Clinical Trials Register

Summary
EudraCT Number:	2021-003569-36
Sponsor's Protocol Code Number:	D9571C00001
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:	2022-01-19
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

2021-003569-36

A.3

Full title of the trial

A Phase I/II Open-label, Multi-center Study to Assess Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AZD7789, an Anti-PD-1 and Anti-TIM-3 Bispecific Antibody, in Patients with Relapsed or Refractory
Classical Hodgkin Lymphoma

Uno studio, in aperto, multicentrico, di fase I/II che valuta la sicurezza, la tollerabilità, la farmacocinetica e l’efficacia preliminare di AZD7789, un anticorpo bispecifico anti-PD-1 e anti-TIM-3, in pazienti con linfoma classico di Hodgkin recidivante o refrattario

A.3.1

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

Open-label, Multi-center Study to Assess the Safety and Preliminary Efficacy of AZD7789 in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma (cHL)

Studio multicentrico in aperto per valutare la sicurezza e l’efficacia preliminare di AZD7789 in pazienti con linfoma di Hodgkin classico (cHL) recidivante o refrattario

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

D9571C00001

A.5.4

Other Identifiers

Name:

IND

Number:

157025

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	1800 Concord Pike
B.5.3.2	Town/ city	Wilmington, DE
B.5.3.3	Post code	19803
B.5.3.4	Country	United States
B.5.4	Telephone number	000000
B.5.5	Fax number	000000
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	AZD7789
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Powder 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	NA
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	AZD7789
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

Relapse/Refractory Classical Hodgkin Lymphoma

Linfoma di Hodgkin classico recidivante/refrattario

E.1.1.1

Medical condition in easily understood language

Cancer of the lymphatic system

Carcinoma del sistema linfatico

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10080208
E.1.2	Term	Classical Hodgkin lymphoma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part A Dose Escalation:
• To assess the safety and tolerability of AZD7789 in participants with r/r cHL
• To establish the maximum tolerated dose, or optimal biological dose, and recommended Phase 2 dose

Part B Dose Expansion (all):
• To assess the safety and tolerability of AZD7789 in participants with r/r cHL

Part B Dose Expansion (B1):
• To assess the preliminary antitumor activity of AZD7789 in participants with r/r cHL (anti-PD-1/PD-L1 exposed)

Part B Dose Expansion (B2):
• To assess the preliminary antitumor activity of AZD7789 in patients with r/r cHL (anti PD-1/PD-L1 naïve)

Parte A, incremento della dose
•Valutare la sicurezza e la tollerabilità di AZD7789 in partecipanti con cHL r/r
•Stabilire la dose massima tollerata o la dose biologica ottimale e la dose raccomandata per la fase 2

Parte B, espansione della dose (tutti)
•Valutare la sicurezza e la tollerabilità di AZD7789 in partecipanti con cHL r/r

Parte B, espansione della dose (B1)
•Valutare l’attività antitumorale preliminare di AZD7789 in partecipanti con cHL r/r (esposti a terapia anti-PD-1/PD-L1)

Parte B, espansione della dose (B2)
•Valutare l’attività antitumorale preliminare di AZD7789 in partecipanti con cHL r/r (naïve alla terapia anti-PD-1/PD-L1)

E.2.2

Secondary objectives of the trial

Part A Dose Escalation:
• To assess the preliminary antitumor activity of AZD7789 in participants with r/r cHL

Part B Dose Expansion:
• To further assess the preliminary antitumor activity of AZD7789 in participants with r/r cHL

Part A Dose Escalation and Part B Dose Expansion:
• To assess the PK of AZD7789 in participants with r/r cHL
• To assess the immunogenicity of AZD7789 in participants with r/r cHL

Parte A, incremento della dose
•Valutare l’attività antitumorale preliminare di AZD7789 in partecipanti con cHL r/r

Parte B, espansione della dose
•Valutare ulteriormente l’attività antitumorale preliminare di AZD7789 in partecipanti con cHL r/r

Parte A, incremento della dose e Parte B, espansione della dose
•Valutare la PK di AZD7789 in partecipanti con cHL r/r
•Valutare l’immunogenicità di AZD7789 in partecipanti con cHL r/r

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Other types of substudies
Specify title, date and version of each substudy with relative objectives: Optional Genomics Initiative Sample
A saliva sample for DNA isolation will be collected from patients who have consented to participate in the genetic analysis component of the study. Participation is optional. Patients who do not wish to participate
in the genetic research may still participate in the study.

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Optional Genomics Initiative Sample
Un campione di saliva per isolare il DNA verrà prelevato dai paziento che hanno acconsentito di partecipare alla componente di analisi genetica dello studio. La partecipazione è opzionale. I pazienti che non desiderano partecipare alla ricerca genetica possono continuare a partecipare allo studio.

E.3

Principal inclusion criteria

1. Must be >= 18 years of age at the time of obtaining informed consent
2. Eastern Cooperative Oncology Group performance status of 0 or 1 at screening
3. Must have at least one PET-avid measurable lesion according to Modified Lugano Criteria
4. Confirmed histological diagnosis of active relapse/refractory cHL
5. Must have failed at least 2 prior lines of systemic therapy. In part A dose escalation and part B dose expansion cohort B1, the prior lines of therapy must include at least 3 cycles of an anti-PD-1/PD-L1 therapy. In part B dose expansion cohort B2, prior anti-PD-1/PD-L1 therapy is excluded. For all participants, no previous treatment with anti-TIM-3 is allowed. Previous anti-CTLA-4 treatment is acceptable with at least 2 months washout period prior to study entry
6. Adequate organ and bone marrow function measured within 7 days prior to first dose
7. Non-pregnant women and willingness of female participants to avoid pregnancy or male participants willing to avoid fathering children through highly effective methods of contraception

1.Devono avere >=18 anni di età al momento del ricevimento del consenso informato
2.Stato della prestazione pari a 0 o 1 allo screening secondo l’Eastern Cooperative Oncology Group (ECOG).
3.Devono presentare almeno una lesione misurabile avida alla PET secondo i criteri di Lugano modificati
4.Diagnosi istologica confermata di linfoma di Hodgkin classico (cHL) recidivante/refrattario attivo
5.Devono avere mostrato insuccesso in almeno 2 precedenti linee di terapia sistemica. Nella parte A di incremento della dose e nella parte B della coorte di espansione della dose B1, le linee precedenti di terapia devono includere almeno 3 cicli di una terapia anti-PD-1/PD-L1. Nella parte B della coorte di espansione della dose B2 è esclusa la precedente terapia anti-PD-1/PD-L1. Per tutti i partecipanti, non è consentito alcun trattamento precedente con anti-TIM-3. Il precedente trattamento anti-CTLA-4 è accettabile con un periodo di washout di almeno 2 mesi prima dell’ingresso nello studio
6.Adeguata funzionalità d’organo e del midollo osseo misurata nei 7 giorni precedenti la prima dose
7.Donne non in gravidanza e volontà delle partecipanti di sesso femminile di evitare la gravidanza o partecipanti di sesso maschile disposti a evitare di procreare con metodi contraccettivi altamente efficaci

E.4

Principal exclusion criteria

1. Unresolved toxicities of >= Grade 2 from prior therapy
2. Any prior >= Grade 3 imAE while receiving immunotherapy
3. Participants with CNS involvement or leptomeningeal disease.
4. History of organ transplantation (e.g., stem cell or solid organ transplant).
5. Any venous or arterial thromboembolic event within <= 6 months prior to the first dose of study intervention.
6. Infectious disease exclusions: Active infection including TB, HIV, hepatitis A, chronic or active hepatitis B, chronic or active hepatitis C, active COVID-19 infection
7. History of arrhythmia which is requires treatment; symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia
8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiomyopathy of any etiology, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled diabetes mellitus, unstable angina pectoris, history of myocardial infarction within the past 6 months, serious chronic gastrointestinal conditions associated with diarrhea, active noninfectious skin disease
9. Active or prior documented autoimmune or inflammatory disorders, including inflammatory bowel disease (eg, colitis or Crohn's disease), diverticulitis (with the exception of diverticulosis), systemic
lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.. Some exceptions have been
specified in the protocol
10. Past medical history of interstitial lung disease (ILD), druginduced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD

1.Tossicità non risolte di grado >= 2 dalla terapia precedente
2.Qualsiasi precedente evento avverso immuno-mediato (imAE) di grado >= 3 durante la somministrazione dell’immunoterapia
3.Partecipanti con coinvolgimento del SNC o malattia leptomeningea.
4.Anamnesi di trapianto d’organo (per es., trapianto di cellule staminali o di organo solido).
5.Qualsiasi evento tromboembolico venoso o arterioso nei <= 6 mesi precedenti la prima dose di trattamento dello studio.
6.Esclusioni di malattie infettive: infezione attiva tra cui tubercolosi (TB), HIV, epatite A, epatite B cronica o attiva, epatite C cronica o attiva, infezione attiva da COVID-19
7.Anamnesi di aritmia che richiede trattamento; fibrillazione atriale sintomatica o non controllata nonostante il trattamento o tachicardia ventricolare sostenuta asintomatica
8.Malattia intercorrente non controllata tra cui, a titolo esemplificativo ma non esaustivo, infezione attiva o in corso, cardiomiopatia di qualsiasi eziologia, insufficienza cardiaca congestizia sintomatica, ipertensione non controllata, diabete mellito non controllato, angina pectoris instabile, anamnesi di infarto miocardico negli ultimi 6 mesi, serie condizioni gastrointestinali croniche associate a diarrea, malattia cutanea non infettiva attiva
9.Disturbi autoimmuni o infiammatori attivi o pregressi documentati, tra cui malattia infiammatoria intestinale (per es., colite o malattia di Crohn), diverticolite (a eccezione della diverticolosi), lupus eritematoso sistemico, sindrome da sarcoidosi o sindrome di Wegener (granulomatosi associata a poliangioite), malattia di Graves, artrite reumatoide, ipofisite, uveite, ecc. Alcune eccezioni sono state specificate nel protocollo
10.Anamnesi medica pregressa di malattia polmonare interstiziale (ILD), ILD indotta da farmaci, polmonite da radiazioni che richiede un trattamento steroideo o qualsiasi evidenza di ILD clinicamente attiva

E.5 End points

E.5.1

Primary end point(s)

Part A Dose Escalation:
• Incidence of AEs, imAEs, and SAEs
• Incidence of AEs leading to discontinuation of AZD7789
• Changes from baseline and clinically significant alterations in vital signs, laboratory parameters, and ECG results
• Incidence of dose-limiting toxicities
Part B Dose Expansion (all):
• Incidence of AEs, imAEs, and SAEs
• Incidence of AEs leading to discontinuation of AZD7789
• Changes from baseline and clinically significant alterations in vital signs, laboratory parameters, and ECG results
Part B Dose Expansion (B1):
• Objective Response Rate (defined as the proportion of patients with complete remission or partial remission)
Part B Dose Expansion (B2):
• Complete Response Rate (defined as the proportion of patients with complete remission)

Parte A Incremento della dose:
•Incidenza di AE, imAE e SAE
•Incidenza di AE che porta a interruzione di AZD7789
•Variazioni rispetto al basale e alterazioni clinicamente significative nei segni vitali, nei parametri di laboratorio e nei risultati ECG
•Incidenza di tossicità dose-limitanti
Parte B espansione della dose (tutti)
•Incidenza di AE, imAE e SAE
•Incidenza di AE che porta a interruzione di AZD7789
•Variazioni rispetto al basale e alterazioni clinicamente significative nei segni vitali, nei parametri di laboratorio e nei risultati ECG
Parte B Espansione della dose (B1):
•Tasso di risposta obiettiva (definito come la percentuale di pazienti con remissione completa o remissione parziale)
Parte B Espansione della dose (B2):
•Tasso di risposta completa (definito come la percentuale di pazienti con remissione completa)

E.5.1.1

Timepoint(s) of evaluation of this end point

Throughout the study design at various timepoints.

Durante tutto lo studio in corrispondenza di vari endpoints

E.5.2

Secondary end point(s)

Part A Dose Escalation:
• Complete Response Rate, Objective Response Rate, DoR, and DoCR
• PFS including landmarks at 12 and 24 months
• OS including landmarks at 12 and 24 months

Part B Dose Expansion:
• DoR and DoCR
• PFS b including landmarks at 12 and 24 months
• OS including landmarks at 12 and 24 months

Part A Dose Escalation and Part B Dose Expansion
• PK parameters including the maximum observed concentration, area
under the concentration-time curve, clearance and terminal elimination
half life
• Incidence of anti-drug antibodies against AZD7789 in serum.

Parte A, incremento della dose
•Tasso di risposta completa, Tasso di risposta obiettiva, Durata Della Risposta (DoR) e Durata della Risposta Completa (DoCR)
•Sopravvivenza Libera da Progressione (PFS)a, inclusi i punti di interesse a 12 e 24 mesi
•Sopravvivenza Complessiva (OS), inclusi i punti di interesse a 12 e 24 mesi

Parte B, espansione della dose
•DoR e DoCR
•PFSb, inclusi i punti di interesse a 12 e 24 mesi
•OS, inclusi i punti di interesse a 12 e 24 mesi

Parte A, incremento della dose e Parte B, espansione della dose
•Parametri PK, comprese la concentrazione massima osservata, l’area sotto la curva concentrazione-tempo, la clearance e l’emivita di eliminazione terminale
•Incidenza di anticorpi anti-farmaco diretti contro AZD7789 nel siero

E.5.2.1

Timepoint(s) of evaluation of this end point

Throughout the study design at various timepoints.

Durante tutto lo studio in corrispondenza di vari endpoints

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Phase I/II open label multi center, dose escalation and dose expansion study.

Studio in aperto di fase I/II multi center,

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Phase I/II open label multi center, dose escalation and dose expansion study.

Studio di fase I/II in aperto multicentrico, di aumento e espansione della dose

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

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

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

Australia

Canada

Denmark

France

Germany

Italy

Portugal

Spain

United Kingdom

United States

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 end of the study is defined as the date of the last visit of the last participant in the study or last scheduled procedure for the last participant in the study globally.

La fine dello studio è definita come la data dell'ultima visita dell'ultimo partecipante allo studio o l'ultima procedura schedulata per l'ultimo partecipante nello studio a livello globale

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:

144

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

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

180

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)

None

Nessuno

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

2022-05-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-02-10

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

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IMP with orphan designation in the indication
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