Vorarlberger Krankenhaus-Betriebsgesellschaft mbH
Department Name
Internal E at LKH Rankweil
Contact Person Name
Thomas Winder
Contact Person Email
thomas.winder@lkhf.at
Site Name
Medical University Of Graz
Department Name
Clinical Department of Oncology
Contact Person Name
Gudrun Absenger
Contact Person Email
gudrun.absenger@medunigraz.at
Site Name
Kepler Universitaetsklinikum GmbH
Department Name
University Hospital for Internal Medicine - Pneumology
Contact Person Name
David Lang
Site Name
Stadt Wien Wiener Gesundheitsverbund
Department Name
Department for Internal Medicine and Pneumology
Contact Person Name
Maximilian Hochmair
Site Name
Stadt Wien Wiener Gesundheitsverbund
Department Name
Site Penzing of Clinic Ottakring
Contact Person Name
Marie Kathrin Breyer

Belgium

Earliest CTIS Part Ii Submission Date
04-02-2026
Latest Decision Or Authorization Date
02-03-2026
Processing Time Days
26
Number Of Sites
6
Number Of Participants
10

Sites

Site Name
Centre Hospitalier Universitaire Dinant Godinne Sainte-Elisabeth-UCL-Namur
Department Name
Department of Oncology
Contact Person Name
Sebahat Ocak
Contact Person Email
sebahat.ocak@uclouvain.be
Site Name
Jessa Ziekenhuis
Department Name
Department of Oncology
Contact Person Name
Kristof Cuppens
Contact Person Email
kristof.cuppens@jessazh.be
Site Name
Hopital De Libramont
Department Name
Department of Oncology
Contact Person Name
Frédéric Forget
Contact Person Email
frederic.forget@vivalia.be
Site Name
Vitaz
Department Name
Department of Oncology
Contact Person Name
Koen Deschepper
Contact Person Email
koen.deschepper@vitaz.be
Site Name
CHU Helora
Department Name
Department of Oncology
Contact Person Name
Gaetan Catala
Contact Person Email
gaetan.catala@jolimont.be
Site Name
CHU Helora
Department Name
Department of Oncology
Contact Person Name
Gaetan Catala
Contact Person Email
gaetan.catala@jolimont.be

Hungary

Earliest CTIS Part Ii Submission Date
12-01-2026
Latest Decision Or Authorization Date
26-02-2026
Processing Time Days
45
Number Of Sites
9
Number Of Participants
13

Sites

Site Name
Reformatus Pulmonologiai Centrum
Department Name
Onkológiai kúra,- fekvőbeteg ellátás
Contact Person Name
Gabriella Gálffy
Contact Person Email
galffy.gabriella@rpckorhaz.hu
Site Name
Budapesti Uzsoki Utcai Korhaz
Department Name
Tüdőgyógyászati osztály
Contact Person Name
Csaba Máthé
Contact Person Email
mathe.csaba@uzsoki.hu
Site Name
University Of Debrecen
Department Name
Tüdőgyógyászati Klinika
Contact Person Name
Tamás Kardos
Contact Person Email
kardostom@yahoo.co.uk
Site Name
Matrai Gyogyintezet
Department Name
Bronchológiai Osztály
Contact Person Name
István Albert
Contact Person Email
albert.magy@gmail.com
Site Name
Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktato Korhaz
Department Name
Pulmonológiai Osztály
Contact Person Name
Zsuzsanna Szalai
Contact Person Email
clinstudy@gmail.com
Site Name
Clinic Of Pulmonology Semmelweis University
Department Name
Pulmonológiai Klinika
Contact Person Name
Veronika Müller
Contact Person Email
muller.veronika@semmelweis.hu
Site Name
Bacs-Kiskun Varmegyei Oktatokorhaz
Department Name
Onkoradiológiai Központ
Contact Person Name
Zsuzsanna Kelemen
Site Name
Bekes Varmegyei Koezponti Korhaz
Department Name
Aktív Tüdőgyógyászati Osztály
Contact Person Name
Ibolya Laczó
Contact Person Email
laczoibolya@gmail.com
Site Name
Orszagos Koranyi Pulmonologiai Intezet
Department Name
XIV. Pulmonológiai Osztály
Contact Person Name
Judit Moldvay
Contact Person Email
sotersz@freemail.hu

Italy

Earliest CTIS Part Ii Submission Date
28-01-2026
Latest Decision Or Authorization Date
03-03-2026
Processing Time Days
34
Number Of Sites
6
Number Of Participants
12

Sites

Site Name
ASST Grande Ospedale Metropolitano Niguarda
Department Name
SC Oncologia Falck
Contact Person Name
Giulio Cerea
Site Name
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Department Name
SCDU Medical Oncology
Contact Person Name
Silvia Novello
Contact Person Email
silvia.novello@unito.it
Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Department Name
U.O.C. Oncologia Medica
Contact Person Name
Diego Cortinovis
Site Name
Istituto Oncologico Veneto
Department Name
Department of Surgery, Oncology and Gastroenterology
Contact Person Name
Laura Bonanno
Contact Person Email
laura.bonanno@iov.veneto.it
Site Name
Istituto Europeo Di Oncologia S.r.l.
Department Name
Thoracic Oncology Division
Contact Person Name
Antonio Passaro
Contact Person Email
antonio.passaro@ieo.it
Site Name
Humanitas Mirasole S.p.A.
Department Name
Operative Unit of Oncology and Hematology
Contact Person Name
Armando Santoro

Spain

Earliest CTIS Part Ii Submission Date
05-02-2026
Latest Decision Or Authorization Date
02-03-2026
Processing Time Days
25
Number Of Sites
8
Number Of Participants
13

Sites

Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncology
Contact Person Name
Jon Zugazagoitia Fraile
Contact Person Email
j.zugazagoitia.imas12@h12o.es
Site Name
Complexo Hospitalario Universitario A Coruna
Department Name
Oncology
Contact Person Name
Mª Rosario Garcia Campelo
Site Name
Hospital Clinico Universitario Lozano Blesa
Department Name
Oncology
Contact Person Name
Dolores Isla Casado
Contact Person Email
lola.isla@gmail.com
Site Name
Institut Catala D'oncologia
Department Name
Oncology
Contact Person Name
Noelia Vilariño Quintela
Contact Person Email
nvilarino@iconcologia.net
Site Name
Hospital Universitario Virgen De La Macarena
Department Name
Oncology
Contact Person Name
David Vicente Baz
Contact Person Email
david.vbaz@gmail.com
Site Name
Hospital Universitario Regional De Malaga
Department Name
Oncology
Contact Person Name
Alexandra Cantero Gonzalez
Site Name
Hospital Universitari Vall D Hebron
Department Name
Oncology
Contact Person Name
Enriqueta Felip Font
Contact Person Email
efelip@vhio.net
Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncology
Contact Person Name
Jon Zugazagoitia Fraile
Contact Person Email
j.zugazagoitia.imas12@h12o.es

Poland

Earliest CTIS Part Ii Submission Date
25-02-2026
Latest Decision Or Authorization Date
07-03-2026
Processing Time Days
10
Number Of Sites
4
Number Of Participants
10

Sites

Site Name
Warminsko-Mazurskie Centrum Chorob Pluc W Olsztynie
Department Name
Oddzial Onkologii z Pododdzialem chemioterapii
Contact Person Name
Jaroslaw Kolb-Sielecki
Contact Person Email
j.kolbsielecki@gmail.com
Site Name
Instytut Centrum Zdrowia Matki Polki
Department Name
Klinika Onkologii
Contact Person Name
Ewa Kalinka
Contact Person Email
ewakalinka@wp.pl
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Klinika Nowotworow Pluca i Klatki Piersiowej
Contact Person Name
Adam Pluzanski
Contact Person Email
adam.pluzanski@nio.gov.pl
Site Name
Wielkopolskie Centrum Pulmonologii I Torakochirurgii Im. Eugenii I Janusza Zeylandow
Department Name
Oddzial Onkologii Klinicznej z Pododdzialem dziennej chemioterapii
Contact Person Name
Katarzyna Stencel
Contact Person Email
kstencel@wcpit.org

France

Earliest CTIS Part Ii Submission Date
15-01-2026
Latest Decision Or Authorization Date
03-03-2026
Processing Time Days
47
Number Of Sites
5
Number Of Participants
12

Sites

Site Name
Centre Hospitalier Regional De Marseille
Department Name
Medical oncology
Contact Person Name
Pascale Tomasini
Contact Person Email
pascale.tomasini@ap-hm.fr
Site Name
Hopital Ambroise Pare
Department Name
Respiratory diseases and thoraci oncology
Contact Person Name
Etienne Giroux-Leprieur
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Medical oncology
Contact Person Name
Elvire PONS TOSTIVINT
Contact Person Email
elvire.pons@chu-nantes.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Pneumology
Contact Person Name
Julien Mazières
Contact Person Email
mazieres.j@chu-toulouse.fr
Site Name
Centre Leon Berard
Department Name
Medical oncology
Contact Person Name
Aurélie Swalduz

Germany

Earliest CTIS Part Ii Submission Date
03-02-2026
Latest Decision Or Authorization Date
03-03-2026
Processing Time Days
28
Number Of Sites
15
Number Of Participants
22

Sites

Site Name
Klinikum Der Landeshauptstadt Stuttgart gKAöR
Department Name
Klinik für Pneumologie und Beatmungsmedizin
Contact Person Name
Cornelia Kropf-Sanchen
Contact Person Email
c.kropf@klinikum-stuttgart.de
Site Name
Onkologie Rheinsieg Praxisnetzwerk
Department Name
Ueberoertl. GP Forstbauer / Rheis / Rodermann / Ziske
Contact Person Name
Andreas Diel
Contact Person Email
diel@onkologie-rheinsieg.de
Site Name
Asklepios Klinik Gauting GmbH
Department Name
Thorakale Onkologie
Contact Person Name
Niels Reinmuth
Contact Person Email
n.reinmuth@asklepios.com
Site Name
Kliniken der Stadt Koeln gGmbH
Department Name
Studienzentrum der Lungenklinik Krankenhaus Merheim
Contact Person Name
Carolin Gross-Ophoff-Mueller
Site Name
Universitaetsklinikum Bonn AöR
Department Name
Medizinische Klinik III
Contact Person Name
Tessa Hattenhauer
Contact Person Email
Tessa.Hattenhauer@ukbonn.de
Site Name
Evangelisches Klinikum Bethel gGmbH
Department Name
Klinik fuer Innere Medizin, Haematologie, Onkologie
Contact Person Name
Kristin Sauerland
Contact Person Email
kristin.sauerland@evkb.de
Site Name
Universitaetsklinikum Essen AöR
Department Name
Innere Klinik Westdeutsches Tumorzentrum
Contact Person Name
Halime Kalkavan
Contact Person Email
Halime.kalkavan@uk-essen.de
Site Name
Krankenhaus Nordwest GmbH
Department Name
Institut fuer Klinisch-Onkologische Forschung
Contact Person Name
Akin Atmaca
Contact Person Email
atmaca.akin@khnw.de
Site Name
Haemato-Onkologie Hamburg - Prof. Laack und Partner
Department Name
Studiengesellschaft
Contact Person Name
Eckart Laack
Site Name
HELIOS Klinikum Krefeld GmbH
Department Name
Pneumologie
Contact Person Name
Benoit Kraemer
Site Name
MVZ-Onkologie Velbert GbR
Contact Person Name
Arnd Nusch
Contact Person Email
nusch@aol.com
Site Name
Thoraxklinik Heidelberg gGmbH
Department Name
Thoraxklinik Heidelberg
Contact Person Name
Michael Thomas
Site Name
Muehlenkreiskliniken AöR
Department Name
Universitaetsklinik fuer Haematologie, Onkologie, Gerinnungsstoerungen und Palliativmedizin
Contact Person Name
Parvis Sadjadian
Site Name
Pius-Hospital Oldenburg
Department Name
Klinik für Haematologie und Onkologie
Contact Person Name
Frank Griesinger
Site Name
HELIOS Klinikum Bad Saarow GmbH
Department Name
Clinic for Oncology and Palliative Care
Contact Person Name
Daniel Pink

Sponsor

Primary sponsor

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

Investigational products

Investigational Product Name
Datopotamab deruxtecan
Active Substance
DATOPOTAMAB DERUXTECAN
Modality
ADC
Routes Of Administration
INTRAVENOUS USE
Route
INTRAVENOUS USE
Investigational Product Name
DOCETAXEL
Active Substance
DOCETAXEL
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
INTRAVENOUS USE

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