Clinical trial • Phase III • Oncology

OSIMERTINIB for Non-small cell lung cancer (EGFR mutation-positive, non-squamous, locally advanced or metastatic)

Phase III trial of OSIMERTINIB for Non-small cell lung cancer (EGFR mutation-positive, non-squamous, locally advanced or metastatic).

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Non-small cell lung cancer (EGFR mutation-positive, non-squamous, locally advanced or metastatic)
Trial Stage
Phase III
Drug Modality
Small molecule|ADC

Key dates

Initial CTIS Submission Date
19-08-2024
First CTIS Authorization Date
26-11-2024

Trial design

Randomised, open-label, osimertinib (tagrisso 40 mg or 80 mg oral tablets) alone versus osimertinib plus datopotamab deruxtecan (datopotamab deruxtecan, intravenous, sponsor code ds-1062a; dose in mg/kg per protocol not stated in part i data).-controlled Phase III trial in Germany, France, Italy and others.

Randomised
Yes
Open Label
Yes
Comparator
Osimertinib (TAGRISSO 40 mg or 80 mg oral tablets) alone versus Osimertinib plus Datopotamab deruxtecan (Datopotamab deruxtecan, intravenous, sponsor code DS-1062a; dose in mg/kg per protocol not stated in Part I data).
Target Sample Size
501

Eligibility

Recruits 501 No vulnerable population selected (isVulnerablePopulationSelected: false). Study enrols adults (≥ 18 years). Subject information sheets and informed consent forms are provided for adult participants and specific ICFs are available for pregnant partners and optional genomics/multiomics; no assent procedures for minors are described..

Vulnerable Population
No vulnerable population selected (isVulnerablePopulationSelected: false). Study enrols adults (≥ 18 years). Subject information sheets and informed consent forms are provided for adult participants and specific ICFs are available for pregnant partners and optional genomics/multiomics; no assent procedures for minors are described.

Inclusion criteria

  • {"criterion_text":"- 1. Participant must be ≥ 18 years"}
  • {"criterion_text":"- 2. Histologically or cytologically documented nonsquamous NSCLC.NSCLC of mixed histology is allowed if adenocarcinoma is the predominant histology. Mixed small-cell lung cancer and NSCLC histology, and sarcomatoid variant of NSCLC is ineligible."}
  • {"criterion_text":"- 3. Stage IIIB or IIIC or Stage IV metastatic NSCLC or recurrent NSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative surgery or definitive chemoradiation at the time of randomisation."}
  • {"criterion_text":"- 4. Participants must not have received prior EGFR TKIs or other systemic therapy for Stage IIIB, IIIC or IV NSCLC."}
  • {"criterion_text":"- 5. The tumour harbors 1 of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with other genomic alterations, which may include EGFR T790M, assessed by a CLIA-certified (US sites) or an accredited (outside of the US) local laboratory or by central prospective tissue testing."}
  • {"criterion_text":"- 6. For participants enrolled in randomisation period, mandatory provision of an unstained, archival tumour tissue sample in a quantity sufficient to allow for central confirmation of the EGFR mutation status."}
  • {"criterion_text":"- 8. 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 ≥15 mm) with CT or MRI and is suitable for accurate repeated measurements."}

Exclusion criteria

  • {"criterion_text":"- 2. Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of osimertinib."}
  • {"criterion_text":"- 12. Pulmonary embolism within 3 months of the study enrolment or has severe pulmonary function compromise."}
  • {"criterion_text":"- 13. Prior exposure to any agent including an ADC containing a chemotherapeutic agent targeting topoisomerase I, TROP2-targeted therapy."}
  • {"criterion_text":"- 4. Spinal cord compression and unstable brain metastases, as defined by Protocol."}
  • {"criterion_text":"- 5. Clinically significant corneal disease."}
  • {"criterion_text":"- 6. Has active or uncontrolled hepatitis B or C virus infection, as defined by Protocol."}
  • {"criterion_text":"- 7. Known HIV infection that is not well controlled, as defined by Protocol."}
  • {"criterion_text":"- 8. Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections (participants with localised fungal infections of skin or nails are eligible)."}
  • {"criterion_text":"- 9. Resting ECG with clinically abnormal findings, as defined by Protocol."}
  • {"criterion_text":"- 10. Uncontrolled or significant cardiac disease, as defined by Protocol."}
  • {"criterion_text":"- 11. Past medical history of ILD/penumonitis, including radiation pneumonitis (apart from radiation pneumonitis that did not require steroids), or drug-induced ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause (in the absence of progression).","definition_or_measurement_approach":"PFS defined as time from randomisation until progression per RECIST 1.1 assessed by Blinded Independent Central Review (BICR), or death due to any cause (if no progression)."}

Secondary endpoints

  • {"endpoint_text":"- 1. OS defined as the time from randomisation until the date of death due to any cause.","definition_or_measurement_approach":"Overall survival (OS): time from randomisation until date of death due to any cause."}
  • {"endpoint_text":"- 2. Central nervous system progression-free survival (CNS PFS) is defined as the time from randomisation until the date of objective CNS progression assessed by CNS BICR or death (by any cause in absence of CNS progression).","definition_or_measurement_approach":"CNS PFS: time from randomisation to objective CNS progression assessed by CNS BICR or death (any cause) if no CNS progression."}
  • {"endpoint_text":"- 3. PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by investigator, or death due to any cause (in the absence of progression).","definition_or_measurement_approach":"Investigator-assessed PFS per RECIST 1.1: time from randomisation until progression (INV) or death."}
  • {"endpoint_text":"- 4. ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, as determined by BICR (and investigator) per RECIST 1.1.","definition_or_measurement_approach":"ORR: proportion with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 by BICR (and investigator)."}
  • {"endpoint_text":"- 5. DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by BICR (and investigator) assessment or death due to any cause. The measure of interest is the median of DoR.","definition_or_measurement_approach":"Duration of Response (DoR): time from first documented confirmed response to documented progression per RECIST 1.1 (BICR and investigator) or death; median DoR is primary measure."}
  • {"endpoint_text":"- 6. Neuro-radiologist assessments according to CNS RECIST 1.1 to determine the presence/absence of CNS lesions at progression in participants without CNS metastases at baseline.","definition_or_measurement_approach":"Neuroradiologist assessments per CNS RECIST 1.1 to determine CNS lesion status at progression in participants without baseline CNS metastases."}
  • {"endpoint_text":"- 7. PFS2 will be defined as the time from randomisation to the earliest of the progression event (following the initial progression) subsequent to first subsequent anti-cancer therapy, or death.","definition_or_measurement_approach":"PFS2: time from randomisation to earliest progression event after initial progression following first subsequent anti-cancer therapy, or death."}

Recruitment

Planned Sample Size
501
Recruitment Window Months
88
Consent Approach
Informed consent is obtained using subject information sheets and informed consent forms (L1_SIS and ICF) for adult participants. Separate ICFs are available for pregnant partners and optional genomic/multiomics consent. Translated ICF/SIS documents are available (examples in Germany, Poland, France, Spain, Italy). Participants provide their own consent (adults ≥18); no assent procedures for minors are described.

Geography

Total Number Of Sites
30
Total Number Of Participants
74

Germany

Earliest CTIS Part Ii Submission Date
14-11-2024
Latest Decision Or Authorization Date
18-12-2025
Processing Time Days
399
Number Of Sites
9
Number Of Participants
18

Sites

Site Name
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Department Name
Klinik für Pneumologie (Clinic for Pneumology)
Contact Person Name
Juergen Alt
Site Name
Universitaetsklinikum Schleswig-Holstein AöR
Department Name
Klinik für Innere Medizin II - Haematologie und Onkologie
Contact Person Name
Matthias Ritgen
Contact Person Email
m.ritgen@med2.uni-kiel.de
Site Name
Evangelische Lungenklinik Berlin Krankenhausbetriebs gGmbH
Department Name
Klinik für Pneumologie
Contact Person Name
Christian Grohe
Contact Person Email
Christian.Grohe@pgdiakonie.de
Site Name
Universitaetsmedizin Goettingen
Department Name
Klinik für Hämatologie und Medizinische Onkologie
Contact Person Name
Tobias Overbeck
Site Name
Lungenfachklinik Immenhausen
Contact Person Name
Achim Rittmeyer
Site Name
HELIOS Klinikum Erfurt GmbH
Department Name
Klinik für Pneumologie, Schlaf- und Beatmungsmedizin
Contact Person Name
Wolf Brunner
Site Name
Krankenhaus Nordwest GmbH
Department Name
Institut für Klinisch-Onkologische Forschung
Contact Person Name
Akin Atmaca
Contact Person Email
atmaca.akin@khnw.de
Site Name
Muenchen Klinik gGmbH
Department Name
Klinik für Pneumologie und Pneumologische Onkologie
Contact Person Name
Konrad Kokowski
Site Name
Kliniken der Stadt Koeln gGmbH
Department Name
Lungenklinik Köln-Merheim
Contact Person Name
Carolin Gross-Ophoff-Mueller

France

Earliest CTIS Part Ii Submission Date
27-02-2025
Latest Decision Or Authorization Date
01-12-2025
Processing Time Days
277
Number Of Sites
4
Number Of Participants
8

Sites

Site Name
Centre Hospitalier Regional De Marseille
Department Name
Service d'Oncologie Multidisciplinaire et Innovations Thérapeutiques
Contact Person Name
Pascale TOMASINI
Contact Person Email
pascale.tomasini@ap-hm.fr
Site Name
Institut Curie
Department Name
Oncologie Medicale
Contact Person Name
Nicolas GIRARD
Contact Person Email
nicolas.girard2@curie.fr
Site Name
Institut De Cancerologie De L Ouest
Department Name
Departement d'Oncologie médicale
Contact Person Name
Judith RAIMBOURG
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Oncologie Thoracique
Contact Person Name
Celine MASCAUX

Italy

Earliest CTIS Part Ii Submission Date
02-09-2024
Latest Decision Or Authorization Date
23-12-2025
Processing Time Days
477
Number Of Sites
5
Number Of Participants
15

Sites

Site Name
Istituto Oncologico Veneto
Department Name
UOC Chirurgia, Oncologia e Gastroenterologia
Contact Person Name
Laura Bonanno
Contact Person Email
laura.bonanno@iov.veneto.it
Site Name
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Department Name
Dipartimento di Oncologia Polmonare
Contact Person Name
Silvia Novello
Contact Person Email
silvia.novello@unito.it
Site Name
Istituto Europeo Di Oncologia S.r.l.
Department Name
Divisione Clinica di Oncologia Toracica
Contact Person Name
Antonio Passaro
Contact Person Email
antonio.passaro@ieo.it
Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Department Name
U.O.C. Oncologia Medica
Contact Person Name
Diego Luigi Cortinovis
Site Name
Azienda Ospedaliero Universitaria Parma
Department Name
Dipartimento di Oncologia Medica
Contact Person Name
Marcello Tiseo
Contact Person Email
mtiseo@ao.pr.it

Poland

Earliest CTIS Part Ii Submission Date
31-10-2024
Latest Decision Or Authorization Date
16-12-2025
Processing Time Days
411
Number Of Sites
5
Number Of Participants
15

Sites

Site Name
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy
Department Name
Ambulatorium Chemioterapii
Contact Person Name
Bogdan Zurawski
Contact Person Email
zurawskib@co.bydgoszcz.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
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
Centrum Pulmonologii I Torakochirurgii W Bystrej
Department Name
Oddzial Pulmonologiczno – Onkologiczny z Chemioterapią
Contact Person Name
Adrianna Gega-Czarnota
Contact Person Email
adrianna.gega@gmail.com
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Klinika Nowotworow Pluc i Klatki Piersiowej
Contact Person Name
Adam Pluzanski
Contact Person Email
adam.pluzanski@nio.gov.pl

Spain

Earliest CTIS Part Ii Submission Date
10-10-2024
Latest Decision Or Authorization Date
07-04-2026
Processing Time Days
544
Number Of Sites
7
Number Of Participants
18

Sites

Site Name
Complexo Hospitalario Universitario A Coruna
Department Name
Oncology
Contact Person Name
Maria Rosario Garcia Campelo
Site Name
Hospital Universitario Puerta De Hierro De Majadahonda
Department Name
Oncology
Contact Person Name
Mariano Provencio Pulla
Contact Person Email
mprovenciop@gmail.com
Site Name
Hospital Clinic De Barcelona
Department Name
Oncology
Contact Person Name
Noemi Reguart Aransay
Contact Person Email
nreguart@clinic.cat
Site Name
Fundacion Instituto Valenciano De Oncologia
Department Name
Oncology
Contact Person Name
Sergio Sandiego Contreras
Contact Person Email
ssandiego@fivo.org
Site Name
Hospital Universitario Clinico San Cecilio
Department Name
Oncology
Contact Person Name
Silvia Sequero Lopez
Contact Person Email
silsq90@gmail.com
Site Name
Hospital Universitario Fundacion Jimenez Diaz
Department Name
Oncology
Contact Person Name
Manuel Domine Gomez
Contact Person Email
mdomine@fjd.es
Site Name
Hospital Universitario Puerta De Hierro De Majadahonda (additional listed site entry)
Department Name
Oncology

Sponsor

Primary sponsor

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

Investigational products

Investigational Product Name
TAGRISSO 40 mg film-coated tablets
Active Substance
OSIMERTINIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Marketing authorisation (approved product: EU marketing authorisation present)
Investigational Product Name
TAGRISSO 80 mg film-coated tablets
Active Substance
OSIMERTINIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Marketing authorisation (approved product: EU marketing authorisation present)
Investigational Product Name
Datopotamab deruxtecan
Active Substance
DATOPOTAMAB DERUXTECAN
Modality
ADC
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Authorisation Status
Investigational product (no marketing authorisation information in Part I)
Combination Treatment
Yes

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