Clinical trial NCT05535244: A Study Evaluating the Efficacy and Safety of Cevostamab in Prior B Cell Maturation Antigen (BCMA)-Exposed Participants With Relapsed/Refractory Multiple Myeloma
Official title: A Phase I/II, Open-Label, Multi-Cohort Study to Evaluate the Efficacy and Safety of Cevostamab in Prior B Cell Maturation Antigen-Exposed Patients With Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-09-10
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


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

Primary outcomes:
measure: Objective Response Rate (ORR) as Determined by the Investigator
timeFrame: Baseline up to approximately 2 years
measure: Percentage of Participants with Adverse Events
timeFrame: Baseline up to approximately 2 years
Secondary outcomes:
measure: ORR as Determined by the Independent Review Committee (IRC)
timeFrame: Baseline up to approximately 2 years
measure: Duration of Response (DOR)
timeFrame: Baseline up to approximately 2 years
measure: Rate of Complete Response (CR) or Better
timeFrame: Baseline up to approximately 2 years
measure: Rate of Very Good Partial Response (VGPR) or Better
timeFrame: Baseline up to approximately 2 years
measure: Overall Survival (OS)
timeFrame: Baseline up until death from any cause (up to approximately 2 years)
measure: Progression-free Survival (PFS)
timeFrame: Baseline up to approximately 2 years
measure: Time to First Response (for Participants who Achieve an Objective Response)
timeFrame: Baseline up to approximately 2 years
measure: Time to Best Response (for Participants who Achieve an Objective Response)
timeFrame: Baseline up to approximately 2 years
measure: Percentage 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 (QLQ-C30) and EORTC QLQ-MY20
timeFrame: Baseline up to approximately 2 years
measure: Time to Deterioration in the Fatigue Domain of the EORTC QLQ-C30 and/or Disease Symptoms Domain of the EORTC QLQ-MY20
timeFrame: Baseline up to approximately 2 years
measure: Serum Concentration of Cevostamab at Specified Timepoints
timeFrame: At Cycles 1, 2, 3, 4, 6, 8 and every other cycle until the end of treatment up to approximately 2 years. Each cycle is 21-days.
measure: Number of Anti-drug Antibody (ADAs) Against Cevostamab at Baseline
timeFrame: Baseline
measure: Percentage of Participants with ADAs Against Cevostamab During the Study
timeFrame: Up to approximately 2 years
measure: Cytokine Release Syndrome (CRS) Following Administration of Tocilizumab
timeFrame: Baseline up to approximately 2 years
measure: Relationship Between Serum Concentration of Cevostamab and Cytokine Release
timeFrame: Baseline up to approximately 2 years
measure: Relationship Between Serum Concentration of Cevostamab and T Cell Number
timeFrame: Baseline up to approximately 2 years
measure: Relationship Between Serum Concentration of Cevostamab and T-cell Activation State
timeFrame: Baseline up to approximately 2 years
Other outcomes:
measure: Minimal Residual Disease (MRD) Negative Rate
timeFrame: Baseline up to approximately 2 years
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic-Jacksonville
state: Florida
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai (ISMMS)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Tennessee Oncology - Nashville
state: Tennessee
city: Salt Lake City
country: United States
facility: Hunstman Cancer Institute
state: Utah
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Nantes
country: France
facility: CHU NANTES - Hôtel Dieu
city: Paris
country: France
facility: APHP - Hospital Saint Louis
city: Poitiers
country: France
facility: CHU de Poitiers - La Miletrie
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II
city: Köln
country: Germany
facility: Klinik der Uni zu Köln
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Hospital
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel-Aviv
country: Israel
facility: Sourasky Medical Centre
city: Bologna
country: Italy
facility: Policlinico S.Orsola-Malpighi
state: Emilia-Romagna
city: Bergamo
country: Italy
facility: Asst Papa Giovanni Xxiii
state: Lombardia
city: Milano
country: Italy
facility: Fond. IRCCS Istituto Nazionale Tumori
state: Lombardia
city: Torino
country: Italy
facility: A.O. Città della Salute e della Scienza D - Osp. S. Giov. Battista Molinette
state: Piemonte
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial
city: Madrid
country: Spain
facility: Hospital Univ. 12 de Octubre
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: