Clinical Trials Register

Summary
EudraCT Number:	2019-004773-29
Sponsor's Protocol Code Number:	GO41854
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:	2021-01-25
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

2019-004773-29

A.3

Full title of the trial

A PHASE III, OPEN-LABEL, RANDOMIZED STUDY OF ATEZOLIZUMAB AND TIRAGOLUMAB COMPARED WITH DURVALUMAB IN PATIENTS WITH LOCALLY ADVANCED, UNRESECTABLE STAGE III NON-SMALL CELL LUNG CANCER WHO HAVE NOT PROGRESSED AFTER CONCURRENT PLATINUM-BASED CHEMORADIATION.

STUDIO DI FASE III IN APERTO, RANDOMIZZATO, SULL’USO DI ATEZOLIZUMAB E TIRAGOLUMAB RISPETTO A DURVALUMAB IN PAZIENTI CON CARCINOMA POLMONARE NON A PICCOLE CELLULE IN STADIO III, LOCALMENTE AVANZATO E NON RESECABILE, ANDATI INCONTRO A PROGRESSIONE DOPO CHEMIORADIOTERAPIA CONCOMITANTE A BASE DI PLATINO (SKYSCRAPER-03)

A.3.1

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

A Study of Atezolizumab and Tiragolumab compared with Durvalumab in Patients with Unresectable Stage III Non-Small Cell Lung Cancer who have not Progressed after Concurrent Platinum-based Chemoradiation.

Studio con Atezolizumab e Tiragolumab in confronto con Durvalumab in pazienti con carcinoma polmonare non a piccole cellule allo stadio III non resecabile, non in progressione dopo la concomitante chemioradiazione a base di platino.

A.3.2

Name or abbreviated title of the trial where available

SKYSCRAPER-03

A.4.1

Sponsor's protocol code number

GO41854

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.5.4	Telephone number	000000
B.5.5	Fax number	000000
B.5.6	E-mail	global.rochegenentechtrials@roche.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	Tiragolumab
D.3.2	Product code	[RO7092284/F03-01]
D.3.4	Pharmaceutical form	Concentrate and solvent 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.3.9.3	Other descriptive name	MTIG7192A, anti-TIGIT, aTIGIT, PRO400402, 4.1D3
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: 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	Yes
D.2.1.1.1	Trade name	TECENTRIQ®
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
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: 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	IMFINZI
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
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	NA
D.3.2	Product code	[NA]
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	RO7444835
D.3.9.4	EV Substance Code	SUB176342
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
	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: 4
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	IMFINZI
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
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	NA
D.3.2	Product code	[NA]
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	RO7444835
D.3.9.4	EV Substance Code	SUB176342
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
	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

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

Unresectable Stage III NSCLC is a lung cancer that is in the chest and cannot be surgically removed.

NSCLC di stadio III non resecabile è un tumore polmonare che si trova nel torace e non può essere rimosso chirurgicamente.

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• To evaluate the efficacy of atezolizumab in combination with tiragolumab compared with durvalumab in the intent to treat (ITT) and the programmed death-ligand 1 (PD-L1)-positive populations based on an independent review facility-assessed progression-free survival.

Valutare l’efficacia dell’associazione atezolizumab più tiragolumab rispetto a durvalumab nella popolazione ITT e nella popolazione positiva a PD L1 sulla base della sopravvivenza libera da progressione

E.2.2

Secondary objectives of the trial

• To evaluate the efficacy of atezolizumab plus tiragolumab compared with durvalumab in the ITT and the PD-L1-positive populations based on OS after randomization, Investigator -assessed progression-free survival, , time to death or distant metastasis, confirmed objective response rate, duration of response in patients with confirmed objective response rate, progression-free survival rate, OS rate, time to confirmed deterioration
• To evaluate the safety and tolerability of tiragolumab plus atezolizumab compared with placebo plus durvalumab
• To characterize pharmacokinetics of tiragolumab and atezolizumab
• To evaluate the immune response to tiragolumab plus atezolizumab.

• Valutare l'efficacia di atezolizumab più tiragolumab rispetto a durvalumab nelle popolazioni ITT e PD-L1 positive basandosi su OS dopo randomizzazione, definita come il tempo che intercorre tra la randomizzazione e il decesso per qualsiasi causa
• Valutare la sicurezza e la tollerabilità di tiragolumab più atezolizumab rispetto al placebo più durvalumab
• Caratterizzare la farmacocinetica di tiragolumab e atezolizumab
• Valutare la risposta immunitaria al tiragolumab più atezolizumab.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Age>= 18 years
- Eastern Cooperative Oncology Group Performance Status of 0 or 1
- Histologically or cytologically documented NSCLC with locally advanced unresectable Stage III NSCLC of either squamous or non-squamous histology
- Whole-body positron emission tomography (PET)-CT scan for the purposes of staging, performed prior and within 42 days of the first dose of concurrent chemoradiotherapy (CRT)
- At least two prior cycles of platinum-based chemotherapy concurrent with RT (CRT), which must be completed within 1 to 42 days prior to randomization in the study
- The RT component in the CRT must have been at a total dose of radiation of 60 Gy±10% (54 Gy to 66 Gy) administered by intensity-modulated radiotherapy (preferred) or 3D-conforming technique
- No progression during or following concurrent platinum-based CRT
- Tumor PD-L1 expression, as determined by the investigational Ventana PD-L1 (SP263) CDx assay and documented by central testing of tissue collected prior to the first dose of cCRT
- Adequate hematologic and end-organ function.

• Età ¿ 18 anni
• Performance status ECOG pari a 0 o 1
• NSCLC istologicamente o citologicamente documentato, con NSCLC di stadio III localmente avanzato e non resecabile di istologia squamosa o non squamosa
• Esame di tomografia a emissione di positroni (PET)-TC total body (dalla base del cranio a metà cosce), finalizzato alla stadiazione, eseguito prima ed entro 42 giorni dalla prima dose di CRT concomitante
• Almeno due cicli precedenti di chemioterapia a base di platino concomitanti alla RT (cCRT), che devono essere completati 1-42 giorni prima della randomizzazione nello studio
• La componente RT della cCRT deve aver incluso una dose totale di radiazioni di 60 (¿ 10%) Gy (54¿Gy-66 Gy) somministrate mediante RT a intensità modulata (da preferire) o tecnica conformazionale 3D
• Assenza di progressione durante o dopo la CRT concomitante a base di platino
• Espressione di PD-L1 nel tumore, stabilita mediante saggio sperimentale Ventana PD-L1 (SP263) CDx e documentata mediante analisi centrale di un tessuto tumorale rappresentativo, in tessuto tumorale d’archivio o tessuto fresco ottenuto da biopsia prima della prima dose di cCRT
• Adeguata funzione ematologica e degli organi terminali

E.4

Principal exclusion criteria

- Any history of prior NSCLC
- NSCLC known to have a mutation in the epidermal growth factor mutation and/or an anaplastic lymphoma kinase translocation
- Any evidence of Stage IV disease
- Treatment with sequential CRT for locally advanced NSCLC
- Patients with locally advanced NSCLC who have progressed during or after the definitive concurrent CRT prior to randomization
- Any Grade > 2 unresolved toxicity from previous CRT
- Grade >=2 pneumonitis from prior CRT
- Active or history of autoimmune disease or immune deficiency, history of idiopathic pulmonary fibrosis, organizing pneumonia
- History of malignancy other than NSCLC within 5 years prior to screening
- Prior allogeneic stem cell or solid organ transplantation
- Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening
- Treatment with investigational therapy within 28 days prior to initiation of study treatment
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies
- Any prior Grade >= 3 immune-mediated adverse event or any unresolved Grade > 1 immune-mediated adverse event while receiving any previous immunotherapy agent other than immune checkpoint blockade agents
- Current treatment with anti-viral therapy for hepatitis B virus or hepatitis C virus
- Active EBV infection or known or suspected chronic active EBV infection at Screening
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4, anti-T-cell immunoreceptor with Ig and ITIM domains, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-[antiTNF-alpha]agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressivemedication during study treatment.

• Presenza in anamnesi di NSCLC pregresso
• NSCLC con mutazione nota del gene EGFR o con oncogene di fusione ALK sono esclusi dallo studio:
• Qualsiasi evidenza di malattia in stadio IV
• Trattamento con CRT sequenziale per NSCLC localmente avanzato
• Pazienti con NSCLC localmente avanzato andati incontro a progressione durante o dopo la CRT definitiva concomitante prima della randomizzazione
• Qualsiasi tossicità di grado ¿ 2 non risolta derivante dalla precedente cCRT
• Polmonite di grado ¿ 2 da precedente cCRT
• Malattia autoimmune o deficit immunitario attivi o in anamnesi, inclusi a titolo esemplificativo e non esaustivo miastenia gravis, miosite, epatite autoimmune, lupus eritematoso sistemico, artrite reumatoide, malattia infiammatoria intestinale, sindrome da anticorpi antifosfolipidi, granulomatosi di Wegener, sindrome di Sjögren, sindrome di Guillain-Barré o sclerosi multipla, con le seguenti eccezioni:
• Anamnesi di neoplasie maligne diverse da NSCLC nei 5 anni precedenti lo screening, con l’eccezione delle neoplasie che presentano un rischio trascurabile di metastasi o decesso (per es. con tasso OS a 5 anni ¿ 90%) come carcinoma in situ della cervice, carcinoma cutaneo non melanoma, carcinoma prostatico localizzato, carcinoma mammario duttale in situ o cancro uterino in stadio I che siano stati adeguatamente trattati
• Precedente trapianto allogenico di cellule staminali o di organi solidi
• Positività al test per rilevare gli anticorpi all’antigene del capside virale del virus di Epstein-Barr (EBV) allo screening
• 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¿PD-1 e anti¿PD-L1
• Qualsiasi precedente evento avverso immuno-mediato di grado ¿ 3 o qualsiasi evento avverso immuno-mediato non risolto di grado ¿ 1 durante un precedente trattamento con un agente immunoterapico diverso da agenti di blocco del checkpoint immunitario
• Trattamento con agenti immunostimolatori per via sistemica (inclusi a titolo esemplificativo e non esaustivo interferone e interleuchina-2 [IL-2]) nelle 4 settimane o 5 emivite di eliminazione del farmaco precedenti l’avvio del trattamento in studio (il più lungo tra i due periodi)
• Trattamento con medicinali immunosoppressori per via sistemica (inclusi a titolo esemplificativo e non esaustivo corticosteroidi, ciclofosfamide, azatioprina, metotressato, talidomide e agenti anti-fattore di necrosi antitumorale alfa [anti-TNF-alfa) nelle 2 settimane precedenti l’avvio del trattamento dello studio o necessità prevista di somministrare medicinali immunosoppressori sistemici durante il trattamento dello studio

E.5 End points

E.5.1

Primary end point(s)

1. Independent review facility-assessed Progression Free Survival in ITT and PD-L1 positive populations.

1. Sopravvivenza libera da progressione valutata dalla struttura di revisione indipendente nelle popolazioni positive ITT e PD-L1.

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Up to 90 months.

1. Fino a 90 mesi

E.5.2

Secondary end point(s)

1. Overall survival
2. Investigator -assessed Progression Free Survival
3. Time to death or distant metastasis
4. Confirmed Objective response rate
5. Duration of Response in patients with confirmed ORR
6. Progression Free Survival rate at 12 months, 18 months, and 24 months
7. Overall Survival rate at 12 months, 24 months, 36 months, and 48 months
8. Time to confirmed deterioration
9. Incidence and severity of adverse events
10. Serum concentrations of tiragolumab and atezolizumab at specified timepoints
11. Prevalence and incidence of anti-drug antibodies (ADAs) to tiragolumab and atezolizumab at baseline and during the study.

1. Sopravvivenza globale
2. Sopravvivenza libera da progressione valutata dallo sperimentatore
3. Tempo di morte o metastasi a distanza
4. Tasso di risposta obiettiva confermato
5. Durata della risposta in pazienti con ORR confermato
6. Tasso di sopravvivenza libera da progressione a 12 mesi, 18 mesi e 24 mesi
7. Tasso di sopravvivenza globale a 12 mesi, 24 mesi, 36 mesi e 48 mesi
8. Tempo di deterioramento confermato
9. Incidenza e gravità degli eventi avversi
10. Concentrazioni sieriche di tiragolumab e atezolizumab a intervalli di tempo specifici
11. Prevalenza e incidenza di anticorpi anti-farmaco (ADA) verso tiragolumab e atezolizumab al basale e durante lo studio.

E.5.2.1

Timepoint(s) of evaluation of this end point

1-5. Up to 90 months
6. At 12 months, 18 months, and 24 months
7. At 12 months, 24 months, 36 months, and 48 months
8-9. Up to 90 months
10 and 11. Day 1 of Cycle 1-4,8,10,12 and at treatment discontinuation or completion visit; for tiragolumab: Day 1 of cycle 3.

1-5. Fino a 90 mesi
6. A 12 mesi, 18 mesi e 24 mesi
7. A 12 mesi, 24 mesi, 36 mesi e 48 mesi
8-9. Fino a 90 mesi
10 e 11. Giorno 1 del ciclo 1-4,8,10,12 e all'interruzione del trattamento o visita di completamento; per tiragolumab: giorno 1 del ciclo 3.

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 and Exploratory Biomarker

Immunogenicità e biomarcatore esplorativi

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

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

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

Argentina

Australia

Brazil

Canada

Hong Kong

Israel

Japan

Korea, Republic of

Russian Federation

Taiwan

Thailand

Turkey

Ukraine

United States

Austria

Belgium

Czechia

France

Germany

Greece

Hungary

Italy

Netherlands

Poland

Portugal

Spain

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 will occur when all of the following criteria have been met:
- The required number of deaths for the final analysis of OS has been observed
- The last patient, last visit has occurred.
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.

La fine dello studio sarà quando saranno soddisfatti i seguenti criteri:
- È stato osservato il numero richiesto di decessi per l'analisi finale del sistema operativo
- LVLP
Inoltre, lo sponsor può decidere di interrompere lo studio in qualsiasi momento. Se lo sponsor decide di interrompere lo studio, i pazienti che stanno ancora ricevendo un trattamento di studio o sottoposti a follow-up di sopravvivenza possono essere arruolati in uno studio di estensione.

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:

170

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

138

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

Yes

F.3.3.2

Women of child-bearing potential using contraception

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

308

F.4.2.2

In the whole clinical trial

800

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)

Currently, the Sponsor does not have any plans to provide Roche IMPs (atezolizumab and tiragolumab) or any other study treatments to patients who have completed the study. The Sponsor may evaluate whether to continue providing atezolizumab and tiragolumab in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product, available at the following website:
http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf

Attualmente, lo sponsor non ha in programma di fornire atezolizumab e tiragolumab o altri trattamenti di studio ai pazienti che hanno completato lo studio. Lo sponsor può valutare se continuare a fornire atezolizumab e tiragolumab in conformità con la politica globale di Roche sull'accesso continuato ai medicinali in fase di sperimentazione, disponibile sul 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

2020-09-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-16

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

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
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