Clinical trial • Phase I/II • Oncology

AZD0305 for Multiple myeloma

Phase I/II trial of AZD0305 for Multiple myeloma. open-label, none/not specified-controlled, adaptive. 224 participants.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Multiple myeloma
Trial Stage
Phase I/II
Drug Modality
ADC | Bispecific antibody | Small molecule

Key dates

Initial CTIS Submission Date
06-02-2024
First CTIS Authorization Date
14-05-2024

Trial design

open-label, none/not specified-controlled, adaptive Phase I/II trial in Spain, France, Germany.

Open Label
Yes
Comparator
None/Not specified
Adaptive
True, dose escalation design with determination of Recommended Phase 2 Dose (RP2D) (Phase Ia dose escalation and Phase Ib expansion/optimization modules).
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
224

Eligibility

Recruits 224 adults.

Inclusion criteria

  • {"criterion_text":"- Participants must be at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place.\n- Eastern Cooperative Oncology Group performance status of ≤ 2 in module 1, or 0 or 1 in modules 2 and 3\n- Documentation of Multiple Myeloma (MM) as defined by International Myeloma Working Group (IMWG) Diagnostic Criteria for Multiple Myeloma. Site should ensure that Multiple Myeloma diagnosis is confirmed in accordance with the IMWG Diagnostic Criteria\n- Participants must have one or more measurable disease criteria for Serum M-Protein, Urine M-protein, and Serum immunoglobulin free light chains as specified in the relevant module of the CSP;\n- Adequate organ and bone marrow function assessment at screening according to the hematological, hepatic, and renal parameters listed in the CSP as relevant to each module\n- Participants must have received at least 3 prior lines of treatment in module 1. In modules 2 and 3, participants must meet the phase-specific requirements for the number of prior lines of therapy.\n- The above is a summary of key criteria, other inclusion criteria details may apply"}

Exclusion criteria

  • {"criterion_text":"- Amyloidosis, plasma cell leukemia, Waldenstrom Macroglobulinemia, Polyneuropathy Organomegaly Endocrinopathy M-protein and Skin Syndrome, or Smoldering Multiple Myeloma (compliant with WHO criteria);\n- Participants who have previously received anti-GPRC5D or MMAE-containing treatment.\n- Participants with a history of prior malignancy other than MM within 3 years prior to first dose of study intervention. some exceptions apply\n- Participants with previous history of active John Cunningham virus infection resulting in PML\n- Participants with a known hypersensitivity to AZD0305 or any of the excipients of the product or to any of the drugs included in the respective modules or who experienced Grade 3 or higher hypersensitivity to prior monocloncal antibody therapy\n- Participants who have uncontrolled severe illness including but not limited to ongoing active infection requiring therapeutic antibiotics and/or other administration\n- The above is a summary of key criteria, other exclusion criteria details may apply\n- Participants who have previously received allogenic stem cell transplant, or participant has received autologous stem cell transplant within 3 months before the first dose of study intervention.\n- Participants exhibiting clinical signs of central nervous system involvement of MM;\n- Participants with known COPD, or previous history of ILD/pneumonitis\n- Participants with known moderate or severe persistent asthma within the past 5 years, or uncontrolled asthma of any classification;\n- Participants who have severe cardiovascular disease which is not adequately controlled.\n- Participants who have a history of immunodeficiency disease.\n- Participants with peripheral neuropathy ≥ Grade 2.\n- Primary refractory MM."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Occurrence of dose-limiting toxicities (Phase Ia dose escalation only).","definition_or_measurement_approach":"Occurrence of dose-limiting toxicities during Phase Ia dose escalation (no further definition provided in the available record)."}
  • {"endpoint_text":"- Incidence and severity of AEs and SAEs.","definition_or_measurement_approach":"Assessment of incidence and severity of adverse events (AEs) and serious adverse events (SAEs)."}
  • {"endpoint_text":"- these are the core primary endpoints of the study, module specific endpoints are available within the CSP","definition_or_measurement_approach":"Module-specific primary endpoints are available in the Clinical Study Plan (CSP); no further definition provided in the available record."}

Secondary endpoints

  • {"endpoint_text":"- Preliminary efficacy of AZD0305 according to IMWG 2016 response criteria as assessed by investigator, including response endpoints ORR, CRR (module 2 only), DoR, MRD negative CR rate (Modules 2 and 3 only), PFS, and OS.","definition_or_measurement_approach":"Efficacy assessed per IMWG 2016 response criteria by investigator, including ORR, CRR (module 2), DoR, MRD negative CR rate (modules 2 and 3), progression-free survival (PFS), overall survival (OS)."}
  • {"endpoint_text":"- PK parameters of AZD0305 (total ADC), total antibody (conjugated and unconjugated) and MMAE, including but not limited to AUC, Cmax, tmax, clearance, and half-life, as data allow.","definition_or_measurement_approach":"Measurement of PK parameters for AZD0305 (total ADC), total antibody and MMAE including AUC, Cmax, tmax, clearance, and half-life."}
  • {"endpoint_text":"- The number and percentage of participants who develop Anti-Drug Antibody (ADA).","definition_or_measurement_approach":"Count and percentage of participants developing anti-drug antibodies (ADA)."}
  • {"endpoint_text":"- These are the core secondary endpoints of the study, module specific endpoints are available within the CSP","definition_or_measurement_approach":"Module-specific secondary endpoints are available in the Clinical Study Plan (CSP); no further definition provided in the available record."}

Recruitment

Planned Sample Size
224
Recruitment Window Months
38
Consent Approach
Informed consent is provided by adult participants (participants must be at least 18 years of age). Subject information and informed consent forms (SIS and ICF) are available, including module-specific ICFs and documents for adult genomics and pregnant partners (separate ICF materials listed), indicating separate consent materials for genetic optional consent and pregnant partners.

Geography

Total Number Of Sites
14
Total Number Of Participants
68

Spain

Earliest CTIS Part Ii Submission Date
27-03-2024
Latest Decision Or Authorization Date
13-05-2026
Processing Time Days
777
Number Of Sites
5
Number Of Participants
18

Sites

Site Name
Hospital Germans Trias I Pujol
Department Name
Oncology
Principal Investigator Name
Albert Oriol Rocafiguera
Principal Investigator Email
aoriol@icooncologia.net
Contact Person Name
Albert Oriol Rocafiguera
Contact Person Email
aoriol@icooncologia.net
Site Name
Clinica Universidad De Navarra
Department Name
Hematology
Principal Investigator Name
Paula Rodriguez
Principal Investigator Email
paurodriguez@unav.es
Contact Person Name
Paula Rodriguez
Contact Person Email
paurodriguez@unav.es
Site Name
Hospital Universitario De Salamanca
Department Name
Hematology
Principal Investigator Name
Maria Victoria Mateos
Principal Investigator Email
mvmateos@usal.es
Contact Person Name
Maria Victoria Mateos
Contact Person Email
mvmateos@usal.es
Site Name
Hospital Universitario 12 De Octubre
Department Name
Hematology
Principal Investigator Name
Joaquin Martinez
Principal Investigator Email
jmarti01@med.ucm.es
Contact Person Name
Joaquin Martinez
Contact Person Email
jmarti01@med.ucm.es
Site Name
Clinica Universidad De Navarra (Pamplona)
Department Name
Hematology
Principal Investigator Name
Paula Rodriguez
Principal Investigator Email
paurodriguez@unav.es
Contact Person Name
Paula Rodriguez
Contact Person Email
paurodriguez@unav.es

France

Earliest CTIS Part Ii Submission Date
12-08-2024
Latest Decision Or Authorization Date
12-05-2026
Processing Time Days
638
Number Of Sites
2
Number Of Participants
20

Sites

Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Service d'hématologie clinique
Principal Investigator Name
Cyrille Touzeau
Principal Investigator Email
Cyrille.TOUZEAU@chu-nantes.fr
Contact Person Name
Cyrille Touzeau
Contact Person Email
Cyrille.TOUZEAU@chu-nantes.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Service d’Hématologie
Principal Investigator Name
Salomon Manier
Principal Investigator Email
salomon.manier@chu-lille.fr
Contact Person Name
Salomon Manier
Contact Person Email
salomon.manier@chu-lille.fr

Germany

Earliest CTIS Part Ii Submission Date
08-04-2024
Latest Decision Or Authorization Date
11-05-2026
Processing Time Days
763
Number Of Sites
7
Number Of Participants
30

Sites

Site Name
Universitaetsklinikum Essen AöR
Department Name
Klinik für Haematologie und Stammzelltransplantation
Principal Investigator Name
Amelie Boquoi
Principal Investigator Email
amelie.boquoi@uk-essen.de
Contact Person Name
Amelie Boquoi
Contact Person Email
amelie.boquoi@uk-essen.de
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Myeolomzentrum Klinik für hämatologie, Onkologie, Rheumatologie
Principal Investigator Name
Marc-Steffen Raab
Principal Investigator Email
marc.raab@med.uni-heidelberg.de
Contact Person Name
Marc-Steffen Raab
Site Name
Universitaetsklinikum Wuerzburg AöR
Department Name
Poliklinik MED II Haematologie Onkologie
Principal Investigator Name
Leo Rasche
Principal Investigator Email
rasche_l@ukw.de
Contact Person Name
Leo Rasche
Contact Person Email
rasche_l@ukw.de
Site Name
Klinikum Nuernberg
Department Name
Klinik fuer Innere Medizin 5
Principal Investigator Name
Stefan Knop
Principal Investigator Email
stefan.knop@klinikum-nuernberg.de
Contact Person Name
Stefan Knop
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Zentrum für Onkologie 2. Medizinische Klinik und Poliklinik
Principal Investigator Name
Katja Weisel
Principal Investigator Email
k.weisel@uke.de
Contact Person Name
Katja Weisel
Contact Person Email
k.weisel@uke.de
Site Name
Eberhard Karls Universitaet Tuebingen
Department Name
Klinik für Hämatologie und Stammzelltransplantation
Principal Investigator Name
Britta Besemer
Principal Investigator Email
Britta.Besemer@med.uni-tuebingen.de
Contact Person Name
Britta Besemer
Site Name
Universitaetsklinikum Schleswig-Holstein AöR
Department Name
Klinik für Haematologie und Onkologie
Principal Investigator Name
Cyrus Khandanpour
Principal Investigator Email
Cyrus.Khandanpour@uksh.de
Contact Person Name
Cyrus Khandanpour
Contact Person Email
Cyrus.Khandanpour@uksh.de

Sponsor

Primary sponsor

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

Investigational products

Investigational Product Name
AZD0305
Active Substance
AZD0305
Modality
ADC
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Investigational Product Name
ELRANATAMAB
Active Substance
ELRANATAMAB
Modality
Bispecific antibody
Routes Of Administration
SUBCUTANEOUS INJECTION
Route
SUBCUTANEOUS INJECTION
Investigational Product Name
POMALIDOMIDE
Active Substance
DIMETHYL FUMARATE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Combination Treatment
Yes

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