Summary
EudraCT Number: 2021-004327-32
Sponsor's Protocol Code Number: D9075C00001
National Competent Authority: Spain - AEMPS 
Clinical Trial Type: EEA CTA
Trial Status: Ongoing
Date on which this record was first entered in the EudraCT database: 2022-07-29
Link: https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-004327-32/ES/

A. Protocol Information
A.1 Member State Concerned: Spain - AEMPS
A.2 EudraCT number: 2021-004327-32
A.3 Full title of the trial: A Phase III, Randomized, Doubleblind, Placebo-controlled, Multicentre, International Study of Durvalumab plus Domvanalimab (AB154) in Participants with Locally Advanced (Stage III), Unresectable Nonsmall Cell Lung Cancer Whose Disease has not Progressed Following Definitive Platinumbased Concurrent Chemoradiation Therapy (PACIFIC-8)
A.3 Full title of the trial (es): Ensayo fase III, aleatorizado, doble ciego, controlado con placebo, multicéntrico e internacional de Durvalumab más Domvanalimab (AB154) en pacientes con cáncer de pulmón no microcítico (estadío III) localmente avanzado e irresecable que no han progresado tras el tratamiento definitivo con quimioradioterapia concurrente basada en platino (PACIFIC-8)
A.3.1 Title of the trial for lay people, in easily understood, i.e. non-technical, language: A Global Study to Assess the Effects of Durvalumab + Domvanalimab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer (PACIFIC 8)
A.3.1 Title of the trial for lay people, in easily understood, i.e. non-technical, language (es): Ensayo internacional para evaluar los efectos de durvalumab + domvanalimab tras la quimiorradioterapia simultánea en pacientes con cáncer de pulmón no microcítico irresecable en estadio III (PACIFIC 8)
A.3.2 Name or abbreviated title of the trial where available: PACIFIC-8
A.4.1 Sponsor's protocol code number: D9075C00001
A.5.2 US NCT (ClinicalTrials.gov registry) number: NCT05211895
A.7 Trial is part of a Paediatric Investigation Plan: No
A.8 EMA Decision number of Paediatric Investigation Plan: 

B. Sponsor Information
Sponsor 1
B.1.1 Name of Sponsor: AstraZeneca AB
B.1.3.4	Country: Sweden
B.3.1 and B.3.2	Status of the sponsor: Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1 Name of organisation providing support: Astrazeneca AB
B.4.2 Country: Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1 Name of organisation: AstraZeneca Farmacéutica Spain, S.A.
B.5.2 Functional name of contact point: Unidad de Investigación Clínica
B.5.3 Address
B.5.3.1 Street Address: C/Serrano Galvache, 56; Parque Norte, Edificio Álamo
B.5.3.2 Town/ city: Madrid
B.5.3.3 Post code: 28033
B.5.3.4 Country: Spain
B.5.4 Telephone number: +34900200444
B.5.6 E-mail: informacionEECC-Spain@astrazeneca.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3 IMP Role: Test
D.2 Status of the IMP to be used in the clinical trial
D.2.1 IMP to be used in the trial has a marketing authorisation: No
D.2.5 The IMP has been designated in this indication as an orphan drug in the Community: No
D.2.5.1 Orphan drug designation number: 
D.3 Description of the IMP
D.3.1 Product name: Durvalumab
D.3.2 Product code: MEDI4736
D.3.4 Pharmaceutical form: Concentrate for solution for infusion
D.3.4.1 Specific paediatric formulation: No
D.3.7 Routes of administration for this IMP:
Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8 INN - Proposed INN: Durvalumab
D.3.9.1 CAS number: 1428935-60-7
D.3.9.2 Current sponsor code: MEDI4736
D.3.10 Strength
D.3.10.1 Concentration unit: mg/ml milligram(s)/millilitre
D.3.10.2 Concentration type: equal
D.3.10.3 Concentration number: 50 
D.3.11 The IMP contains an
D.3.11.1 Active substance of chemical origin: No
D.3.11.2 Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP): Yes
D.3.11.3 Advanced Therapy IMP (ATIMP): No
D.3.11.3.1 Somatic cell therapy medicinal product: No
D.3.11.3.2 Gene therapy medical product: No
D.3.11.3.3 Tissue Engineered Product: No
D.3.11.3.4 Combination ATIMP (i.e. one involving a medical device): No
D.3.11.3.5 Committee on Advanced therapies (CAT) has issued a classification for this product: No
D.3.11.4 Combination product that includes a device, but does not involve an Advanced Therapy: No
D.3.11.5 Radiopharmaceutical medicinal product: No
D.3.11.6 Immunological medicinal product (such as vaccine, allergen, immune serum): No
D.3.11.7 Plasma derived medicinal product: No
D.3.11.8 Extractive medicinal product: No
D.3.11.9 Recombinant medicinal product: Yes
D.3.11.10 Medicinal product containing genetically modified organisms: No
D.3.11.11 Herbal medicinal product: No
D.3.11.12 Homeopathic medicinal product: No
D.3.11.13 Another type of medicinal product: No
D.IMP: 2
D.1.2 and D.1.3 IMP Role: Test
D.2 Status of the IMP to be used in the clinical trial
D.2.1 IMP to be used in the trial has a marketing authorisation: No
D.2.5 The IMP has been designated in this indication as an orphan drug in the Community: No
D.2.5.1 Orphan drug designation number: 
D.3 Description of the IMP
D.3.1 Product name: Domvanalimab
D.3.2 Product code: AB154
D.3.4 Pharmaceutical form: Concentrate for solution for infusion
D.3.4.1 Specific paediatric formulation: No
D.3.7 Routes of administration for this IMP:
Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8 INN - Proposed INN: Domvanalimab
D.3.9.1 CAS number: 2368219-35-4
D.3.9.2 Current sponsor code: AB154
D.3.9.3 Other descriptive name: Domvanalimab
D.3.9.4 EV Substance Code: SUB207237
D.3.10 Strength
D.3.10.1 Concentration unit: mg/ml milligram(s)/millilitre
D.3.10.2 Concentration type: equal
D.3.10.3 Concentration number: 60 
D.3.11 The IMP contains an
D.3.11.1 Active substance of chemical origin: No
D.3.11.2 Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP): Yes
D.3.11.3 Advanced Therapy IMP (ATIMP): No
D.3.11.3.1 Somatic cell therapy medicinal product: No
D.3.11.3.2 Gene therapy medical product: No
D.3.11.3.3 Tissue Engineered Product: No
D.3.11.3.4 Combination ATIMP (i.e. one involving a medical device): No
D.3.11.3.5 Committee on Advanced therapies (CAT) has issued a classification for this product: No
D.3.11.4 Combination product that includes a device, but does not involve an Advanced Therapy: No
D.3.11.5 Radiopharmaceutical medicinal product: No
D.3.11.6 Immunological medicinal product (such as vaccine, allergen, immune serum): No
D.3.11.7 Plasma derived medicinal product: No
D.3.11.8 Extractive medicinal product: No
D.3.11.9 Recombinant medicinal product: Yes
D.3.11.10 Medicinal product containing genetically modified organisms: No
D.3.11.11 Herbal medicinal product: No
D.3.11.12 Homeopathic medicinal product: No
D.3.11.13 Another type of medicinal product: No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1 Is a Placebo used in this Trial? Yes
D.8.3 Pharmaceutical form of the placebo: Solution for injection
D.8.4 Route of administration of the placebo: Intravenous use

E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1 Medical condition(s) being investigated: The target population of interest in this study is participants with locally advanced (Stage III), unresectable NSCLC, whose tumours express PD L1 TC ≥ 1% as assessed by a central reference laboratory using the VENTANA PD-L1 (SP263) IHC assay, and who did not progress after definitive platinum based cCRT.
E.1.1 Medical condition(s) being investigated (es): La población diana de interés en este ensayo está constituida por pacientes con cáncer de pulmón no microcítico (CPNM) en estadio III, localmente avanzado e irresecable, cuyos tumores expresan el gen PD L1 TC ≥1 %, según la evaluación realizada por un laboratorio central de referencia usando el ensayo de IHQ VENTANA PD-L1 (SP263) y que no progresó después de una QRTs con un derivado del platino.
E.1.1.1 Medical condition in easily understood language: Unresectable, locally advanced (Stage III) lung cancer (non-small cell lung cancer) with PD-L1 biomarker expression
E.1.1.1 Medical condition in easily understood language (es): Cáncer de pulmón localmente avanzado e irresecable (estadio III) (cáncer de pulmón no microcítico) con expresión del biomarcador PD-L1
E.1.1.2 Therapeutic area: Diseases [C] - Cancer [C04]
MedDRA Classification
E.1.2 Medical condition or disease under investigation:
E.1.2 Version: 21.1
E.1.2 Level: PT
E.1.2 Classification code: 10061873
E.1.2 Term: Non-small cell lung cancer
E.1.2 System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.3 Condition being studied is a rare disease: No
E.2 Objective of the trial
E.2.1 Main objective of the trial: To demonstrate superiority of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with locally advanced, unresectable NSCLC who have not progressed on prior platinum-based cCRT, with PD-L1 TC ≥ 50%, progression free survival (PFS) assessed by blind independent committee review (BICR).
E.2.1 Main objective of the trial (es): Demostrar la superioridad de la combinación de durvalumab + domvanalimab frente a durvalumab + placebo en participantes con CPNM localmente avanzado irresecable que no han presentado progresión con la QRTs anterior con un derivado del platino, con PD-L1 TC ≥50 %, supervivencia sin enfermedad (SSP) evaluada mediante una
evaluación de comité independiente con enmascaramiento (ECIE).
E.2.2 Secondary objectives of the trial: To demonstrate superiority of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with  TC ≥ 1%, progression free survival (PFS) assessed by Blinded Independent Central Review (BICR).

To demonstrate superiority of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with  TC ≥ 1% or  TC ≥ 50% in the following outcomes:
•	Overall response rate (ORR)
•	Duration of response (DoR)
•	Time to second progression (PFS2)
•	Time to death or distant metastatis (TTDM)
•	Time to First Subsequent Therapy (TFST)
•	PFS at 6, 12, 18 and 24 months 
•	Overall Survival at 24 months (OS 24)
•      Overall Survival (OS)
•	PFS as assessed by investigator 
•	Time to deterioration in pulmonary symptoms
Test the above objectives using an alternative PD-L1 IHC assay, PD-L1 IHC 22C3 pharmDx

PK and immunogenicity of durvalumab and domvanalimab
To assess the safety and tolerability of durvalumab plus domvanalimab as compared to durvalumab plus placebo.
E.2.2 Secondary objectives of the trial (es): Demostrar superioridad de durvalumab+domvanalimab frente a durvalumab+placebo en participantes con un TC≥1%, progresión sin enfermedad(SSP) evaluada mediante una evaluación central independiente con enmascaramiento (ECIE).
Demostrar superioridad de durvalumab+domvanalimab frente a durvalumab+placebo en participantes con TC≥1% o TC≥50% en los siguientes resultados:
•Tasa de respuesta global(TRG)
•Duración de la respuesta(DR)
•Tiempo hasta:
-segunda progresión(SSP2)
-muerte o hasta metástasis a distancia(TTDM)
-primer tratamiento posterior(TPTP)
-deterioro de los síntomas pulmonares
•SSP a los 6,12,18 y 24meses
•Supervivencia global a los 24 meses(SG 24)
•Supervivencia global(SG)
•SSP según la evaluación del investigador
Prueba de los objetivos anteriores utilizando un ensayo IHQ alternativo de PD-L1, como PD-L1 IHC 22C3 pharmDx
FC e inmunogenicidad de durvalumab y domvanalimab
Evaluar la seguridad y tolerabilidad de durvalumab+domvanalimab frente a durvalumab+placebo
E.2.3 Trial contains a sub-study: No
E.3 Principal inclusion criteria: 1. Participant must be ≥ 18 years at the time of screening. 
2. Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease 
3. Provision of a tumour tissue sample obtained prior to CRT
4. Documented tumour PD-L1 status ≥ 1% by central lab
5. Documented EGFR and ALK wild-type status (local or central). 
6. Patients must not have progressed following definitive, platinum-based, concurrent chemoradiotherapy 
7. Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy
8. Participants must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy, to be randomised. Radiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique. 
9. WHO performance status of 0 or 1 at randomization
10. Adequate organ and marrow function
E.3 Principal inclusion criteria (es): 1. El participante debe tener ≥18 años en el momento de la selección.
2. CPNM documentado citológica o histológicamente y que se ha tratado con QTR simultánea como enfermedad localmente avanzada e irresecable (estadio III)
3. Provisión de una muestra tumoral obtenida antes de la QTR
4. Estado PD-L1 ≥1 % del tumor, documentado por el laboratorio central
5. Estado documentado de TFGe y ALK de tipo natural (local o central).
6. Los pacientes no deben haber presentado progresión tras quimiorradioterapia simultánea definitiva con un derivado del platino
7. Los participantes deben haber recibido al menos dos ciclos de quimioterapia con un derivado del platino, simultáneamente con radioterapia
8. Los participantes deben haber recibido una dosis total de radiación de 60 Gy±10 % (de 54 Gy a 66 Gy) como parte de la quimiorradioterapia, para la aleatorización. La radioterapia se debe administrar como RT de intensidad modulada (preferida) o como técnica de conformación 3D.
9. Estado funcional de la OMS de 0 o 1 en el momento de la aleatorización
10. Función orgánica y medular adecuada
E.4 Principal exclusion criteria: Participants are excluded from the study if any of the following criteria apply:
1. History of another primary malignancy except for malignancy treated with curative intent with no known active disease > 5 years before the first dose of study intervention and of low potential risk for recurrence, basal cell carcinoma of the skin, squamous cell carcinoma of the skin or lentigo maligna that has undergone potentially curative therapy, adequately treated carcinoma in situ or Ta tumours treated with curative intent and without evidence of disease.
2. Mixed small cell and non-small cell lung cancer histology.
3. Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
4. Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
5. Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy (excluding alopecia). 
6. Participants with ≥grade 2 pneumonitis from prior chemoradiation therapy.
7. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, ILD, pleural effusion, or pulmonary fibrosis diagnosed in the past 6 months prior to randomization. 
8. Active or prior documented autoimmune or inflammatory disorders (with exceptions)
9. Active EBV infection, or known or suspected chronic active EBV infection at screening
10. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.

Reproduction
11. Negative pregnancy test (serum) for WOCBP:
12. Female participants must be 1 year post menopausal, surgically sterile, or using 1 highly effective form of birth control 
13. Male participants who intend to be sexually active with a WOCBP must be surgically sterile or using an acceptable method of contraception
E.4 Principal exclusion criteria (es): Los participantes quedan excluidos del ensayo si se aplica alguno de los siguientes criterios:
1. Antecedentes de cualquier otra neoplasia maligna primaria excepto las neoplasias malignas tratadas con intención terapéutica sin cáncer activo conocido durante >5 años antes de la primera dosis de intervención del ensayo y bajo potencial de riesgo de recidiva, carcinoma de células basales de la piel, carcinoma de células escamosas de la piel o lentigo maligno que se ha sometido a tratamiento potencialmente terapéutico, carcinoma tratado adecuadamente in situ o tumores Ta tratados con intención terapéutica y sin evidencia de cáncer.
2. Histología mixta de cáncer microcítico y no microcítico.
3. Los participantes que recibirán una quimiorradioterapia secuencial (sin incluir la inducción) para el CPNM irresecable localmente avanzado (estadio III).
4. Los participantes con CPNM localmente avanzado irresecable (estadio III) que han progresado durante la QRTs con un derivado del platino.
5. Cualquier toxicidad no resuelta con CTCAE de Grado >2 antes de la quimiorradioterapia (excluida la alopecia).
6. Los participantes con neumonitis de grado ≥2 a partir de la quimiorradioterapia anterior.
7. Antecedentes de fibrosis pulmonar idiopática, neumonía organizada, neumonitis inducida por fármacos, o neumonitis idiopática, o evidencia de neumonitis activa, EPI, efusión pleural o fibrosis pulmonar diagnosticada en los últimos 6 meses anteriores a la aleatorización.
8. Trastornos autoinmunitarios o inflamatorios activos o previamente documentados (con excepciones).
9. Infección por VEB activa, o bien infección crónica conocida o presunta por VEB.
10. Uso actual o anterior de medicamentos inmunodepresores en los 14 días anteriores a la primera dosis de durvalumab.

Reproducción
11. Prueba de embarazo negativa (suero) en mujeres en edad fértil:
12. Las mujeres participantes deben llevar al menos 1 año en menopausia, presentar esterilidad por razones quirúrgicas o bien usar un método de control de la natalidad muy eficaz
13. Los varones participantes que tengan intención de ser activos sexualmente con una mujer en edad fértil deben presentar esterilidad por razones quirúrgicas o bien usar un método aceptable de anticoncepción
E.5 End points
E.5.1 Primary end point(s): Progression Free Survival (PFS) using Blinded Independent Central Review (BICR) assessment according to RECIST 1.1 with participants with PD-L1 TC>=50%.
E.5.1 Primary end point(s) (es): La supervivencia sin progresión (SSP) usando una evaluación central independiente con enmascaramiento (ECIE) según RECIST 1.1 con participantes que presentan un PD-L1 TC ≥50 %.
E.5.1.1 Timepoint(s) of evaluation of this end point: PFS will be evaluated every 8 weeks (±7 days) from randomisation through 48 weeks, and q12w (± 7 days) thereafter until RECIST 1.1 defined radiological progression, plus 1 or more follow-up scans.
E.5.1.1 Timepoint(s) of evaluation of this end point (es): La SSP se evaluará cada 8 semanas (±7 días) desde la aleatorización hasta la semana 48, y c12s (±7 días) posteriormente, hasta la progresión radiológica definida según RECIST 1.1, más 1 o más exploraciones de seguimiento.
E.5.2 Secondary end point(s): PFS measured by hazard ratio (HR), in participants with PD-L1 TC ≥ 1% as assessed by BICR.

Comparison of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with  TC ≥ 1% or  TC ≥ 50% in the following outcomes 

1. Overall Survival (OS)
2. PFS assessment by investigator according to RECIST 1.1
3. PFS6, PFS12, PFS18, PFS24
4. Overall Survival at 24 months (OS 24)
5. Objective response rate (ORR) using BICR assessment according to RECIST 1.1.
6. Duration of response (DoR) using BICR assessment according to RECIST 1.1
7. Time from randomization to second progression (PFS2)
7. Time from randomization until the first date of distant metastasis or death in the absence o distant metastasis (TTDM).
9. Time to first subsequent therapy (TFST)
10. The pharmacokinetics (PK) of durvalumab and domvanalimab as determined by concentration.
11. The immunogenicity of Durvalumab and domvanalimab as assessed by presence of anti-drug antibodies (ADAs)
12. Time to First Confirmed Deterioration (TTFCD) in pulmonary symptoms  measured by the NSCLC-SAQ.
13. Test the above objectives using an alternative PD-L1 IHC assay, PD-L1 IHC 22C3 pharmDx
E.5.2 Secondary end point(s) (es): SSP medida por el cociente de riesgos instantáneos (CRI) en participantes con un PD-L1 TC ≥1 %, según la evaluación ECIE.

Comparación de durvalumab más domvanalimab frente a durvalumab más placebo en participantes con TC ≥1 % o TC ≥50 % en los siguientes resultados

1. Supervivencia global (SG)
2. SSP según la evaluación del investigador según RECIST 1.1
3. SSP6, SSP12, SSP18, SSP24
4. Supervivencia global a los 24 meses (SG 24)
5. Tasa de respuesta objetiva (TRO) usando la evaluación ECIE según RECIST 1.1.
6. Duración de la respuesta (DR) usando la evaluación ECIE según RECIST 1.1
7. Tiempo desde la aleatorización hasta la segunda progresión (SSP2)
7. Tiempo transcurrido desde la aleatorización hasta la primera fecha de metástasis a distancia o muerte en ausencia de metástasis a distancia (TTDM).
9. Tiempo hasta el primer tratamiento posterior (TPTP)
10. La farmacocinética (FC) de durvalumab y domvanalimab según se determina por la concentración.
11. La inmunogenicidad de durvalumab y domvanalimab tal y como se evalúe por la presencia de anticuerpos antifármaco (AAF)
12. Tiempo hasta el primer deterioro confirmado (TTFCD) en síntomas pulmonares medidos por el NSCLC-SAQ.
13. Prueba de los objetivos anteriores utilizando un ensayo IHQ alternativo de PD-L1, como PD-L1 IHC 22C3 pharmDx
E.5.2.1 Timepoint(s) of evaluation of this end point: PFS will be evaluated every 8 weeks (±7 days) from randomisation through 48 weeks, and q12w (± 7 days) thereafter until RECIST 1.1 defined radiological progression, plus 1 or more follow-up scans. 

ORR, DoR, PFS by investigator, PFS2, PFS6, PFS12, PFS18, PFS24, TTDM, TFST, TTFCD, up to approximately 8 years after first patient randomized

OS and OS24, up to approximately 8 years after first patient randomized.

ADA and PK: from date of randomization to approximately 12 weeks after last IP dose.
E.5.2.1 Timepoint(s) of evaluation of this end point (es): La SSP se evaluará cada 8 semanas (±7 días) desde la aleatorización hasta la semana 48, y c12s (±7 días) posteriormente, hasta la progresión radiológica definida según RECIST 1.1, más 1 o más exploraciones de seguimiento.

TRO, DR, SSP según el investigador, SSP2, SSP6, SSP12, SSP18, SSP24, TTDM, TPTP, TTFCD, hasta pasados aproximadamente 8 años desde el primer paciente aleatorizado

SG y SG24 hasta pasados aproximadamente 8 años desde el primer paciente aleatorizado.

AAF y FC: desde la fecha de aleatorización hasta aproximadamente 12 semanas desde la última dosis IP.
E.6 and E.7 Scope of the trial
E.6 Scope of the Trial
E.6.1 Diagnosis: No
E.6.2 Prophylaxis: No
E.6.3 Therapy: Yes
E.6.4 Safety: Yes
E.6.5 Efficacy: Yes
E.6.6 Pharmacokinetic: Yes
E.6.7 Pharmacodynamic: No
E.6.8 Bioequivalence: No
E.6.9 Dose response: No
E.6.10 Pharmacogenetic: Yes
E.6.11 Pharmacogenomic: Yes
E.6.12 Pharmacoeconomic: No
E.6.13 Others: Yes
E.6.13.1 Other scope of the trial description: Tolerability 
Symptoms and Health-related quality of life
E.6.13.1 Other scope of the trial description (es): Tolerabilidad
Síntomas y calidad de vida relacionada con la salud
E.7 Trial type and phase 
E.7.1 Human pharmacology (Phase I): No
E.7.1.1 First administration to humans: No
E.7.1.2 Bioequivalence study: No
E.7.1.3 Other: No
E.7.1.3.1 Other trial type description: 
E.7.2 Therapeutic exploratory (Phase II): No
E.7.3 Therapeutic confirmatory (Phase III): Yes
E.7.4 Therapeutic use (Phase IV): No
E.8 Design of the trial
E.8.1 Controlled: Yes
E.8.1.1 Randomised: Yes
E.8.1.2 Open: No
E.8.1.3 Single blind: No
E.8.1.4 Double blind: Yes
E.8.1.5 Parallel group: No
E.8.1.6 Cross over: No
E.8.1.7 Other: No
E.8.2 Comparator of controlled trial
E.8.2.1 Other medicinal product(s): No
E.8.2.2 Placebo: Yes
E.8.2.3 Other: No
E.8.2.4 Number of treatment arms in the trial: 2
E.8.3 The trial involves single site in the Member State concerned: No
E.8.4 The trial involves multiple sites in the Member State concerned: Yes
E.8.4.1 Number of sites anticipated in Member State concerned: 6
E.8.5 The trial involves multiple Member States: Yes
E.8.5.1 Number of sites anticipated in the EEA: 57
E.8.6 Trial involving sites outside the EEA
E.8.6.1 Trial being conducted both within and outside the EEA: Yes
E.8.6.2 Trial being conducted completely outside of the EEA: No
E.8.6.3 If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned:
Brazil
Chile
China
India
Japan
Korea, Republic of
Malaysia
Mexico
Philippines
South Africa
Taiwan
United States
France
Poland
Romania
Spain
Germany
Greece
Belgium
Hungary
Norway
Russian Federation
Turkey
Ukraine
United Kingdom
E.8.7 Trial has a data monitoring committee: Yes
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial: The end of study is defined as the date of the last visit for the last participant in the study globally. 
A participant is considered to have completed the study if he/she has completed all phases of the study including the last expected visit. Participants may be withdrawn from the study if the study itself is stopped. The study may be stopped if, in the judgement of AstraZeneca, participants are placed at undue risk because of clinically significant findings.
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial (es): El final del ensayo se define como la fecha de la última visita del último paciente del ensayo, globalmente. Se considera que un paciente ha terminado el ensayo en caso de que haya completado todas las visitas del ensayo. Los pacientes se pueden retirar del ensayo si este se interrumpe. El ensayo se puede interrumpir si, a juicio de AstraZeneca, los pacientes se encuentran en una situación de riesgo por encontrarse hallazgos clínicamente significativos.
E.8.9 Initial estimate of the duration of the trial
E.8.9.1 In the Member State concerned years: 6
E.8.9.1 In the Member State concerned months: 10
E.8.9.1 In the Member State concerned days: 7
E.8.9.2 In all countries concerned by the trial years: 7
E.8.9.2 In all countries concerned by the trial months: 8
E.8.9.2 In all countries concerned by the trial days: 0

F. Population of Trial Subjects
F.1 Age Range
F.1.1 Trial has subjects under 18: No
F.1.1.1 In Utero: No
F.1.1.2 Preterm newborn infants (up to gestational age < 37 weeks): No
F.1.1.3 Newborns (0-27 days): No
F.1.1.4 Infants and toddlers (28 days-23 months): No
F.1.1.5 Children (2-11years): No
F.1.1.6 Adolescents (12-17 years): No
F.1.2 Adults (18-64 years): Yes
F.1.2.1 Number of subjects for this age range: 942
F.1.3 Elderly (>=65 years): Yes
F.1.3.1 Number of subjects for this age range: 628
F.2 Gender
F.2.1 Female: Yes
F.2.2 Male: Yes
F.3 Group of trial subjects
F.3.1 Healthy volunteers: No
F.3.2 Patients: Yes
F.3.3 Specific vulnerable populations: Yes
F.3.3.1 Women of childbearing potential not using contraception : No
F.3.3.2 Women of child-bearing potential using contraception: Yes
F.3.3.3 Pregnant women: No
F.3.3.4 Nursing women: No
F.3.3.5 Emergency situation: No
F.3.3.6 Subjects incapable of giving consent personally: Yes
F.3.3.6.1 Details of subjects incapable of giving consent: If yes a legal representative may provide consent on behalf of a subject incapable of giving consent personally, where permitted by local regulations.
F.3.3.6.1 Details of subjects incapable of giving consent (es): En este caso, un representante legal puede proporcionar consentimiento en nombre de un sujeto incapaz de ofrecer el consentimiento personalmente, cuando lo permita la regulación local.
F.3.3.7 Others: No
F.4 Planned number of subjects to be included
F.4.1 In the member state: 21
F.4.2 For a multinational trial
F.4.2.1 In the EEA: 455
F.4.2.2 In the whole clinical trial: 1570
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition): Treatment plan after the end of participation in the trial is not different from the expected normal treatment of Unresectable Non small Cell Lung Cancer.
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition) (es): El plan de tratamiento una vez terminada la participación en el ensayo no es diferente del tratamiento normal esperado para el caso del cáncer de pulmón no microcítico irresecable.

G. Investigator Networks to be involved in the Trial


N. Review by the Competent Authority or Ethics Committee in the country concerned
N. Competent Authority Decision: Authorised
N. Date of Competent Authority Decision: 2022-09-07
N. Ethics Committee Opinion of the trial application: Favourable
N. Ethics Committee Opinion: Reason(s) for unfavourable opinion:
N. Date of Ethics Committee Opinion: 2022-08-30

P. End of Trial
P. End of Trial Status: Ongoing