Clinical trial • Phase I/II • Oncology

CEVOSTAMAB for Relapsed/Refractory Multiple myeloma

Phase I/II trial of CEVOSTAMAB for Relapsed/Refractory Multiple myeloma. open-label, none/not specified-controlled. 54 participants.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Relapsed/Refractory Multiple myeloma
Trial Stage
Phase I/II
Drug Modality
Bispecific antibody|Monoclonal antibody

Key dates

Initial CTIS Submission Date
06-06-2024
First CTIS Authorization Date
27-06-2024

Trial design

open-label, none/not specified-controlled Phase I/II trial in Belgium, France, Germany and others.

Open Label
Yes
Comparator
None/Not specified
Target Sample Size
54

Eligibility

Recruits 54 The record indicates vulnerable population selection (isVulnerablePopulationSelected: true). Subject information and informed consent forms are provided, including documents titled 'L1_SIS and ICF main and Appendix 1', 'L1_SIS and ICF pregnant partner', and 'L1_SIS and ICF infant', indicating age-specific consent/I C F materials are available..

Pregnancy Exclusion
Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 5 months after the final dose of cevostamab or within 3 months after the last dose of tocilizumab
Vulnerable Population
The record indicates vulnerable population selection (isVulnerablePopulationSelected: true). Subject information and informed consent forms are provided, including documents titled 'L1_SIS and ICF main and Appendix 1', 'L1_SIS and ICF pregnant partner', and 'L1_SIS and ICF infant', indicating age-specific consent/I C F materials are available.

Inclusion criteria

  • {"criterion_text":"- Documented diagnosis of multiple myeloma (MM) based on standard International Myeloma Working Group (IMWG) criteria"}
  • {"criterion_text":"- Evidence of progressive disease based on investigators determination of response by IMWG criteria on or after their last dosing regimen"}
  • {"criterion_text":"- Prior B cell maturation antigen (BCMA) antibody-drug conjugate (ADC) or chimeric antigen receptor T (CAR-T) Cohort: participants who have received a BCMA-targeted CAR-T or ADC therapy and are triple-class relapsed or refractory"}
  • {"criterion_text":"- Prior BCMA Bispecific Cohort: participants who have received a BCMA-targeting T-cell-dependent bispecific (TDB) antibody and are triple-class relapsed or refractory"}
  • {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1"}
  • {"criterion_text":"- Life expectancy is at least 12 weeks"}

Exclusion criteria

  • {"criterion_text":"- Inability to comply with protocol-mandated hospitalization"}
  • {"criterion_text":"- Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 5 months after the final dose of cevostamab or within 3 months after the last dose of tocilizumab"}
  • {"criterion_text":"- Prior treatment with cevostamab or another agent with the same target"}
  • {"criterion_text":"- Prior BCMA ADC or CAR-T Cohort: prior treatment with any T cell dependent bi‑specific antibody (TDB) antibody including non BCMA targeting TDB"}
  • {"criterion_text":"- Prior BCMA Bispecific Cohort: treatment with TDB antibody within 12 weeks prior to enrollment in the study"}
  • {"criterion_text":"- Prior use of any monoclonal antibody (mAb), radioimmunoconjugate, or ADC as anti-cancer therapy within 4 weeks before first study treatment, except for the use of non-myeloma therapy"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 1. ORR, defined as the proportion of participants with an objective response [stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR)], based on investigator-assessed response, according to IMWG criteria","definition_or_measurement_approach":"ORR defined as proportion of participants with sCR, CR, VGPR, or PR based on investigator-assessed response according to International Myeloma Working Group (IMWG) criteria."}
  • {"endpoint_text":"- 2. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) for CRS and of immune effector cell associated neurotoxicity syndrome (ICANS) grading","definition_or_measurement_approach":"Incidence and severity graded per NCI CTCAE v5.0; cytokine release syndrome (CRS) and ICANS graded per ASTCT criteria."}

Secondary endpoints

  • {"endpoint_text":"- 1. ORR, defined as the proportion of participants with an objective response based on independent review committee (IRC)-assessed response","definition_or_measurement_approach":"ORR based on independent review committee (IRC) assessment."}
  • {"endpoint_text":"- 2. Duration of response (DOR), defined as the time from the first occurrence of an objective response until the date of disease progression or death from any cause (whichever occurs first), as determined separately by the IRC and the investigator","definition_or_measurement_approach":"Time from first objective response to disease progression or death (whichever first), assessed separately by IRC and investigator."}
  • {"endpoint_text":"- 3. Rate of CR or better, defined as the proportion of participants who achieve a response of sCR or CR, as assessed separately by IRC and the investigator","definition_or_measurement_approach":"Proportion achieving sCR or CR, assessed separately by IRC and investigator."}
  • {"endpoint_text":"- 4. Rate of VGPR or better, defined as the proportion of participants who achieve a response of VGPR or better, as assessed separately by IRC and the investigator","definition_or_measurement_approach":"Proportion achieving VGPR or better, assessed separately by IRC and investigator."}
  • {"endpoint_text":"- 5. Overall survival (OS), defined as the time from initiation of study treatment to death from any cause","definition_or_measurement_approach":"Time from treatment start to death from any cause."}
  • {"endpoint_text":"- 6. Progression-free survival (PFS), defined as the time from initiation of study treatment to the first occurrence of disease progression, relapse, or death from any cause (whichever occurs first), as assessed separately by IRC and the investigator","definition_or_measurement_approach":"Time from treatment start to first disease progression, relapse, or death, assessed separately by IRC and investigator."}
  • {"endpoint_text":"- 7. Time to first response (for participants who achieve an objective response), defined as time from initiation of study treatment to first achieving an objective response (separate analyses by IRC and investigator)","definition_or_measurement_approach":"Time from treatment initiation to first objective response; analyses by IRC and investigator."}
  • {"endpoint_text":"- 8. Time to best response (for participants who achieve an objective response), defined as time from initiation of study treatment to achieving the deepest response (separate analyses by IRC and investigator)","definition_or_measurement_approach":"Time from treatment initiation to deepest response; analyses by IRC and investigator."}
  • {"endpoint_text":"- 9. Proportion of participants experiencing a clinically meaningful improvement in the fatigue domain of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core-30 Questionnaire (QLQC-30) and EORTC QLQ-MY20","definition_or_measurement_approach":"Proportion with clinically meaningful improvement in EORTC QLQ-C30 fatigue domain and EORTC QLQ-MY20."}
  • {"endpoint_text":"- 10. Time to deterioration in the fatigue domain of the EORTC QLQ-C30 and/or disease symptoms domain of the EORTC QLQ-MY20","definition_or_measurement_approach":"Time to deterioration in EORTC QLQ-C30 fatigue domain and/or EORTC QLQ-MY20 disease symptoms domain."}
  • {"endpoint_text":"- 11. Serum concentration of cevostamab at specified timepoints","definition_or_measurement_approach":"Serum concentration measurements of cevostamab at predefined timepoints."}
  • {"endpoint_text":"- 12. Pharmacokinetics (PK) parameters of cevostamab, as data allow","definition_or_measurement_approach":"PK parameter estimation for cevostamab according to available data."}
  • {"endpoint_text":"- 13. Prevalence of anti-drug antibodies (ADAs) against cevostamab at baseline and incidence of ADAs against cevostamab during the study","definition_or_measurement_approach":"Assessment of ADAs at baseline and incidence during study."}
  • {"endpoint_text":"- 14. CRS outcome following administration of tocilizumab (e.g., time to CRS resolution, doses of tocilizumab administered, relationship between serum concentration or other PK parameters for tocilizumab and pharmacodynamic biomarkers)","definition_or_measurement_approach":"Outcomes following tocilizumab treatment for CRS including time to CRS resolution, tocilizumab doses, and PK/PD relationships."}
  • {"endpoint_text":"- 15. Relationship between serum concentration or other PK parameters for cevostamab and pharmacodynamic biomarkers, including, but not limited to, cytokine release, T cell number, and T-cell activation state","definition_or_measurement_approach":"Correlation analyses between cevostamab PK parameters and PD biomarkers (cytokines, T-cell number and activation)."}
  • {"endpoint_text":"- 16. Relationship between biomarkers in blood, bone marrow biopsies and aspirates, and tumor tissue and efficacy, safety, PK, immunogenicity, or other biomarker endpoints","definition_or_measurement_approach":"Relationship analyses between tissue/blood/marrow biomarkers and efficacy, safety, PK, immunogenicity, or other biomarker endpoints."}

Recruitment

Planned Sample Size
54
Recruitment Window Months
48
Consent Approach
Informed consent via subject information and informed consent forms (documents listed in the record: 'L1_SIS and ICF main and Appendix 1', 'L1_SIS and ICF pregnant partner', 'L1_SIS and ICF infant', and a privacy consent form). Age-specific ICFs are indicated by the presence of an 'infant' ICF and a 'pregnant partner' ICF; the main contact for trial information is provided as 'Trial Information System - TISL' (global.eudract@roche.com).

Geography

Total Number Of Sites
18
Total Number Of Participants
38

Belgium

Earliest CTIS Part Ii Submission Date
16-05-2023
Latest Decision Or Authorization Date
27-06-2024
Processing Time Days
408
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
UZ Leuven
Department Name
Hematology
Contact Person Name
Michel Delforge
Contact Person Email
michel.delforge@uzleuven.be

France

Earliest CTIS Part Ii Submission Date
16-05-2023
Latest Decision Or Authorization Date
02-07-2024
Processing Time Days
413
Number Of Sites
3
Number Of Participants
5

Sites

Site Name
Centre Hospitalier Universitaire De Poitiers
Department Name
Oncologie hematologique - Pole Regional de Cancerologie
Contact Person Name
Xavier Leleu
Contact Person Email
xavier.leleu@chu-poitiers.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Service d'Hematologie
Contact Person Name
Cyrille Touzeau
Contact Person Email
cyrille.touzeau@chu-nantes.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Service d'Immunologie Hématologie
Contact Person Name
Bertrand Arnulf
Contact Person Email
bertrand.arnulf@aphp.fr

Germany

Earliest CTIS Part Ii Submission Date
16-05-2023
Latest Decision Or Authorization Date
01-07-2024
Processing Time Days
412
Number Of Sites
5
Number Of Participants
6

Sites

Site Name
Universitätsklinikum Würzburg
Department Name
Med. Klinik und Poliklinik II, Zentrum für Innere Medizin
Contact Person Name
Martin Kortüm
Contact Person Email
hoxha_e@ukw.de
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Onkologisches Zentrum, Medizinische Klinik II
Contact Person Name
Katja Weisel
Contact Person Email
k.weisel@uke.de
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Med. Klinik und Poliklinik, Innere Medizin II
Contact Person Name
Britta Besemer
Site Name
University Hospital Cologne AöR
Department Name
Centrum für integrierte Onkologie, Studienzentrum der Klinik I für Innere Medizin
Contact Person Name
Christoph Scheid
Contact Person Email
christoph.scheid@uk-koeln.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Charité Centrum 14, Med. Klinik für Hämatologie und Onkologie
Contact Person Name
Jan Krönke
Contact Person Email
jan.kroenke@charite.de

Spain

Earliest CTIS Part Ii Submission Date
16-05-2023
Latest Decision Or Authorization Date
28-06-2024
Processing Time Days
409
Number Of Sites
5
Number Of Participants
8

Sites

Site Name
Hospital Universitario 12 De Octubre
Department Name
Servicio de Hematología
Contact Person Name
Joaquín Martínez López
Contact Person Email
jmarti01@ucm.es
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Servicio de Hematología
Contact Person Name
Javier de la Rubia Comos
Contact Person Email
delarubia_jav@gva.es
Site Name
Clinica Universidad De Navarra
Department Name
Servicio de Hematología
Contact Person Name
Paula Rodríguez Otero
Contact Person Email
paurodriguez@unav.es
Site Name
Hospital Clinic De Barcelona
Department Name
Servicio de Hematología
Contact Person Name
Laura Rosiñol Dachs
Contact Person Email
lrosinol@clinic.cat
Site Name
Clinica Universidad De Navarra (Pamplona)
Department Name
Servicio de Hematología
Contact Person Name
Paula Rodríguez Otero
Contact Person Email
paurodriguez@unav.es

Italy

Earliest CTIS Part Ii Submission Date
16-05-2023
Latest Decision Or Authorization Date
10-12-2025
Processing Time Days
939
Number Of Sites
4
Number Of Participants
15

Sites

Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
U.O.C. Ematologia
Contact Person Name
Elena Zamagni
Contact Person Email
e.zamagni@unibo.it
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
S.C. Ematologia
Contact Person Name
Paolo Corradini
Contact Person Email
paolo.corradini@unimi.it
Site Name
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
Department Name
UOC Ematologia
Contact Person Name
Monica Galli
Contact Person Email
monicagalli@asst-pg23.it
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
S.C. di Ematologia
Contact Person Name
Giulia Benevolo

Sponsor

Primary sponsor

Full Name
F. Hoffmann-La Roche AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
Greenphire LLC
Responsibilities
Patient expenses reimbursement USA, Belgium
Name
Iqvia Inc.
Responsibilities
Monitoring
Name
Labcorp Central Laboratory Services LP
Name
Almac Clinical Technologies LLC
Name
Bioclinica Inc.
Responsibilities
Independent Central Reviewer

Third parties

  • {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient expenses reimbursement USA, Belgium","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Iqvia Inc.","duties_or_roles":"Monitoring","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Independent Central Reviewer","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
Cevostamab
Active Substance
CEVOSTAMAB
Modality
Bispecific antibody
Routes Of Administration
IV INFUSION
Route
IV INFUSION
Authorisation Status
Investigational (not authorised)
Investigational Product Name
RoActemra 20 mg/mL concentrate for solution for infusion
Active Substance
TOCILIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
IV INFUSION
Route
IV INFUSION
Authorisation Status
Authorised (EU/1/08/492/003)
Combination Treatment
Yes

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