A Study to Evaluate the Efficacy and Safety of Cevostamab in Prior B Cell Maturation Antigen-Exposed Patients with Relapsed/Refractory Multiple Myeloma

Phase 1

Conditions: Relapsed/Refractory Multiple Myeloma
MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2021-006816-10-DE

Lead Sponsor: F. Hoffman-La Roche Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 140

Inclusion Criteria

• Age >= 18 years
• Documented diagnosis of multiple myeloma (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 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
• Prior BCMA Bispecific Cohort: participants who have received a BCMAtargeting 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 adverse events from prior anti-cancer therapy to Grade =< 1
• Measurable disease, defined as at least one of the following:
– Serum M-protein >= 0.5 g/dL (>= 5 g/L)
– Urine M-protein >= 200 mg/24 hours
– Serum-free light chain (sFLC) assay: involved sFLCs >= 10 mg/dL (>=100 mg/L) and an abnormal sFLC ratio (< 0.26 or > 1.65)
– If central laboratory assessments are not available, relevant local laboratory measurements must exceed the minimum required level by at least 25%
• Adequate laboratory values
• 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

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 within 3 months after the last dose of tocilizumab
• 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 bispecific antibody (TDB) antibody including non BCMA targeting TDB
• Prior BCMA Bispecific Cohort: treatment with TDB antibody within 12 weeks prior to enrollment in the study
• 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 as follows:
– Prior PD-L1/PD-1 or CTLA-4 inhibitor: Grade >= 3 adverse events with the exception of Grade 3 endocrinopathy managed with replacement therapy
– Grade 1-2 adverse events that did not resolve to baseline after treatment discontinuation
• Treatment with radiotherapy, any chemotherapeutic agent, or treatment with any other anti-cancer agent within 4 weeks or 5 halflives 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, lowgrade, 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 coronavirus disease 2019 (COVID-19) infection at study enrollment or requiring treatment with IV antiviral where last dose of IV antiviral treatment was given within 14 days prior to first study treatment. Patients 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 quantifiabl

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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