A Study Evaluating the Efficacy and Safety of Cevostamab in Prior B Cell Maturation Antigen (BCMA)-Exposed Participants With Relapsed/Refractory Multiple Myeloma (CAMMA 2)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Tocilizumab; Drug: Cevostamab

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
• France
  • Nantes, France, 44093
    • CHU Nantes - Hotel Dieu
  • Paris, France, 75475
    • APHP - Hospital Saint Louis
  • Poitiers, France, 86021
    • CHU de Poitiers - La Miletrie
• Germany
  • Cologne, Germany, 50924
    • Klinik der Uni zu Köln
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II
  • Würzburg, Germany, 97080
    • Universitatsklinikum Wurzburg
• Israel
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Karem Hospital
  • Ramat Gan, Israel, 5262100
    • Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Centre
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Policlinico S.Orsola-Malpighi
  • Lombardy
    • Bergamo, Lombardy, Italy, 24127
      • Asst Papa Giovanni XXIII
    • Milan, Lombardy, Italy, 20133
      • Fond. IRCCS Istituto Nazionale Tumori
  • Piedmont
    • Turin, Piedmont, Italy, 10126
      • A.O. Città della Salute e della Scienza D - Osp. S. Giov. Battista Molinette
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial
  • Madrid, Spain, 28041
    • Hospital Univ. 12 de Octubre
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045-2517
      • University of Colorado
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic-Jacksonville
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenebaum Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai (ISMMS)
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology - Nashville
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Hunstman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A1: Prior BCMA antibody-drug conjugate (ADC) or chimeric antigen receptor T (CAR-T); Participants in Cohort A1 will be treated at the double step-up split dosing regimen.	Drug: Tocilizumab; Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.; Drug: Cevostamab; Cevostamab will be administered by IV infusion in 21-day cycles.
Experimental: Cohort A2: Prior BCMA Bispecific; Participants enrolled into exploratory Cohort A2 will receive the same dosing regimen as Cohort A1.	Drug: Tocilizumab; Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.; Drug: Cevostamab; Cevostamab will be administered by IV infusion in 21-day cycles.
Experimental: Cohort B2: Prior BCMA Bispecific; Expansion Cohort B2 will be opened, after the initial results from Cohort A2, at the same dose as per Cohort B1.	Drug: Tocilizumab; Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.; Drug: Cevostamab; Cevostamab will be administered by IV infusion in 21-day cycles.
Experimental: Cohort B1: Prior BCMA CAR-T; Participants enrolled in expansion Cohort B1, will be given cevostamab at the selected dosing regimen.	Drug: Tocilizumab; Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.; Drug: Cevostamab; Cevostamab will be administered by IV infusion in 21-day cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Adverse Events	Baseline up to approximately 2 years
Objective Response Rate (ORR) as Determined by the Investigator	Baseline up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Anti-drug Antibody (ADAs) Against Cevostamab at Baseline	Baseline
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)
Progression-free Survival (PFS)	Baseline up to approximately 2 years
Time to First Response (for Participants who Achieve an Objective Response)	Baseline up to approximately 2 years
Time to Best Response (for Participants who Achieve an Objective Response)	Baseline up to approximately 2 years
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	Baseline up to approximately 2 years
Time to Deterioration in the Fatigue Domain of the EORTC QLQ-C30 and/or Disease Symptoms Domain of the EORTC QLQ-MY20	Baseline up to approximately 2 years
Serum Concentration of Cevostamab at Specified Timepoints	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.
Percentage of Participants with ADAs Against Cevostamab During the Study	Up to approximately 2 years
Cytokine Release Syndrome (CRS) Following Administration of Tocilizumab	Baseline up to approximately 2 years
Relationship Between Serum Concentration of Cevostamab and Cytokine Release	Baseline up to approximately 2 years
Relationship Between Serum Concentration of Cevostamab and T Cell Number	Baseline up to approximately 2 years
Relationship Between Serum Concentration of Cevostamab and T-cell Activation State	Baseline up to approximately 2 years
ORR as Determined by the Independent Review Committee (IRC)	Baseline up to approximately 2 years

Other Outcome Measures

Outcome Measure	Time Frame
Minimal Residual Disease (MRD) Negative Rate	Baseline up to approximately 2 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2022
• Primary Completion (Estimated): February 26, 2027
• Study Completion (Estimated): February 26, 2027

Study Registration Dates

• First Submitted: August 24, 2022
• First Submitted That Met QC Criteria: September 8, 2022
• First Posted (Actual): September 10, 2022

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; tocilizumab
• Other Study ID Numbers: CO43476; 2021-006816-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No