Trial Title:
A Study Evaluating the Efficacy and Safety of Cevostamab in Prior B Cell Maturation Antigen (BCMA)-Exposed Participants With Relapsed/Refractory Multiple Myeloma
NCT ID:
NCT05535244
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cevostamab
Description:
Cevostamab will be administered by IV infusion in 21-day cycles.
Arm group label:
Cohort A1: Prior BCMA antibody-drug conjugate (ADC) or chimeric antigen receptor T (CAR-T)
Arm group label:
Cohort A2: Prior BCMA Bispecific
Arm group label:
Cohort B1: Prior BCMA CAR-T
Arm group label:
Cohort B2: Prior BCMA Bispecific
Intervention type:
Drug
Intervention name:
Tocilizumab
Description:
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS)
when necessary.
Arm group label:
Cohort A1: Prior BCMA antibody-drug conjugate (ADC) or chimeric antigen receptor T (CAR-T)
Arm group label:
Cohort A2: Prior BCMA Bispecific
Arm group label:
Cohort B1: Prior BCMA CAR-T
Arm group label:
Cohort B2: Prior BCMA Bispecific
Summary:
This study will evaluate the efficacy, safety, and pharmacokinetics of cevostamab in
participants with relapsed or refractory multiple myeloma (R/R MM) via intravenous (IV)
infusion.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Documented diagnosis of MM based on standard International Myeloma Working Group
(IMWG) criteria
- Evidence of progressive disease based on investigators determination of response by
IMWG criteria on or after their last dosing regimen
- Prior BCMA ADC or CAR-T Cohort: participants who have received a BCMA-targeted CAR-T
or ADC therapy and are triple-class relapsed or refractory
- Prior BCMA Bispecific Cohort: participants who have received a BCMA-targeting
T-cell-dependent bispecific (TDB) antibody and are triple-class relapsed or
refractory
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Life expectancy is at least 12 weeks
- Agreement to protocol-specified assessments, including bone marrow biopsy and
aspirate samples as detailed in the protocol
- Resolution of AEs from prior anti-cancer therapy to Grade =< 1
- For female participants of childbearing potential: agreement to remain abstinent
(refrain from heterosexual intercourse) or use contraception during the treatment
period and for at least 5 months after the final dose of cevostamab and for 3 months
after the last dose of tocilizumab was administered
- For male participants: agreement to remain abstinent (refrain from heterosexual
intercourse) or use a condom, and agree to refrain from donating sperm during the
treatment period and for at least 2 months after the final dose of tocilizumab (if
applicable) to avoid exposing the embryo
Exclusion Criteria:
- Inability to comply with protocol-mandated hospitalization
- Pregnancy or breastfeeding, or intention of becoming pregnant during the study or
within 5 months after the final dose of cevostamab or tocilizumab or within 3 months
after the last dose of tocilizumab (if applicable)
- Prior treatment with cevostamab or another agent with the same target
- Prior BCMA ADC or CAR-T Cohort: prior treatment with any T cell dependent
bi-specific antibody (TDB) antibody including non BCMA targeting TDB
- 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
- Prior treatment with systemic immunotherapeutic agents
- Prior treatment with CAR-T cell therapy within 12 weeks before first cevostamab
infusion
- Known treatment-related, immune-mediated adverse events associated with prior
checkpoint inhibitors
- Treatment with radiotherapy, any chemotherapeutic agent, or treatment with any other
anti-cancer agent within 4 weeks or 5 half-lives of the drug, whichever is shorter,
prior to first study treatment
- Autologous stem cell transplantation (SCT) within 100 days prior to first study
treatment
- Prior allogeneic SCT
- Circulating plasma cell count exceeding 500/ microliter (µL) or 5% of the peripheral
blood white cells
- Prior solid organ transplantation
- History of autoimmune disease
- History of confirmed progressive multifocal leukoencephalopathy
- History of severe allergic or anaphylactic reactions to mAb therapy
- Known history of amyloidosis
- Lesions in proximity of vital organs that may develop sudden
decompensation/deterioration in the setting of a tumor flare
- History of other malignancy within 2 years prior to screening, except those with
negligible risk of metastasis or death, such as ductal carcinoma in situ not
requiring chemotherapy, appropriately treated carcinoma in situ of the cervix,
non-melanoma skin carcinoma, low-grade, localized prostate cancer not requiring
treatment or appropriately treated Stage I uterine cancer
- Current or past history of central nervous system (CNS) disease, such as stroke,
epilepsy, CNS vasculitis, neurodegenerative disease, or CNS involvement by MM
- Significant cardiovascular disease that may limit a potential participant's ability
to adequately respond to a cytokine release syndrome (CRS) event
- Symptomatic active pulmonary disease or requiring supplemental oxygen
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
at study enrollment, or any major episode of infection requiring treatment with IV
(intravenous) antimicrobials where the last dose of IV antimicrobial was given
within 14 days prior to first study treatment
- Active symptomatic COVID-19 infection at study enrollment or requiring treatment
with IV antiviral where the last dose of IV antiviral treatment was given within 14
days prior to first study treatment. Participants with active COVID-19 infection
must have clinical recovery and two negative antigen tests at least 24 hours apart
prior to first study treatment
- Positive and quantifiable Epstein-Barr virus (EBV) polymerase chain reaction (PCR)
or cytomegalovirus (CMV) PCR prior to first study treatment
- Known or suspected chronic active EBV infection
- Known history of Grade >=3 CRS or immune effector cell-associated neurotoxicity
syndrome (ICANS) with prior bispecific therapies
- Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation
syndrome (MAS)
- Recent major surgery within 4 weeks prior to first study treatment
- Positive serologic or PCR test results for acute or chronic hepatitis B virus (HBV)
infection
- Acute or chronic hepatitis C virus (HCV) infection
- Known history of human immunodeficiency virus (HIV) seropositivity
- Administration of a live, attenuated vaccine within 4 weeks before first study
treatment or anticipation that such a live attenuated vaccine will be required
during the study
- Treatment with systemic immunosuppressive medications, with the exception of
corticosteroid treatment <= 10 mg/day prednisone or equivalent, within 2 weeks prior
to first study treatment
- History of illicit drug or alcohol abuse within 12 months prior to screening, in the
investigator's judgment
- Any medical condition or abnormality in clinical laboratory tests that, in the
investigator's judgment, precludes the participant's safe participation in and
completion of the study, or which could affect compliance with the protocol or
interpretation of results
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic - Arizona
Address:
City:
Phoenix
Zip:
85054
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Colorado
Address:
City:
Aurora
Zip:
80045-2517
Country:
United States
Status:
Recruiting
Facility:
Name:
Mayo Clinic-Jacksonville
Address:
City:
Jacksonville
Zip:
32224
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Maryland Greenebaum Cancer Center
Address:
City:
Baltimore
Zip:
21201
Country:
United States
Status:
Recruiting
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Facility:
Name:
Mayo Clinic - Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Facility:
Name:
Icahn School of Medicine at Mount Sinai (ISMMS); The Derald H. Ruttenberg Treatment Center
Address:
City:
New York
Zip:
10029
Country:
United States
Status:
Recruiting
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Active, not recruiting
Facility:
Name:
Tennessee Oncology - Nashville
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Active, not recruiting
Facility:
Name:
Methodist Hospital
Address:
City:
San Antonio
Zip:
78229
Country:
United States
Status:
Recruiting
Facility:
Name:
Hunstman Cancer Institute
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Facility:
Name:
Calvary Mater Newcastle; Hematology
Address:
City:
Waratah
Zip:
2298
Country:
Australia
Status:
Recruiting
Facility:
Name:
St Vincent's Hospital Melbourne
Address:
City:
Fitzroy
Zip:
3065
Country:
Australia
Status:
Recruiting
Facility:
Name:
UZ Leuven Gasthuisberg
Address:
City:
Leuven
Zip:
3000
Country:
Belgium
Status:
Recruiting
Facility:
Name:
CHU NANTES - Hôtel Dieu; Service d'Hematologie Clinique
Address:
City:
Nantes
Zip:
44093
Country:
France
Status:
Recruiting
Facility:
Name:
APHP - Hospital Saint Louis
Address:
City:
Paris
Zip:
75475
Country:
France
Status:
Recruiting
Facility:
Name:
CHU de Poitiers - La Miletrie; Oncologie hematologique - Pole Regional de Cancerologie
Address:
City:
Poitiers
Zip:
86021
Country:
France
Status:
Recruiting
Facility:
Name:
CAMPUS BENJAMIN FRANKLIN CharitéCentrum 14 Med.Klinik f.Hämatologie u.Onkologie
Address:
City:
Berlin
Zip:
12200
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II
Address:
City:
Hamburg
Zip:
20246
Country:
Germany
Status:
Active, not recruiting
Facility:
Name:
Klinik der Uni zu Köln; Klinik für Innere Medizin
Address:
City:
Köln
Zip:
50924
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitätsklinikum Tübingen Medizinische UNI-Klinik und Poliklinik Abt. Innere Medizin II
Address:
City:
Tübingen
Zip:
72076
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitätsklinikum Würzburg; Medizinische Klinik und Poliklinik II; Hämatologie / Onkologie
Address:
City:
Würzburg
Zip:
97080
Country:
Germany
Status:
Recruiting
Facility:
Name:
Hadassah Ein Karem Hospital; Haematology
Address:
City:
Jerusalem
Zip:
9112001
Country:
Israel
Status:
Recruiting
Facility:
Name:
Sheba Medical Center; Tel Hashomer
Address:
City:
Ramat Gan
Zip:
5262100
Country:
Israel
Status:
Recruiting
Facility:
Name:
Sourasky Medical Centre
Address:
City:
Tel-Aviv
Zip:
6423906
Country:
Israel
Status:
Recruiting
Facility:
Name:
Policlinico S.Orsola-Malpighi;Istituto di Ematologia "Seragnoli"
Address:
City:
Bologna
Zip:
40138
Country:
Italy
Status:
Recruiting
Facility:
Name:
ASST PAPA GIOVANNI XXIII; Ematologia
Address:
City:
Bergamo
Zip:
24127
Country:
Italy
Status:
Recruiting
Facility:
Name:
Fond. IRCCS Istituto Nazionale Tumori; S. C. Ematologia
Address:
City:
Milano
Zip:
20133
Country:
Italy
Status:
Recruiting
Facility:
Name:
A.O. Città della Salute e della Scienza D - Osp. S. Giov. Battista Molinette; Ematologia I
Address:
City:
Torino
Zip:
10126
Country:
Italy
Status:
Recruiting
Facility:
Name:
Clinica Universitaria de Navarra; Servicio de Hematologia
Address:
City:
Pamplona
Zip:
31008
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Clínic i Provincial; Servicio de Hematología y Oncología
Address:
City:
Barcelona
Zip:
08036
Country:
Spain
Status:
Active, not recruiting
Facility:
Name:
Clinica Universidad de Navarra Madrid; Servicio de Hematología
Address:
City:
Madrid
Zip:
28027
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Univ. 12 de Octubre; Servicio de Hematologia
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario la Fe; Servicio de Hematologia
Address:
City:
Valencia
Zip:
46026
Country:
Spain
Status:
Recruiting
Start date:
October 18, 2022
Completion date:
February 26, 2027
Lead sponsor:
Agency:
Hoffmann-La Roche
Agency class:
Industry
Source:
Hoffmann-La Roche
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05535244
