A Study Evaluating the Efficacy and Safety of Cevostamab in Prior B Cell Maturation Antigen (BCMA)-Exposed Participants With Relapsed/Refractory Multiple Myeloma

NCT05535244 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: CO434762021-006816-10
• Study Type: interventional
• Target: 90
• Locations: 8 countries
• Sites: 26

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR) as Determined by the Investigator

  Baseline up to approximately 2 years

• Percentage of Participants with Adverse Events

  Baseline up to approximately 2 years

Secondary Outcomes (17)

• ORR as Determined by the Independent Review Committee (IRC)

  Baseline up to approximately 2 years

• Duration of Response (DOR)

  Baseline up to approximately 2 years

• Rate of Complete Response (CR) or Better

  Baseline up to approximately 2 years

• Rate of Very Good Partial Response (VGPR) or Better

  Baseline up to approximately 2 years

• Overall Survival (OS)

  Baseline up until death from any cause (up to approximately 2 years)

Other Outcomes (1)

• Minimal Residual Disease (MRD) Negative Rate

  Baseline up to approximately 2 years

Study Arms (4)

Cohort A1: Prior BCMA antibody-drug conjugate (ADC) or chimeric antigen receptor T (CAR-T)

EXPERIMENTAL

Participants in Cohort A1 will be treated at the double step-up split dosing regimen.

Drug: Cevostamab; Drug: Tocilizumab

Cohort A2: Prior BCMA Bispecific

EXPERIMENTAL

Participants enrolled into exploratory Cohort A2 will receive the same dosing regimen as Cohort A1.

Drug: Cevostamab; Drug: Tocilizumab

Cohort B1: Prior BCMA CAR-T

EXPERIMENTAL

Participants enrolled in expansion Cohort B1, will be given cevostamab at the selected dosing regimen.

Drug: Cevostamab; Drug: Tocilizumab

Cohort B2: Prior BCMA Bispecific

EXPERIMENTAL

Expansion Cohort B2 will be opened, after the initial results from Cohort A2, at the same dose as per Cohort B1.

Drug: Cevostamab; Drug: Tocilizumab

Interventions

Cevostamab DRUG

Cevostamab will be administered by IV infusion in 21-day cycles.

Cohort A1: Prior BCMA antibody-drug conjugate (ADC) or chimeric antigen receptor T (CAR-T); Cohort A2: Prior BCMA Bispecific; Cohort B1: Prior BCMA CAR-T; Cohort B2: Prior BCMA Bispecific

Tocilizumab DRUG

Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.

Cohort A1: Prior BCMA antibody-drug conjugate (ADC) or chimeric antigen receptor T (CAR-T); Cohort A2: Prior BCMA Bispecific; Cohort B1: Prior BCMA CAR-T; Cohort B2: Prior BCMA Bispecific

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (26)

University of Colorado

Aurora, Colorado, 80045-2517, United States

Location

Mayo Clinic-Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Tennessee Oncology - Nashville

Nashville, Tennessee, 37203, United States

Location

Hunstman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

CHU NANTES - Hôtel Dieu

Nantes, 44093, France

Location

APHP - Hospital Saint Louis

Paris, 75475, France

Location

CHU de Poitiers - La Miletrie

Poitiers, 86021, France

Location

Klinik der Uni zu Köln

Cologne, 50924, Germany

Location

Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II

Hamburg, 20246, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

Hadassah Ein Karem Hospital

Jerusalem, 9112001, Israel

Location

Sheba Medical Center

Ramat Gan, 5262100, Israel

Location

Sourasky Medical Centre

Tel Aviv, 6423906, Israel

Location

Policlinico S.Orsola-Malpighi

Bologna, Emilia-Romagna, 40138, Italy

Location

Asst Papa Giovanni Xxiii

Bergamo, Lombardy, 24127, Italy

Location

Fond. IRCCS Istituto Nazionale Tumori

Milan, Lombardy, 20133, Italy

Location

A.O. Città della Salute e della Scienza D - Osp. S. Giov. Battista Molinette

Turin, Piedmont, 10126, Italy

Location

Hospital Clínic i Provincial

Barcelona, 08036, Spain

Location

Hospital Univ. 12 de Octubre

Madrid, 28041, Spain

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2022
• First Posted: September 10, 2022
• Study Start: October 17, 2022
• Primary Completion (Estimated): February 26, 2027
• Study Completion (Estimated): February 26, 2027
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

IT (4); DE (3); ES (2); US (8); FR (3); AU (2); BE (1); IL (3)