Clinical Trials Register

Summary
EudraCT Number:	2020-002851-39
Sponsor's Protocol Code Number:	BO42592
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-05-20
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-002851-39

A.3

Full title of the trial

A PHASE II, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF TIRAGOLUMAB IN COMBINATION WITH ATEZOLIZUMAB PLUS PEMETREXED AND CARBOPLATIN/CISPLATIN VERSUS PEMBROLIZUMAB PLUS PEMETREXED AND CARBOPLATIN/CISPLATIN IN PATIENTS WITH PREVIOUSLY UNTREATED ADVANCED NON-SQUAMOUS NON-SMALL CELL LUNG CANCER.

STUDIO DI FASE II, RANDOMIZZATO, IN DOPPIO CIECO, PLACEBO CONTROLLATO SULL’USO DI TIRAGOLUMAB IN ASSOCIAZIONE AD ATEZOLIZUMAB PIÙ PEMETREXED E CARBOPLATINO/CISPLATINO RISPETTO A PEMBROLIZUMAB PIÙ PEMETREXED E CARBOPLATINO/CISPLATINO IN PAZIENTI CON CARCINOMA POLMONARE NON A PICCOLE CELLULE NON SQUAMOSO IN STADIO AVANZATO E NON PRETRATTATO

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Study of Tiragolumab in Combination with Atezolizumab Plus Pemetrexed and Carboplatin/Cisplatin versus Pembrolizumab Plus Pemetrexed and Carboplatin/Cisplatin in Patients with Previously Untreated Advanced Non-Squamous Non-Small Cell Lung Cancer.

STUDIO SULL’USO DI TIRAGOLUMAB IN ASSOCIAZIONE AD ATEZOLIZUMAB PIÙ PEMETREXED E CARBOPLATINO/CISPLATINO RISPETTO A PEMBROLIZUMAB PIÙ PEMETREXED E CARBOPLATINO/CISPLATINO IN PAZIENTI CON CARCINOMA POLMONARE NON A PICCOLE CELLULE NON SQUAMOSO IN STADIO AVANZATO E NON PRETRATTATO

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

BO42592

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	F. HOFFMANN - LA ROCHE LTD.
B.1.3.4	Country	Switzerland
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	F. Hoffmann-La Roche Ltd
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Genentech Inc. c/o F. Hoffmann-La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.6	E-mail	global.rochegenentechtrials@roche.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Pemetrexed
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly Nederland B.V. - EU/1/04/1034/002
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Pemetrexed
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Powder 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	PEMETREXED
D.3.9.1	CAS number	137281-23-3
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB09655MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	No
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	Comparator
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	Yes
D.2.1.1.1	Trade name	CISPLATINO TEVA ITALIA - 1MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO IN VETRO DA 100 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	TEVA ITALIA S.R.L.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Cisplatin
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Concentrate for solution for injection/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	CISPLATIN
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB07483MIG
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	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	No
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: 3
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	CARBOPLATINO AHCL - 10 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO DI VETRO DA 15 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ACCORD HEALTHCARE S.L.U.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Carboplatin
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Concentrate for solution for injection/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	CARBOPLATINO
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB06614MIG
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	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	No
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: 4
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	tiragolumab
D.3.2	Product code	[RO7092284/F03-01]
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	TIRAGOLUMAB
D.3.9.1	CAS number	1918185-84-8
D.3.9.2	Current sponsor code	RO7092284
D.3.9.4	EV Substance Code	SUB197861
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
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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: 5
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	Yes
D.2.1.1.1	Trade name	TECENTRIQ®
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH - Mark.Auth. EU/1/17/1220/001
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Atezolizumab
D.3.2	Product code	[RO5541267]
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	ATEZOLIZUMAB
D.3.9.2	Current sponsor code	RO5541267
D.3.9.4	EV Substance Code	SUB178312
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
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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: 6
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Keytruda
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B.V., The Netherlands Aut.EU/1/15/1024/002
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	pembrolizumab
D.3.2	Product code	[RO7223188]
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	Pembrolizumab
D.3.9.1	CAS number	1374853-91-4
D.3.9.2	Current sponsor code	RO7223188
D.3.9.4	EV Substance Code	SUB167136
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	25
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
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Concentrate for solution for infusion
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

Non-small cell lung cancer (NSCLC)

CARCINOMA POLMONARE NON A PICCOLE CELLULE

E.1.1.1

Medical condition in easily understood language

Non-small cell lung cancer is cancer of the lung which is not of the small cell carcinoma (oat cell carcinoma) type.

carcinoma polmonare non a piccole cellule

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.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10079440
E.1.2	Term	Non-squamous 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

E.2 Objective of the trial

E.2.1

Main objective of the trial

L’obiettivo di efficacia primario di questo studio è valutare l’efficacia di tiragolumab in associazione ad atezolizumab più pemetrexed e carboplatino/cisplatino (Braccio A) rispetto a placebo in associazione a pembrolizumab più pemetrexed e carboplatino/cisplatino (Braccio B) sulla base dei seguenti endpoint:
• Tasso di risposta obiettiva (Objective Response Rate, ORR)
• Sopravvivenza libera da progressione (Progression-Free Survival, PFS), definita come il tempo che intercorre tra la randomizzazione e la prima registrazione di una progressione della malattia o il decesso per qualsiasi causa (a seconda del caso che si verifica prima), secondo la valutazione dello sperimentatore basata sui criteri RECIST v. 1.1.

E.2.2

Secondary objectives of the trial

• To evaluate the efficacy of tiragolumab in combination with atezolizumab plus pemetrexed and carboplatin/cisplatin (Arm A) compared with placebo in combination with pembrolizumab plus pemetrexed and carboplatin/cisplatin (Arm B) on the basis of overall survival, duration of response and time to confirmed deterioration in patient-reported physical functioning and global health status/quality of life (GHS/QoL), and in patient-reported lung cancer symptoms for cough, dyspnea (a multi-item subscale), and chest pain
• To evaluate the safety of tiragolumab in combination with atezolizumab plus pemetrexed and carboplatin/cisplatin (Arm A) compared with placebo in combination with pembrolizumab plus pemetrexed and carboplatin/cisplatin (Arm B)
• To characterize the pharmacokinetics of tiragolumab and atezolizumab
• To evaluate the immune response to tiragolumab and atezolizumab.

L’obiettivo di efficacia secondario è valutare l’efficacia di tiragolumab in associazione ad atezolizumab più pemetrexed e carboplatino/cisplatino (Braccio A) rispetto a placebo in associazione a pembrolizumab più pemetrexed e carboplatino/cisplatino (Braccio B) sulla base dei seguenti endpoint:
• Sopravvivenza globale (OS), Durata della risposta,Tempo al deterioramento confermato delle funzioni fisiche e dello stato di salute generale/qualità di vita (Qol), sintomi riferiti dal paziente di tosse, dispnea e dolore toracico
L’obiettivo di sicurezza è valutare la sicurezza di tiragolumab in associazione ad atezolizumab più pemetrexed e carboplatino/cisplatino (Braccio A) rispetto a placebo in associazione a pembrolizumab più pemetrexed e carboplatino/cisplatino (Braccio B)
L’obiettivo di farmacocinetica (PK) è caratterizzare la farmacocinetica di tiragolumab e atezolizumab
L’obiettivo di immunogenicità è valutare la risposta immunitaria all’associazione tiragolumab più atezolizumab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Histologically or cytologically documented locally advanced unresectable or metastatic non-squamous NSCLC
• No prior systemic treatment for metastatic non-squamous NSCLC
• Known tumor PD-L1 status
• Measurable disease, as defined by RECIST v1.1
• Life expectancy >= 12 weeks
• Adequate hematologic and end-organ function
• Negative HIV test at screening
• Serology test negative for active hepatitis B virus or active hepatitis C virus at screening

•Firma del modulo di consenso informato
•Età maggiore o uguale a18 anni al momento della firma del modulo di consenso informato
•Capacità, secondo il giudizio dello sperimentatore, di rispettare il protocollo dello studio
•Performance status ECOG pari a 0 o 1
•NSCLC non squamoso, localmente avanzato e non resecabile o metastatico, con documentazione istologica o citologica
•Nessun precedente trattamento sistemico per NSCLC non squamoso
•Stato di PD L1 tumorale
•Malattia misurabile, definita secondo i criteri RECIST v 1.1
•Aspettativa di vita maggiore o uguale a 12 settimane
•Adeguata funzione ematologica e degli organi terminali
•Risultato negativo del test per l’HIV allo screening
• Risultato positivo del test degli anticorpi di superficie dell’epatite B (HBsAb) allo screening oppure negatività per HBsAb allo screening associato a uno dei seguenti parametri:
– Negatività per l’anticorpo core totale dell’epatite B (HBcAb).
– Test HBcAb totale positivo, seguito da un test negativo (secondo la definizione del laboratorio locale) del DNA del virus dell’epatite B (HBV).
• Risultato negativo del test degli anticorpi dell’epatite C (HCV) allo screening oppure risultato positivo del test degli anticorpi HCV, seguito da risultato negativo del test HCV-RNA allo screening

E.4

Principal exclusion criteria

• Patients with NSCLC which harbors a mutation in the EGFR gene or an ALK fusion oncogene
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active peumonitis
• History of malignancy other than NSCLC within 5 years prior to randomization, with the exception of malignancies with a negligible risk of metastasis or death
• Severe infection within 4 weeks prior to initiation of study treatment
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment.

-NSCLC con nota mutazione del gene EGFR o nell’oncogene di fusione ALK
-Sottotipo di NSCLC: carcinoma simil-linfoepitelioma del polmone
-Metastasi del sistema nervoso centrale (SNC) sintomatiche, non trattate o in progressione attiva
-Malattia autoimmune o deficit immunitario attivi o in anamnesi
-Presenza in anamnesi di fibrosi polmonare idiopatica, polmonite in via di organizzazione, polmonite indotta da farmaci o polmonite idiopatica oppure evidenza di polmonite attiva
-Anamnesi di neoplasie maligne diverse da NSCLC nei 5 anni precedenti la randomizzazione, con l’eccezione delle neoplasie che presentano un rischio trascurabile di metastasi o decesso
-Grave infezione nelle 4 settimane precedenti l’inizio del trattamento in studio
- Trattamento con una terapia sperimentale nei 28 giorni precedenti l’inizio trattamento dello studio
-Precedente trattamento con agonisti di CD137 o con terapie di blocco del checkpoint immunitario, inclusi anticorpi terapeutici anti proteina 4 associata al linfocita T citotossico, anti¿TIGIT, anti¿PD1 e anti¿PD-L1
-Trattamento con agenti immunostimolatori per via sistemica nelle 4 settimane o 5 emivite di eliminazione del farmaco precedenti l’avvio del trattamento in studio (il più lungo tra i due periodi)

E.5 End points

E.5.1

Primary end point(s)

1. Investigator-Assessed Confirmed Objective Response Rate (ORR)
2. Investigator-Assessed Progression-free survival (PFS).

• Tasso di risposta obiettiva (Objective Response Rate, ORR) confermato secondo il giudizio dello sperimentatore
• Sopravvivenza libera da progressione (Progression-Free Survival, PFS), secondo la valutazione dello sperimentatore

E.5.1.1

Timepoint(s) of evaluation of this end point

1-2. Up to 5 years.

1-2. Fino a 5 anni.

E.5.2

Secondary end point(s)

1. Overall survival
2. Duration of response for patients with a confirmed objective response, defined as the time from first occurrence of a confirmed objective response to disease progression or death from any cause (whichever occurs first)
3. Time to confirmed deterioration (TTCD) in patient-reported physical functioning and global health status/quality of life (GHS/QoL), as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core (QLQ-C30), and in patient-reported lung cancer symptoms for cough, dyspnea (a multi-item subscale), and chest pain, as measured through the use of the EORTC Quality-of-Life Questionnaire Lung Cancer Module (QLQ-LC13)
4. Percentage of Participants with Adverse Events (AEs)
5. Frequency of patients’ response of the degree they are troubled with treatment symptoms, as assessed through use of the single-item EORTC IL46
6. Serum concentrations of tiragolumab and atezolizumab
7. Percentage of participants with anti-drug antibodies (ADAs) to tiragolumab
8. Percentage of participants with ADAs to atezolizumab.

1 Sopravvivenza globale
2 Durata della risposta nei pazienti con risposta obiettiva confermata, definita come il tempo che intercorre tra la prima registrazione di una risposta obiettiva confermata e la progressione della malattia o il decesso per qualsiasi causa (a seconda del caso che si verifica prima)
3 Tempo al deterioramento confermato delle funzioni fisiche riferite dal paziente e dello stato di salute generale/qualità di vita misurato attraverso il questionario Quality of Life Questionnaire Core 30 (QLQ-C30) della European Organisation for Research and Treatment of Cancer (EORTC), dei sintomi del tumore polmonare riferiti dal paziente di tosse, dispnea (sottoscala a più voci) e dolore toracico, misurati attraverso il questionario Quality-of-Life Questionnaire Lung Cancer Module (QLQ LC13) dell’EORTC.
4. Incidenza e gravità degli eventi avversi
5.Frequenza della risposta dei pazienti sul grado di fastidio provocato dal trattamento dei sintomi, valutato in base all’elenco di 46 voci dell’EORTC (IL46).
6 Concentrazioni sieriche di tiragolumab e atezolizumab
7 Prevalenza di anticorpi anti farmaco (Anti-Drug Antibody, ADA) diretti contro tiragolumab al basale e incidenza di ADA diretti contro tiragolumab
8 Prevalenza di ADA diretti contro atezolizumab al basale e incidenza di ADA diretti contro atezolizumab durante lo studio.

E.5.2.1

Timepoint(s) of evaluation of this end point

1-5. Up to 5 years
6-8. Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16 and at treatment discontinuation (up to 5 years).

1-5. Fino a 5 anni
6-8 Giorno 1 del Ciclo 1,2,3,4,8,12,16 e alla discontinuazione del trattamento (fino a 5 anni)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity

Immunogenicità

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Information not present in EudraCT

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

Canada

Hong Kong

Korea, Republic of

New Zealand

Taiwan

United States

Belgium

France

Germany

Italy

Spain

Switzerland

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 this study will occur when the last data required for all study analyses are collected.
In addition, the Sponsor may decide to terminate the study at any time. If the Sponsor decides to terminate the study, patients who are still receiving study treatment or undergoing survival follow-up may be enrolled in an extension study and/or offered continued access to study treatment through a post-trial access program.

Lo studio terminerà all'avvenuta raccolta dell'ultimo dato richiesto per tutte le analisi dello studio.
Il promotore potrà inoltre decidere di interrompere lo studio in qualsiasi momento.
Se il Promotore deciderà di interrompere lo studio, i pazienti che stanno ancora ricevendo il trattamento di studio o sono in follow-up potranno essere arruolati in uno studio di estensione e/o potranno avere accesso continuato al trattamento di studio attraverso un programma di accesso post-studio.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

200

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)

Patients may be eligible to receive study drug as part of an extension study, as described in Section 3.2 or the Sponsor may offer continued access to Roche IMPs (tiragolumab and atezolizumab) after completing the study. The Roche Global Policy on Continued Access to Investigational Medicinal Product is available at the following website:
http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf

I pazienti eligibili potranno ricevere il farmaco di studio tramite uno studio di estensione, o lo sponsor potrà offrire un accesso continuo al trattamento di studio per gli IMP Roche (tiragolumab and atezolizumab) dopo il completamento dello studio, in conformità con la politica globale di Roche disponibile al seguente sito web: http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-12-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-12-22

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

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Orphan Designation Number:
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