Clinical Trials Register

Summary
EudraCT Number:	2020-004091-18
Sponsor's Protocol Code Number:	D6132C00001
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-05-24
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2020-004091-18

A.3

Full title of the trial

A Phase II Multicenter, Open-Label, Single Arm Study to
Determine the Efficacy, Safety and Tolerability of AZD2811 and
Durvalumab Combination as Maintenance Therapy After
Induction with Platinum-Based Chemotherapy Combined with
Durvalumab, for the First-Line Treatment of Patients with
Extensive Stage Small-Cell Lung Cancer.

Wieloośrodkowe badanie fazy II prowadzone metodą otwartej próby w ramach pojedynczego ramienia, mające na celu ocenę skuteczności, bezpieczeństwa i tolerancji AZD2811 podawanego w skojarzeniu z durwalumabem, w leczeniu podtrzymującym po chemioterapii indukcyjnej na bazie platyny w połączeniu z durwalumabem, w ramach pierwszej linii leczenia pacjentów z drobnokomórkowym rakiem płuca w stadium rozległym (TAZMAN)

A.3.1

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

A study investigating what potential benefits adding AZD2811 might have to the current standard of care maintenance therapy of durvalumab in patients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC) who have not had any treatment yet for their cancer.

Badanie oceniające, jakie potencjalne korzyści może mieć dodanie AZD2811 do obecnego standardu leczenia podtrzymującego durwalumabem u pacjentów z drobnokomórkowym rakiem płuca w stadium rozległym (ES- SCLC), którzy nie byli jeszcze leczeni na raka

A.3.2

Name or abbreviated title of the trial where available

TAZMAN

A.4.1

Sponsor's protocol code number

D6132C00001

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	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 AB
B.5.2	Functional name of contact point	Information Center
B.5.3	Address:
B.5.3.1	Street Address	n/a
B.5.3.2	Town/ city	n/a
B.5.3.3	Post code	n/a
B.5.3.4	Country	United States
B.5.6	E-mail	information.center@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	AZD2811 suspension for constitution for infusion
D.3.2	Product code	AZD2811
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	AZD2811
D.3.9.1	CAS number	722544-51-6
D.3.9.2	Current sponsor code	AZD2811
D.3.10	Strength
D.3.10.1	Concentration unit	mg/l milligram(s)/litre
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	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	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	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
	The IMP is a:
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

First-line patients with extensive disease small-cell lung cancer (SCLC)

Pierwsza linia leczenia pacjentów z drobnokomórkowym rakiem płuca w stadium rozległym (SCLC)

E.1.1.1

Medical condition in easily understood language

Treatment naïve patients with extensive-stage small-cell lung cancer

Nieleczeni wcześniej pacjenci z drobnokomórkowym rakiem płuca w stadium rozległym

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	10041068
E.1.2	Term	Small cell lung cancer extensive stage
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

To evaluate the efficacy of AZD2811 + durvalumab by assessment of the proportion of participants alive and progression free at 12 months APF12 who have not progressed during EP-durvalumab based induction therapy.

Ocena skuteczności stosowania AZD2811 w skojarzeniu z durwalumabem, na podstawie oceny odsetka uczestników pozostających przy życiu i bez progresji choroby w chwili upływu 12 miesięcy (APF12), u których nie stwierdzono progresji podczas leczenia indukcyjnego chemioterapią na bazie etopozydu i platyny (EP) z durwalumabem

E.2.2

Secondary objectives of the trial

- To evaluate efficacy of AZD2811 + durvalumab:
- proportion of participants alive at 12 months OS12, 15 months OS15, and 18 months
OS18 who have not progressed during induction.
- proportion of participants alive and progression free at 6 months APF6 and 9 months
APF9 who have not progressed during induction.
- assessment of Objective response rate (ORR):
- in all participants in induction.
- in participants who had not progressed during induction.
- assessment of PFS in participants who had not progressed during induction.
- assessment of OS in participants who had not progressed during induction.

- To assess the safety and tolerability profile of study intervention in SCLC.

- To evaluate the PK of durvalumab and AZD2811.

- To evaluate the effect of AZD2811 + durvalumab on SCLC symptoms and health-related QoL
using EORTC QLQ-C30 and QLQ-LC13.

Ocena skuteczności stosowania AZD2811 w skojarzeniu z durwalumabem, na podstawie oceny:
1. odsetka uczestników pozostających przy życiu 12 . (OS12), 15 (OS15) i 18 msc.(OS18), bez progresji podczas leczenia indukcyjnego (li)
2. odsetka uczestników pozostających przy życiu i bez progresji choroby 6 (APF6) i 9 msc.(APF9) bez progresji podczas li
3.odsetka odpowiedzi obiektywnych (ORR)
a.u wszystkich pacjentów w fazie li
b.u pacjentów, bez progresji podczas li
4. przeżycia bez progresji choroby (PFS) uczestników bez progresji podczas li
5.całkowitego okresu przeżycia (OS) uczestników bez progresji podczas li
6.Ocena profilu bezpieczeństwa i tolerancji leczenia u pacjentów z drobnokomórkowym rakiem płuca
7.Ocena farmakokinetyki durwalumabu i AZD2811
8.Ocena wpływu AZD2811 + durwalumab na objawy DRP oraz na jakość życia (QoL) uwarunkowaną stanem zdrowia, z użyciem kwestionariuszy EORTC oceny jakości życia (QLQ-C30) i oceny jakości życia u pacjentów z nowotworem płuc (QLQ-LC13).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Documented evidence of extensive stage SCLC (ES-SCLC)
• Participants must be considered suitable to receive a platinum-based chemotherapy regimen, combined with durvalumab, as first-line treatment for ES-SCLC
• No prior exposure to immune-mediated therapy
• Life expectancy ≥12 weeks at Day 1.
• ECOG 0 or 1 at enrolment.

1.Potwierdzone stadium rozległe drobnokomórkowego raka płuc (ES-SCLC)
2.Uczestnicy muszą się kwalifikować do stosowania schematu chemioterapii na bazie platyny w skojarzeniu z durwalumabem jako leczenia pierwszej linii z powodu ES-SCLC
3.Niestosowanie wcześniej leczenia immunologicznego
4.Oczekiwana długość życia ≥12 tygodni
5.Stan sprawności wg skali Światowej Organizacji Zdrowia (WHO)/Eastern Cooperative Oncology Group (ECOG) 0 lub 1 w chwili przydzielania leczenia

E.4

Principal exclusion criteria

• Any history of radiotherapy to the chest prior to systemic therapy or planned consolidation chest radiation therapy
• Has a paraneoplastic syndrome (PNS) of autoimmune systemic steroids or immunosuppressive agents) or has a clinical symptomatology suggesting worsening of PNS
• Active infection including tuberculosis, HIV, hepatitis B and C
• Active or prior documented autoimmune or inflammatory disorders
• Uncontrolled intercurrent illness, including but not limited to interstitial lung disease.

1.Jakakolwiek radioterapia klatki piersiowej w wywiadzie przed rozpoczęciem leczenia ogólnego lub planowana radioterapia konsolidacyjna klatki piersiowej
2.Zespół paraneoplastyczny (PNS) o charakterze autoimmunologicznym, wymagający leczenia ogólnego (podawanych ogólnie kortykosteroidów lub leków immunosupresyjnych) lub objawy kliniczne wskazujące na nasilenie PNS
3.Aktywna faza zakażenia, w tym gruźlica, wirusowe zapalenie wątroby typu B i typu C lub zakażenie ludzkim wirusem upośledzenia odporności (HIV)
4.Udokumentowane aktywne lub wcześniej przebyte choroby autoimmunologiczne lub zapalne
5.Niekontrolowane choroby współistniejące, w tym choroba śródmiąższowa płuc (ILD)

E.5 End points

E.5.1

Primary end point(s)

Maintenance participants alive and progression free (APF12)

Odsetek uczestników pozostających przy życiu i bez progresji choroby w chwili upływu 12 miesięcy (APF12)

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to 12 months

Do 12 miesięcy

E.5.2

Secondary end point(s)

1. Maintenance participants alive at 12 months (OS12), 15 months (OS15), and 18 months (OS18)

2. Maintenance participants alive and progression free at 6 months (APF6) and 9 months (APF9) using investigator assessments according to RECIST 1.1

3. Objective response rate (ORR) for all participants using investigator assessments according to RECIST 1.1.

4. Maintenance participants Progression-free survival (PFS) using investigator assessments according to RECIST 1.1

5. Overall survival (OS) in maintenance participants

6. The safety and tolerability profile of study intervention in SCLC.

7. The pharmacokinetics of durvalumab and AZD2811.

8. Disease-related symptoms & Health-related QoL measured by EORTC QLQ-LC30 & EORTC QLQ-LC13

1.Odsetek uczestników pozostających przy życiu w chwili upływu 12 miesięcy (OS12), 15 miesięcy (OS15) i 18 miesięcy (OS18), w populacji uczestników, którzy przystąpi do fazy leczenia podtrzymującego;
2.Odsetek uczestników pozostających przy życiu i bez progresji choroby w chwili upływu 6 miesięcy (APF6) i 9 miesięcy (APF9) wg. kryteriów RECIST 1.1 ocenionych przez Badacza w populacji uczestników, którzy przystąpią do fazy leczenia podtrzymującego;
3.Odsetek odpowiedzi obiektywnych (ORR) u wszystkich uczestników oceniony przez badacza wg kryteriów RECIST 1.1;
4.Okres przeżycia bez progresji choroby (PFS) oceniony przez badacza wg kryteriów RECIST 1.1, u uczestników, którzy przystąpią do fazy leczenia podtrzymującego
5.Okres przeżycia ogólnego (OS) u uczestników, którzy przystąpią do fazy leczenia podtrzymującego
6.Profil bezpieczeństwa i tolerancji badanej interwencji u pacjentów z drobnokomórkowym rakiem płuca
7.Farmakokinetyka durwalumabu i AZD2811

Objawy DRP oraz jakość życia (QoL), uwarunkowaną stanem zdrowia oceniana za pomocą opracowanego przez Europejską Organizację Badań i Leczenia Raka (EORTC) kwestionariusza oceny jakości życia (QLQ-C30) oraz kwestionariusza oceny jakości życia u pacjentów z nowotworem płuc (QLQ-LC13).

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Up to 18 months

2. Up to 9 months

3. to 8. Up to approximately 3 years

pkt 1 - do 18 miesięcy
pkt 2 – do 9 miesięcy
pkt 3-8-do około 3 lat

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

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

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

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

Korea, Republic of

United States

Poland

Spain

E.8.7

Trial has a data monitoring committee

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 date of the last scheduled procedure for the last treated participant in the study.

Data ostatniej przewidzianej procedury u ostatniego pacjenta uczestniczącego w badaniu.

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

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients with a legally authorised representative (“an individual or judicial or other body authorized under applicable law to consent, on behalf of a prospective subject, to the subject’s participation in the clinical trial”, per ICH GCP E6(R2)).

Pacjenci posiadający prawnie upoważnionego przedstawiciela („osoba fizyczna/ sądowa/inny organ upoważniony na mocy ob. prawa do wyrażenia zgody w imieniu potencjalnego uczestnika na udział uczestnika w badaniu klinicznym”, zgodnie z ICH GCP E6 (R2))

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

100

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 receiving study drug at time of final DCO can continue to receive study drug if investigator feels still of clinical benefit, and will be managed per routine clinical practice. Patients continuing to experience CR, PR, or SD over min. 2 years may be considered for drug discontinuation. Patients who progress during first 52 weeks after the last dose of study drug can be considered for retreatment. The trial must still be active and patient must not meet defined exclusion criteria.

Pacjenci otrzymujący badany lek w dniu odcięcia danych mogą otrzymywać badany lek, jeśli w opinii badacza odnoszą korzyść kliniczną i pozostają pod rutynową opieką. Pacjenci, u których utrzymuje się odpowiedź całkowita, częściowa lub stabilizacja choroby przez min. 2 lata mogą rozważyć odstawienie leku. U pacjentów, z progresją w ciągu pierwszych 52 tyg. po podaniu ostatniej dawki, można rozważyć ponowne leczenie. Badanie musi być aktywne, a pacjent nie może spełniać kryteriów wykluczenia.

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

2021-09-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-06-16

P. End of Trial
P.	End of Trial Status	Completed

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IMP with orphan designation in the indication
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