Clinical trial NCT06934044: A Study Evaluating the Pharmacokinetics, Safety, and Efficacy of Cevostamab in Chinese Participants With Relapsed or Refractory Multiple Myeloma
Official title: A Phase Ib, Open-Label, Single-Arm, Multicenter Trial Evaluating the Pharmacokinetics, Safety, and Efficacy of Cevostamab in Chinese Patients With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2025-04-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate the pharmacokinetics (PK), safety, and efficacy of cevostamab in participants with relapsed or refractory (R/R) multiple myeloma (MM).


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
* Current relapsed or refractory (R/R) disease status
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Life expectancy of 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 or better
* 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:

* Unable 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 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, including but not limited to, cytokine therapy and anti-CTLA-4, anti-PD-1, and anti-PD-L1
* 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
* 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.
* 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 hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
* Known history of Grade \>=3 CRS or immune effector cell-associated neurotoxicity syndrome (ICANS) with prior bispecific therapies
* 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: Serum Concentration of Cevostamab at Specified Timepoints
timeFrame: Cycle 1 Day 1 (C1D1) up to approximately 2 years. Each cycle=21 days
measure: Percentage of Participants with Adverse Events
timeFrame: Baseline up to approximately 2 years
Secondary outcomes:
measure: Objective Response Rate (ORR)
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: Duration of Response (DOR)
timeFrame: Baseline up to approximately 2 years
measure: Progression-free Survival (PFS)
timeFrame: Start of study treatment to first date of disease progression, relapse or death from any cause, whichever occurs first (up to approximately 2 years)
measure: Time to First Response (for Participants who Achieve a Response of Partial Response (PR) or Better)
timeFrame: Baseline up to approximately 2 years
measure: Time to Best Response (for Participants who Achieve a Response of PR 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: Minimal Residual Disease (MRD) Negativity (for Participants who Achieve a Response of CR or Better)
timeFrame: Baseline up to approximately 2 years
measure: MRD Negativity (for all Efficacy-evaluable Participants)
timeFrame: Baseline up to approximately 2 years
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: Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Treatment Toxicities Assessed by NCI Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)
timeFrame: Up to approximately 2 years
measure: Number of Participants Reporting Each Response Option for Treatment Side-effect Bother Single-item General Population, Question 5 (GP5) from the Functional Assessment of Cancer Therapy-General Questionnaire; (FACT-G)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Institute of Hematology & Blood Diseases Hospital
state: Tianjin
city: Wenzhou City
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: