Clinical trial • Phase III • Oncology

N-[2-[2-(DIMETHYLAMINO)ETHYL-METHYLAMINO]-5-[[4-(1-METHYLINDOL-3-YL)PYRIMIDIN-2-YL]AMINO]-6-(2,2,2-TRIFLUOROETHOXY)PYRIDIN-3-YL]PROP-2-ENAMIDE for Non-small cell lung cancer | Advanced or metastatic non-small cell lung cancer with EGFR PACC uncommon mutations

Phase III trial of N-[2-[2-(DIMETHYLAMINO)ETHYL-METHYLAMINO]-5-[[4-(1-METHYLINDOL-3-YL)PYRIMIDIN-2-YL]AMINO]-6-(2,2,2-TRIFLUOROETHOXY)PYRIDIN-3-YL]PROP-2-…

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Non-small cell lung cancer | Advanced or metastatic non-small cell lung cancer with EGFR PACC uncommon mutations
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
15-08-2025
First CTIS Authorization Date
10-12-2025

Trial design

Randomised, open-label, investigator's choice comparator arms: osimertinib 80 mg qd; afatinib 40 mg qd-controlled Phase III trial across 22 sites in Italy, Greece, France and others.

Randomised
Yes
Open Label
Yes
Comparator
Investigator's choice comparator arms: Osimertinib 80 mg QD; Afatinib 40 mg QD
Target Sample Size
352

Eligibility

Recruits 352 Vulnerable population flag selected. Country-specific subject information and informed consent forms are provided (examples: L1_*_SIS-ICF_Main, L1_*_SIS-ICF_Pregnant Participant, L1_*_SIS-ICF_Pregnant Partner) in multiple languages (Italian, Greek, French, Spanish). Consent is obtained from participants via these SIS-ICF forms; no specific assent or parental consent procedures for minors are described in the provided materials..

Vulnerable Population
Vulnerable population flag selected. Country-specific subject information and informed consent forms are provided (examples: L1_*_SIS-ICF_Main, L1_*_SIS-ICF_Pregnant Participant, L1_*_SIS-ICF_Pregnant Partner) in multiple languages (Italian, Greek, French, Spanish). Consent is obtained from participants via these SIS-ICF forms; no specific assent or parental consent procedures for minors are described in the provided materials.

Inclusion criteria

  • {"criterion_text":"- 1. Histologically or cytologically documented, locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy.\n- 2. Documented results of the presence of an Epidermal Growth Factor Receptor (EGFR) PACC mutation in tumor tissue or blood from local testing.\n- 3. No prior systemic anticancer therapy regimens received for locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) including prior treatment with any Epidermal Growth Factor Receptor (EGFR)-targeting agents (e.g., previous (EGFR) TKIs, monoclonal antibodies, or bispecific antibodies).\n- 4. Patients who have received prior neo-adjuvant and/or adjuvant chemotherapy, immunotherapy, or chemo radiotherapy for non-metastatic disease must have experienced a treatment free interval of at least 12 months.\n- 5. Patients with asymptomatic CNS metastases are eligible"}

Exclusion criteria

  • {"criterion_text":"- 1. Have NSCLC with any of the following EGFR mutations: exon 19 deletion, L858R, or C797S\n- 2. Have had prior treatment with EGFR-targeted agents (eg, EGFR-TKIs, EGFR-targeted proteolysis-targeting chimeras [PROTACs], monoclonal antibodies, or bispecific antibodies)\n- 3. Have had prior treatment with any systemic anti-cancer therapy for locally advanced or metastatic NSCLC not amenable to curative surgery or radiation, including chemotherapy, biologic therapy, immunotherapy, or any investigational drug\n- 4. Have had previous interstitial lung disease (ILD), including drug-induced ILD, or active ILD/active radiation pneumonitis\n- 5. Have a mean resting corrected QT interval (QTc) > 470 ms, obtained from triplicate electrocardiograms (ECGs) with QT interval corrected by Fridericia’s method (QTcF)"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 1. Progression Free Survival (PFS) determined by blinded independent central review (BICR)","definition_or_measurement_approach":"PFS determined by blinded independent central review (BICR)"}
  • {"endpoint_text":"- 2. Confirmed overall response rate (ORR) as determined by BICR","definition_or_measurement_approach":"Confirmed ORR as determined by blinded independent central review (BICR)"}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
352
Recruitment Window Months
57
Consent Approach
Informed consent is obtained from participants using subject information sheets and informed consent forms (SIS-ICF) provided in country-specific languages (examples: Italian, Greek, French, Spanish). Country-specific SIS-ICF variants include forms for pregnant participants and pregnant partners and optional biopsy/data privacy modules. No pediatric assent/parental consent procedures are described in the provided materials.

Methods

  • Italy: Site-based recruitment per K1_IT_Recruitment Procedure using HCP letters, HCP factsheets, brochures, IE cards and participant-facing materials in Italian; appointment reminders and thank you letters.
  • Greece: Site-based recruitment per K1_EL_Recruitment Procedure using Greek-language HCP letters, HCP factsheets, brochures, IE cards and participant-facing materials; appointment reminders and thank you letters.
  • France: Recruitment per K1_FR_Recruitment Procedure (Bilingual) including SCOUT recruitment services (SCOUT brochure, SCOUT email communication), HCP letters and factsheets, participant brochures and IE cards in French.
  • Spain: Site-based recruitment per K1_ES_Recruitment Procedure using Spanish-language HCP letters, HCP factsheets, brochures, IE cards and participant-facing materials.

Geography

Total Number Of Sites
22
Total Number Of Participants
36

Italy

Earliest CTIS Part Ii Submission Date
24-10-2025
Latest Decision Or Authorization Date
10-12-2025
Processing Time Days
47
Number Of Sites
3
Number Of Participants
8

Sites

Site Name
Istituto Europeo Di Oncologia S.r.l.
Department Name
Thoracic Oncology Division
Principal Investigator Name
Antonio Passaro
Principal Investigator Email
Antonio.passaro@ieo.it
Contact Person Name
Antonio Passaro
Contact Person Email
Antonio.passaro@ieo.it
Site Name
Centro Di Riferimento Oncologico Di Aviano
Department Name
SOC Oncologia Medica
Principal Investigator Name
Alessandra Bearz
Principal Investigator Email
abearz@cro.it
Contact Person Name
Alessandra Bearz
Contact Person Email
abearz@cro.it
Site Name
Universita' Degli Studi Di Modena E Reggio Emilia
Department Name
SSD Oncologia
Principal Investigator Name
Federica Bertolini
Principal Investigator Email
Bertolini.federica@aou.mo.it
Contact Person Name
Federica Bertolini
Contact Person Email
Bertolini.federica@aou.mo.it

Greece

Earliest CTIS Part Ii Submission Date
05-09-2025
Latest Decision Or Authorization Date
11-12-2025
Processing Time Days
97
Number Of Sites
4
Number Of Participants
8

Sites

Site Name
Thoracic General Hospital Of Athens I Sotiria
Department Name
Oncology Unit, 3rd Department of Internal Medicine andLaboratory
Principal Investigator Name
Konstantinos Syrigos
Principal Investigator Email
ksyrigos.trials@gmail.com
Contact Person Name
Konstantinos Syrigos
Contact Person Email
ksyrigos.trials@gmail.com
Site Name
University General Hospital Attikon General Hospital Of West Attica H Agia Varvara
Department Name
2nd Propaedeutic Internal Medicine Clinic & Research Unit - Oncology Unit
Principal Investigator Name
Amanda Psyrri
Principal Investigator Email
psyrri237@yahoo.com
Contact Person Name
Amanda Psyrri
Contact Person Email
psyrri237@yahoo.com
Site Name
Henry Dunant Hospital Center
Department Name
4th Oncology Department and Clinical Trials Unit
Principal Investigator Name
Ioannis Mountzios
Principal Investigator Email
gmountzios@gmail.com
Contact Person Name
Ioannis Mountzios
Contact Person Email
gmountzios@gmail.com
Site Name
Athens Medical Center S.A.
Department Name
4th Department of Medical Oncology
Principal Investigator Name
Ippokratis Korantzis
Principal Investigator Email
ippokratis.korantzis@gmail.com
Contact Person Name
Ippokratis Korantzis
Contact Person Email
ippokratis.korantzis@gmail.com

France

Earliest CTIS Part Ii Submission Date
27-11-2025
Latest Decision Or Authorization Date
15-12-2025
Processing Time Days
18
Number Of Sites
9
Number Of Participants
14

Sites

Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Pneumology
Principal Investigator Name
Julien Mazieres
Principal Investigator Email
mazieres.j@chu-toulouse.fr
Contact Person Name
Julien Mazieres
Contact Person Email
mazieres.j@chu-toulouse.fr
Site Name
Hospices Civils De Lyon
Department Name
Pulmonology
Principal Investigator Name
Michael Duruisseaux
Principal Investigator Email
michael.duruisseaux@chu-lyon.fr
Contact Person Name
Michael Duruisseaux
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Oncology Medical Department – Oncology Thoracic Unit
Principal Investigator Name
Elvire Pons-Tostivint
Principal Investigator Email
elvire.pons@chu-nantes.fr
Contact Person Name
Elvire Pons-Tostivint
Contact Person Email
elvire.pons@chu-nantes.fr
Site Name
Centre Leon Berard
Department Name
Medical Oncology
Principal Investigator Name
Maurice Perol
Principal Investigator Email
maurice.perol@lyon.unicancer.fr
Contact Person Name
Maurice Perol
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Thoracic Oncology
Principal Investigator Name
Laurent Greillier
Principal Investigator Email
laurent.greillier@ap-hm.fr
Contact Person Name
Laurent Greillier
Contact Person Email
laurent.greillier@ap-hm.fr
Site Name
Hospices Civils De Lyon (Lyon Cedex 04)
Department Name
Pulmonology
Principal Investigator Name
Michael Duruisseaux
Principal Investigator Email
michael.duruisseaux@chu-lyon.fr
Contact Person Name
Michael Duruisseaux
Site Name
Centre Francois Baclesse
Department Name
Department of Pneumology
Principal Investigator Name
Hubert Curcio
Principal Investigator Email
h.curcio@baclesse.unicancer.fr
Contact Person Name
Hubert Curcio
Contact Person Email
h.curcio@baclesse.unicancer.fr
Site Name
Hospices Civils De Lyon (Pierre Benite)
Department Name
Pulmonology
Principal Investigator Name
Michael Duruisseaux
Principal Investigator Email
michael.duruisseaux@chu-lyon.fr
Contact Person Name
Michael Duruisseaux
Site Name
Institut De Cancerologie De L Ouest
Department Name
Medical Oncology
Principal Investigator Name
Ludovic Doucet
Principal Investigator Email
ludovic.doucet@ico.unicancer.fr
Contact Person Name
Ludovic Doucet

Spain

Earliest CTIS Part Ii Submission Date
04-11-2025
Latest Decision Or Authorization Date
12-12-2025
Processing Time Days
38
Number Of Sites
6
Number Of Participants
6

Sites

Site Name
Hospital Universitario Central De Asturias
Department Name
Oncology
Principal Investigator Name
Noemi Villanueva Palicio
Principal Investigator Email
noemivipa@gmail.com
Contact Person Name
Noemi Villanueva Palicio
Contact Person Email
noemivipa@gmail.com
Site Name
Hospital Quironsalud Malaga
Department Name
Oncology
Principal Investigator Name
Manuel Cobo Dols
Principal Investigator Email
manuelcobodols@yahoo.es
Contact Person Name
Manuel Cobo Dols
Contact Person Email
manuelcobodols@yahoo.es
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Oncology
Principal Investigator Name
Oscar José Juan Vidal
Principal Investigator Email
ojjuanv@seom.org
Contact Person Name
Oscar José Juan Vidal
Contact Person Email
ojjuanv@seom.org
Site Name
University Hospital Son Espases
Department Name
Oncology
Principal Investigator Name
Raquel Marsé Fabregat
Principal Investigator Email
raquel.marse@ssib.es
Contact Person Name
Raquel Marsé Fabregat
Contact Person Email
raquel.marse@ssib.es
Site Name
Hospital Clinic De Barcelona
Department Name
Oncology
Principal Investigator Name
Noemí Reguart Aransay
Principal Investigator Email
nreguart@clinic.cat
Contact Person Name
Noemí Reguart Aransay
Contact Person Email
nreguart@clinic.cat
Site Name
Hospital Universitario Y Politecnico La Fe (additional site entry)
Department Name
Oncology
Principal Investigator Name
Oscar José Juan Vidal
Principal Investigator Email
ojjuanv@seom.org
Contact Person Name
Oscar José Juan Vidal
Contact Person Email
ojjuanv@seom.org

Sponsor

Primary sponsor

Full Name
Arrivent Biopharma Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Icon Clinical Research Limited
Responsibilities
Codes [1,10,11,12,13,15]; responsibilities include storage of laboratory samples, medical image and ECG analysis/review, recruitment services (as listed)
Name
PRA Hellas CRO A.E.
Responsibilities
sponsorDuties code 12
Name
Imperial Clinical Research Services International Ltd.
Responsibilities
sponsorDuties code 15 (printing)
Name
Scout Clinical
Responsibilities
sponsorDuties code 15 (patient reimbursement) and recruitment support

Third parties

  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: [7]; contact Joseph.Palladino@3ds.com","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"sponsorDuties code 15 (patient reimbursement)","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Imperial Clinical Research Services International Ltd.","duties_or_roles":"sponsorDuties code 15 (printing)","organisation_type":"Pharmaceutical company"}
  • {"country":"Greece","full_name":"PRA Hellas CRO A.E.","duties_or_roles":"sponsorDuties code 12","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"sponsorDuties code 14","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties codes [1,10,11,12,13,15]; text includes storage of laboratory samples, Medical image and ECG analysis/ review, recruitment services; contact ICONRegulatoryCTIS@iconplc.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties code 15 (eCoA)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Furmonertinib
Active Substance
N-[2-[2-(DIMETHYLAMINO)ETHYL-METHYLAMINO]-5-[[4-(1-METHYLINDOL-3-YL)PYRIMIDIN-2-YL]AMINO]-6-(2,2,2-TRIFLUOROETHOXY)PYRIDIN-3-YL]PROP-2-ENAMIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Investigational (test product, part1 role 'Test')
Starting Dose
240 mg
Dose Levels
240 mg (QD)
Frequency
QD
Maximum Dose
240 mg daily
Investigational Product Name
Osimertinib
Active Substance
OSIMERTINIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Marketing authorisation referenced (EU/1/16/1086/... indicated in product data)
Starting Dose
80 mg
Dose Levels
80 mg (QD)
Frequency
QD
Maximum Dose
80 mg daily
Investigational Product Name
Afatinib
Active Substance
AFATINIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Marketing authorisation referenced (EU/1/13/879/... indicated in product data)
Starting Dose
40 mg
Dose Levels
40 mg (QD)
Frequency
QD
Maximum Dose
40 mg daily

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