Clinical trial • Phase I/II • Oncology|Haematology

AZD5492 for B-cell malignancies|Diffuse large B-cell lymphoma|Follicular lymphoma|Mantle cell lymphoma|Chronic lymphocytic leukemia|Small lymphocytic lymphoma|Relapsed or refractory B-cell malignancies

Phase I/II trial of AZD5492 for B-cell malignancies|Diffuse large B-cell lymphoma|Follicular lymphoma|Mantle cell lymphoma|Chronic lymphocytic leukemia|Sm…

Overview

Trial Therapeutic Area
Oncology|Haematology
Trial Disease
B-cell malignancies|Diffuse large B-cell lymphoma|Follicular lymphoma|Mantle cell lymphoma|Chronic lymphocytic leukemia|Small lymphocytic lymphoma|Relapsed or refractory B-cell malignancies
Trial Stage
Phase I/II
Drug Modality
Bispecific antibody

Key dates

Initial CTIS Submission Date
09-07-2024
First CTIS Authorization Date
25-10-2024

Trial design

open-label, adaptive Phase I/II trial in Spain, Denmark, Italy and others.

Open Label
Yes
Adaptive
True, Module 1 includes a Phase I dose escalation (Part A) to determine safety/tolerability/preliminary efficacy and dose(s)/schedule(s) for Part B; Part B is a dose optimization/expansion to characterize safety, antitumor activity and determine RP2D and may be initiated upon protocol amendment if data from Part A support further evaluation.
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
110

Eligibility

Recruits 110 Vulnerable population selected (isVulnerablePopulationSelected: true). Subject information and informed consent form documents are listed for adult subjects, pregnant partners, newborns and optional genomics research, but detailed consent/assent handling text is not provided in the available data..

Vulnerable Population
Vulnerable population selected (isVulnerablePopulationSelected: true). Subject information and informed consent form documents are listed for adult subjects, pregnant partners, newborns and optional genomics research, but detailed consent/assent handling text is not provided in the available data.

Inclusion criteria

  • {"criterion_text":"- ≥18 years of age\n- The above is a summary, other inclusion criteria details may apply\n- Histologically documented CD20+ mature B-cell neoplasm\n- Large B-cell lymphoma\n- Follicular lymphoma\n- Mantle cell lymphoma\n- Chronic lymphocytic leukemia\n- Small lymphocytic lymphoma\n- Relapsed, progressive and/or refractory disease following at least 2 prior lines of therapy\n- ECOG performance status of = 2 (Note: in EU countries this inclusion is ECOG performance status of < 2)."}

Exclusion criteria

  • {"criterion_text":"- Any neoplasm histology not specified in the IC section\n- Active CNS involvement in lymphoma or CNS pathology.\n- CNS pathology including but not limited to any history of seizure disorder/epilepsy\n- Prior allogeneic HSCT within 180 days, prior autologous HSCR within 90 days, or cell therapy within 90 days of start of therapy.\n- History of Grade ≥ 3 CRS or Grade ≥ 3 ICANS.\n- Active and uncontrolled infections.\n- Unresolved AEs ≥2 Grade, from prior therapies.\n- The above is a summary, other exclusion criteria details may apply."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Occurrence of Dose-Limiting Toxicities (DLTs)\n- Incidence and severity of AEs, AESIs, and SAEs\n- SAEs/AEs leading to discontinuation of AZD5492\n- Clinically significant alterations in vital signs and abnormal laboratory parameters","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Evaluate the preliminary antitumor activity of AZD5492 in participants with R/R B-cell malignancies, by looking at: - ORR (Overall Response Rate), CR Rate, DoR (duration of response), and PFS (progression free survival) according to Lugano criteria and iwCLL 2018 criteria; - OS (overall survival).","definition_or_measurement_approach":"Assess antitumor activity using ORR, CR rate, DoR, PFS according to Lugano criteria and iwCLL 2018 criteria; OS (overall survival)."}
  • {"endpoint_text":"- Characterize pharmacokinetics profile of AZD5492, by: - Determining PK parameters, including but not limited to Cmax (maximum observed concentration), AUC (Area under the curve), clearance and t½ (half-life). - Antibody serum concentration.","definition_or_measurement_approach":"Determine PK parameters including Cmax, AUC, clearance, t½ and measure antibody serum concentrations."}
  • {"endpoint_text":"- Determine the immunogenicity of AZD5492: the number and percentage of participants who develop ADA (Anti Drug Antibodies).","definition_or_measurement_approach":"Report number and percentage of participants who develop anti-drug antibodies (ADA)."}

Recruitment

Planned Sample Size
110
Recruitment Window Months
41
Consent Approach
Informed consent is obtained from adult participants. Subject information and informed consent form (SIS and ICF) documents are provided for adult subjects, pregnant partners, newborns, and optional genomics research; multiple ICF/synopsis documents and language-specific protocol synopses are present (titles indicate translations/lay language in Spanish, French, Italian, German). No detailed text about assent for minors or age-specific consent processes is provided in the available data.

Geography

Total Number Of Sites
12
Total Number Of Participants
66

Spain

Earliest CTIS Part Ii Submission Date
01-10-2024
Latest Decision Or Authorization Date
22-12-2025
Processing Time Days
447
Number Of Sites
3
Number Of Participants
20

Sites

Site Name
Hospital Universitario Fundacion Jimenez Diaz
Department Name
Hematology
Principal Investigator Name
Raúl Córdoba Mascuñano
Principal Investigator Email
raul.cordoba@fjd.es
Contact Person Name
Raúl Córdoba Mascuñano
Contact Person Email
raul.cordoba@fjd.es
Site Name
Hospital Universitari Vall D Hebron
Department Name
Hematology
Principal Investigator Name
Pau Abrisqueta Costa
Principal Investigator Email
pabrisqueta@vhio.net
Contact Person Name
Pau Abrisqueta Costa
Contact Person Email
pabrisqueta@vhio.net
Site Name
Institut Catala D'oncologia
Department Name
Hematology
Principal Investigator Name
Ana María Sureda Balari
Principal Investigator Email
asureda@iconcologia.net
Contact Person Name
Ana María Sureda Balari
Contact Person Email
asureda@iconcologia.net

Denmark

Earliest CTIS Part Ii Submission Date
11-10-2024
Latest Decision Or Authorization Date
18-12-2025
Processing Time Days
433
Number Of Sites
1
Number Of Participants
10

Sites

Site Name
Rigshospitalet
Department Name
Department of Hematology
Principal Investigator Name
Martin Hutchings
Principal Investigator Email
martin.hutchings@regionh.dk
Contact Person Name
Martin Hutchings
Contact Person Email
martin.hutchings@regionh.dk

Italy

Earliest CTIS Part Ii Submission Date
25-09-2024
Latest Decision Or Authorization Date
19-01-2026
Processing Time Days
481
Number Of Sites
2
Number Of Participants
12

Sites

Site Name
Ospedale San Raffaele S.r.l.
Department Name
Oncologia Medica
Principal Investigator Name
Paolo Prospero Ghia
Principal Investigator Email
ghia.paolo@hsr.it
Contact Person Name
Paolo Prospero Ghia
Contact Person Email
ghia.paolo@hsr.it
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
Malattie oncologiche ed ematologiche
Principal Investigator Name
Pier Luigi Zinzani
Principal Investigator Email
pierluigi.zinzani@unibo.it
Contact Person Name
Pier Luigi Zinzani
Contact Person Email
pierluigi.zinzani@unibo.it

France

Earliest CTIS Part Ii Submission Date
14-10-2024
Latest Decision Or Authorization Date
23-12-2025
Processing Time Days
435
Number Of Sites
2
Number Of Participants
12

Sites

Site Name
Institut Gustave Roussy
Department Name
Hematology
Principal Investigator Name
Vincent Ribrag
Principal Investigator Email
vincent.ribrag@gustaveroussy.fr
Contact Person Name
Vincent Ribrag
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Clinical hematology and cell therapy
Principal Investigator Name
François-Xavier Gros
Principal Investigator Email
francois-xavier.gros@chu-bordeaux.fr
Contact Person Name
François-Xavier Gros

Germany

Earliest CTIS Part Ii Submission Date
18-10-2024
Latest Decision Or Authorization Date
13-05-2026
Processing Time Days
572
Number Of Sites
4
Number Of Participants
12

Sites

Site Name
Universitaetsmedizin Goettingen
Department Name
Klinik für Haematologie und Medizinische Onkologie
Principal Investigator Name
Johannes Jung
Principal Investigator Email
johannes.jung@med.uni-goettingen.de
Contact Person Name
Johannes Jung
Site Name
Klinikum rechts der Isar der TU Muenchen AöR
Department Name
Klinik und Poliklinik für Innere Medizin III
Principal Investigator Name
Maike Hefter
Principal Investigator Email
maike.hefter@mri.tum.de
Contact Person Name
Maike Hefter
Contact Person Email
maike.hefter@mri.tum.de
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Comprehensive Cancer Center Ulm – Early Clinical Trials Unit
Principal Investigator Name
Andreas Viardot
Principal Investigator Email
andreas.viardot@uniklinik-ulm.de
Contact Person Name
Andreas Viardot
Site Name
Universitaetsklinikum Wuerzburg AöR
Department Name
"Medizinische Klinik und Poliklinik II, Zentrum für Innere Medizin"
Principal Investigator Name
Max Topp
Principal Investigator Email
topp_m@ukw.de
Contact Person Name
Max Topp
Contact Person Email
topp_m@ukw.de

Sponsor

Primary sponsor

Full Name
AstraZeneca AB
Organisation Type
Pharmaceutical company
Country Of Registered Address
Sweden

Investigational products

Investigational Product Name
AZD5492
Active Substance
AZD5492
Modality
Bispecific antibody
Routes Of Administration
Subcutaneous
Route
Subcutaneous
Combination Treatment
Yes

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