Clinical trial • Phase I/II • Oncology

SUROVATAMIG (Human IgG4 kappa monoclonal antibody against CD3 and CD19) for Mantle cell lymphoma|Diffuse large B-cell lymphoma|Chronic lymphocytic leukaemia|Small lymphocytic lymphoma

Phase I/II trial of SUROVATAMIG (Human IgG4 kappa monoclonal antibody against CD3 and CD19) for Mantle cell lymphoma|Diffuse large B-cell lymphoma|Chronic…

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Mantle cell lymphoma|Diffuse large B-cell lymphoma|Chronic lymphocytic leukaemia|Small lymphocytic lymphoma
Trial Stage
Phase I/II
Drug Modality
Monoclonal antibody|Small molecule

Key dates

Initial CTIS Submission Date
29-08-2024
First CTIS Authorization Date
07-01-2025

Trial design

open-label, comparators listed in protocol: prednisone (prednisone/prednisolone), rituximab, doxorubicin (doxorubicin hydrochloride), vincristine, acalabrutinib (calquence), cyclophosphamide. dose and schedule not specified in the ctis metadata.-controlled, adaptive Phase I/II trial across 21 sites in Spain, Czechia, France and others.

Open Label
Yes
Comparator
Comparators listed in protocol: PREDNISONE (Prednisone/Prednisolone), RITUXIMAB, DOXORUBICIN (doxorubicin hydrochloride), VINCRISTINE, ACALABRUTINIB (Calquence), CYCLOPHOSPHAMIDE. Dose and schedule not specified in the CTIS metadata.
Adaptive
True, Dose-escalation to determine RP2D informed by DLT assessments and safety (RP2D determination is a stated main objective). Specific escalation rules or stopping rules not provided in the CTIS metadata.
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
246

Eligibility

Recruits 246 Vulnerable population selected. Country-specific informed consent documents include specific forms for pregnant partners and other vulnerable-related procedures (documents titled 'Other Pregnant Partner ICF' and country ICF addenda). Consent is obtained via subject information and informed consent forms; participants are adults (Age ≥ 18). No assent procedures for minors are described..

Vulnerable Population
Vulnerable population selected. Country-specific informed consent documents include specific forms for pregnant partners and other vulnerable-related procedures (documents titled 'Other Pregnant Partner ICF' and country ICF addenda). Consent is obtained via subject information and informed consent forms; participants are adults (Age ≥ 18). No assent procedures for minors are described.

Inclusion criteria

  • {"criterion_text":"- All sub- studies: Age ≥ 18 years\n- Sub-study 1, Cohort 1A and Cohort 1C: at least 2 prior lines of systemic therapy for CLL/SLL\n- Sub-study 1, Cohort 1B: at least 1 prior line of therapy and BTKi sensitive or naïve\n- Sub-study 2: MCL diagnosis per WHO\n- Sub-study 3: Absolute lymphocytes count of < 5 × 109 cells/L\n- Sub-study 3: Haemoglobin ≥ 9 g/dL\n- Sub-study 2: Clinical Stage II, III, or IV per Ann Arbor classification\n- Sub-study 2: At least 1 measurable site per Lugano\n- Sub-study 2: ALC < 10,000\n- Sub- study 2, Cohort 2A and Cohort 2C: Relapsed or Progressed after 2 or more prior systemic therapy for MCL including BTKi\n- Sub-study 3: Large B-cell lymphoma per WHO 2022 or R/R B-NHL after at least 1 prior line of therapy\n- Sub-study 3: LVEF >50%\n- Sub-study 3: IPI 2-5 for participants with untreated LBCL diagnoses\n- Sub-study 3: At least 1 measurable site as per Lugano\n- Sub-study 1: Contraception during treatment and until at least x days after the last dose of AZD0486 and until 2 days after the last dose of acalabrutinib, whichever is longer.\n- All sub- studies: ECOG performance status 0 to 2\n- Sub-study 3: Contraception until x days after the last dose of AZD0486, 4 months after the last dose of vincristine, and 6 months after the last dose of cyclophosphamide or doxorubicin, (or as required by local prescribing information) whichever is longer.\n- All sub-studies: Contraception during treatment and at least x days after final dose\n- All sub- studies: Confirmed CD19 expression if prior anti-CD19 therapy\n- Sub-study 1: CLL/SLL diagnosis and meets iwCLL criteria for treatment\n- Sub-study 1: SLL: at least 1 measurable site per Lugano\n- Sub-study 1: Absolute lymphocytes <10,000"}

Exclusion criteria

  • {"criterion_text":"- All sub- studies: CNS lymphoma\n- All sub-studies: Radiation therapy within 28 days of Cycle 1 Day 1\n- All sub-studies: Prior CAR-T therapy or auto-HSCT within 12 weeks or prior TCE within 8 weeks of Cycle 1 Day 1\n- All sub- studies: Prior Grade ≥ 3 CRS or ICANS event\n- Sub-study 1: CLL transformation to more aggressive lymphoma\n- All sub- studies: Active, significant, or uncontrolled infection or autoimmune disease requiring systemic therapy which places participant at unacceptable risk if he/she were to participate in the study\n- Sub-study 1, Cohort 1B: bleeding diathesis, treatment with strong CYP3A inhibitor or inducer, history of ICH or stroke within 24 weeks, GI malabsorption, receiving vitamin K antagonist\n- Sub-study 2 Exclusion Criteria Refer to Section 5.2 of the Master Protocol.\n- Sub-study 3: Mediastinal grey-zone lymphoma, Burkitt, Richter’s transformation, primary effusion LBCL\n- Sub-study 3: Cumulative dose of anthracycline ≥ 150 mg/m2\n- All sub- studies: Major Surgical procedure within 14 days before the first dose of study drug\n- All sub- studies: Clinically significant CV disease\n- All sub- studies: Unresolved non-haematological Grade ≥ 2 AEs (NCI CTCAE V5.0) from prior anticancer therapy (except alopecia or fatigue)\n- All sub-studies: Any anticancer systemic therapy within 5 half-lives or 21 days (whichever is shorter) prior to Cycle 1 Day 1"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Incidence, nature and severity of AEs/SAEs based on NCI CTCAE v5.0/ASTCT criteria; changes in laboratory data, and vital signs compared with baseline","definition_or_measurement_approach":"Measured by NCI CTCAE v5.0 and ASTCT criteria; laboratory data and vital signs compared with baseline"}
  • {"endpoint_text":"- Incidence of Dose Limiting Toxicity (DLTs)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Incidence and severity of AESIs","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Incidence and nature of study drug discontinuation, dose reduction and dose delay due to AEs","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
246
Recruitment Window Months
36
Consent Approach
Informed consent is obtained using country-specific subject information and informed consent forms (multiple 'Country ICF' documents listed for Spain, Czechia, France, Germany, Denmark). Participants are adults (Age ≥ 18) and provide their own consent. Additional specific consent forms are provided for pregnant partners and optional procedures/genetic research. Consent materials are provided in local languages as evidenced by ICF document titles (e.g., Spanish, French, Czech, German, Danish, English). No assent process for minors is described.

Geography

Total Number Of Sites
21
Total Number Of Participants
200

Spain

Earliest CTIS Part Ii Submission Date
04-12-2024
Latest Decision Or Authorization Date
14-10-2025
Processing Time Days
314
Number Of Sites
6
Number Of Participants
52

Sites

Site Name
University Hospital Son Espases
Department Name
7002: Hematologia
Principal Investigator Name
Antonio Manuel Gutierrez Garcia
Principal Investigator Email
antoniom.gutierrez@ssib.es
Contact Person Name
Antonio Manuel Gutierrez Garcia
Contact Person Email
antoniom.gutierrez@ssib.es
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
7006: Hematología
Principal Investigator Name
Javier López Jiménez
Principal Investigator Email
jljimenez@salud.madrid.org
Contact Person Name
Javier López Jiménez
Contact Person Email
jljimenez@salud.madrid.org
Site Name
Hospital Universitario Fundacion Jimenez Diaz
Department Name
7001: Hematología y Hemoterapia
Principal Investigator Name
Daniel Morillo Giles
Principal Investigator Email
dmorillo@startmadrid.com
Contact Person Name
Daniel Morillo Giles
Contact Person Email
dmorillo@startmadrid.com
Site Name
Hospital Clinic De Barcelona
Department Name
7004: Hematología
Principal Investigator Name
Eva Giné Soca
Principal Investigator Email
EGINE@clinic.ub.es
Contact Person Name
Eva Giné Soca
Contact Person Email
EGINE@clinic.ub.es
Site Name
Complexo Hospitalario Universitario De Santiago
Department Name
7003: Hematología
Principal Investigator Name
Adrián Mosquera Orgueira
Principal Investigator Email
Adrian.Mosquera.Orgeira@sergas.es
Contact Person Name
Adrián Mosquera Orgueira
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
7005: Hematología
Principal Investigator Name
Rafael Andreu Lapiedra
Principal Investigator Email
andreu_raflap@gva.es
Contact Person Name
Rafael Andreu Lapiedra
Contact Person Email
andreu_raflap@gva.es

Czechia

Earliest CTIS Part Ii Submission Date
04-12-2024
Latest Decision Or Authorization Date
14-10-2025
Processing Time Days
314
Number Of Sites
3
Number Of Participants
32

Sites

Site Name
Institute Of Hematology And Blood Transfusion
Department Name
1903:Oddělení buněčné terapie
Principal Investigator Name
Robert Pytlik
Principal Investigator Email
Robert.Pytlik@uhkt.cz
Contact Person Name
Robert Pytlik
Contact Person Email
Robert.Pytlik@uhkt.cz
Site Name
Fakultni Nemocnice Ostrava
Department Name
1901:Klinika plicnich nemoci a TBC
Principal Investigator Name
Roman Hajek
Principal Investigator Email
roman.hajek@fno.cz
Contact Person Name
Roman Hajek
Contact Person Email
roman.hajek@fno.cz
Site Name
Vseobecna Fakultni Nemocnice V Praze
Department Name
1902:I. Interni klinika - klinika hematologie VFN a 1. LF UK v Praze
Principal Investigator Name
Marek Trneny
Principal Investigator Email
trneny@cesnet.cz
Contact Person Name
Marek Trneny
Contact Person Email
trneny@cesnet.cz

France

Earliest CTIS Part Ii Submission Date
11-10-2024
Latest Decision Or Authorization Date
09-10-2025
Processing Time Days
363
Number Of Sites
4
Number Of Participants
36

Sites

Site Name
Hopital Saint Louis
Department Name
2303: Service d’Hémato-oncologie
Principal Investigator Name
Catherine Thieblemont
Principal Investigator Email
catherine.thieblemont@aphp.fr
Contact Person Name
Catherine Thieblemont
Contact Person Email
catherine.thieblemont@aphp.fr
Site Name
Institut Curie
Department Name
2302: Oncology
Principal Investigator Name
Clementine Sarkozy
Principal Investigator Email
clementine.sarkozy@curie.fr
Contact Person Name
Clementine Sarkozy
Contact Person Email
clementine.sarkozy@curie.fr
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
2301: Hématologie clinique
Principal Investigator Name
Guillaume CARTRON
Principal Investigator Email
g-cartron@chu-montpellier.fr
Contact Person Name
Guillaume CARTRON
Contact Person Email
g-cartron@chu-montpellier.fr
Site Name
Institut Gustave Roussy
Department Name
2304: Département d’Innovations Thérapeutiques et d’essais Précoces (DITEP)
Principal Investigator Name
Vincent Ribrag
Principal Investigator Email
vincent.ribrag@gustaveroussy.fr
Contact Person Name
Vincent Ribrag

Germany

Earliest CTIS Part Ii Submission Date
04-12-2024
Latest Decision Or Authorization Date
13-10-2025
Processing Time Days
313
Number Of Sites
4
Number Of Participants
42

Sites

Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
2602:Hemat/Transfusion Med
Principal Investigator Name
Martin Dreyling
Principal Investigator Email
Martin.Dreyling@med.uni-muenchen.de
Contact Person Name
Martin Dreyling
Site Name
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Department Name
2604: Schwerpunkt Endokrinologie
Principal Investigator Name
Georg Hess
Principal Investigator Email
georg.hess@unimedizin-mainz.de
Contact Person Name
Georg Hess
Contact Person Email
georg.hess@unimedizin-mainz.de
Site Name
Universitaetsklinikum Schleswig-Holstein AöR
Department Name
2603:Medizinische Klinik II
Principal Investigator Name
Christiane Pott
Principal Investigator Email
c.pott@med2.uni-kiel.de
Contact Person Name
Christiane Pott
Contact Person Email
c.pott@med2.uni-kiel.de
Site Name
Universitaetsklinikum Wuerzburg AöR
Department Name
2601:Med. Klinik und Poliklinik II
Principal Investigator Name
Max Topp
Principal Investigator Email
topp_m@ukw.de
Contact Person Name
Max Topp
Contact Person Email
topp_m@ukw.de

Denmark

Earliest CTIS Part Ii Submission Date
16-12-2024
Latest Decision Or Authorization Date
25-11-2025
Processing Time Days
344
Number Of Sites
4
Number Of Participants
38

Sites

Site Name
Rigshospitalet
Department Name
2002:Department of Haematology and Phase 1 Unit.
Principal Investigator Name
Martin Hutchings
Principal Investigator Email
Martin.hutchings@regionh.dk
Contact Person Name
Martin Hutchings
Contact Person Email
Martin.hutchings@regionh.dk
Site Name
Aalborg University Hospital
Department Name
2003:Department of Haematology
Principal Investigator Name
Thor Høyer
Principal Investigator Email
thhc@rn.dk
Contact Person Name
Thor Høyer
Contact Person Email
thhc@rn.dk
Site Name
Region Midtjylland
Department Name
2001:Department of Haematology
Principal Investigator Name
Hans Bentzen
Principal Investigator Email
hansbent@rm.dk
Contact Person Name
Hans Bentzen
Contact Person Email
hansbent@rm.dk
Site Name
Odense University Hospital
Department Name
2004: Oncology
Principal Investigator Name
Jacob Haaber Christensen
Principal Investigator Email
jacob.h.christensen@rsyd.dk
Contact Person Name
Jacob Haaber Christensen
Contact Person Email
jacob.h.christensen@rsyd.dk

Sponsor

Primary sponsor

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

Contract research organisations

Name
Parexel International (IRL) Limited
Responsibilities
Sponsor duties codes: 1,10,11,12,14,2,5,6,7,8,9; contact Clinicaltrial.Enquiries@parexel.com

Third parties

  • {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"1,10,11,12,14,2,5,6,7,8,9","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
AZD0486
Active Substance
SUROVATAMIG (Human IgG4 kappa monoclonal antibody against CD3 and CD19)
Modality
Monoclonal antibody
Routes Of Administration
Intravenous; Subcutaneous
Authorisation Status
Not authorised (prodAuthStatus:1)
Combination Treatment
Yes

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