A Study Evaluating the Safety and Efficacy of Multiple Treatments in Participants With Multiple Myeloma

Last updated: March 21, 2025
Sponsor: Hoffmann-La Roche
Overall Status: Active - Recruiting

Phase

1/2

Condition

Multiple Myeloma

Cancer/tumors

Platelet Disorders

Treatment

Cevostamab

RO7296682

Dexamethasone

Clinical Study ID

NCT05583617
CO43923
2021-005918-34
2023-504484-16-00
  • Ages > 18
  • All Genders

Study Summary

CO43923 is a platform study that will evaluate the safety, efficacy, and pharmacokinetics (PK) of multiple treatment combinations, as monotherapy or in combination, in participants with multiple myeloma (MM). The study is designed with the flexibility to open new treatment substudies as new treatments become available. Information regarding the opened substudies are found below.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Diagnosed with MM per International Myeloma Working Group (IMWG) criteria

  • Eastern Cooperative Oncology Group Performance Status of 0, or 1, or 2

  • Resolution of AEs from prior anti-cancer therapy to Grade <=1

  • Agreement to undergo scheduled assessments and procedures

Additional Inclusion Criteria for SS2:

  • Completion of planned induction therapy and achievement of at least a partialresponse (PR)

  • Autologous Stem Cell Transplant (SCT) within 100 days prior to first study treatmentand the absence of progressive disease

  • Cytogenetic high-risk features at diagnosis

  • Treatment with any investigational medicinal products, systemic cancer therapies,immunotherapies received previously in CO43923 (any arms) within 5 half-lives or 3weeks whichever is the shortest

  • Agreement to comply with all local requirements of the lenalidomide riskminimization plan, which includes the global pregnancy prevention program

  • For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception

  • For male participants: agreement to remain abstinent (refrain from heterosexualintercourse) or use a condom even if they have had a prior vasectomy, and agreementto refrain from donating sperm

Additional Inclusion Criteria for SS4:

  • Previously exposed to at least a PI, an IMiD, and an anti-CD38 antibody for thetreatment of R/R MM for whom no suitable SOC therapy options are available

Exclusion

Exclusion Criteria:

  • Inability to comply with protocol-mandated hospitalization and procedures

  • History of confirmed progressive multifocal leukoencephalopathy

  • History of other malignancy within 2 years prior to screening

  • Current or past history of central nervous system (CNS) disease

  • Significant cardiovascular disease that may limit a participant's ability toadequately respond to a CRS event

  • Symptomatic active pulmonary disease or requiring supplemental oxygen

  • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infectionat study enrollment, or any major episode of infection requiring treatment with IVantibiotics where the last dose of IV antibiotics was given within 14 days prior tofirst study treatment

  • Known or suspected chronic active Epstein-Barr virus (EBV) infection

  • 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 HIV seropositivity

  • Administration of a live, attenuated vaccine within 4 weeks prior to initiation ofstudy treatment or anticipation that such a live, attenuated vaccine will berequired during the study

  • Any medical condition or abnormality in clinical laboratory tests that, in theinvestigator's judgment, precludes the participant's safe participation in andcompletion of the study, or which could affect compliance with the protocol orinterpretation of results

Additional Exclusion Criteria for SS2:

  • Hypersensitivity reactions to lenalidomide or other immunomodulatory drugs

  • Harbor lesions at proximity of vital organs that may develop suddendecompensation/deterioration in the setting of a tumor flare

  • Prior treatment with any investigational medicinal product, systemic cancer therapy,or immunotherapies in any arm of study CO43923 within 5 half-lives or 3 weeks,whichever is shorter

  • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episodeof infection requiring treatment with IV antimicrobials where the last dose of IVantimicrobial was given within 14 days prior to first study treatment

  • History of erythema multiforme, Grade >=3 rash, or blistering following priortreatment with immunomodulatory derivatives

  • Pregnant or breastfeeding, or intending to become pregnant during the study orwithin 5 months after the final dose of study treatment Exlcusion CriteriaApplicable to SS2 and SS4

  • History of autoimmune disease

  • Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activationsyndrome (MAS)

  • History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)

  • Received a cumulative dose of corticosteroids equivalent to >=140 mg of prednisonewithin the 14-day period before the first dose of the study drug (does not includepretreatment medication)

  • Active symptomatic COVID-19 infection at study enrollment or requiring treatmentwith IV antiviral where the last dose of IV antiviral treatment was given within 14days prior to first study treatment. Participants with active COVID-19 infectionmust have clinical recovery and two negative antigen tests at least 24 hours apartprior to first study treatment.

  • Positive and quantifiable EBV PCR or CMV PCR prior to first study treatment

Additional Exclusion Criteria for SS4:

  • Treatment with any investigational medicinal products, systemic cancer therapies,immunotherapies within 5 half-lives or 12 weeks before starting pre-phase

  • History of anaphylaxis or hypersensitivity, including >=Grade 3 rash, during priortreatment with IMiDs, dexamethasone, any CELMoDs, or the excipients contained in theformulations

  • Known anaphylaxis, allergies, hypersensitivity, or intolerance to boron or mannitol,hyaluronidase, sorbitol, corticosteroids, monoclonal antibodies (or recombinantantibody-related fusion proteins), or human proteins, CRBN modulating agents ortheir excipients, or known sensitivity to mammalian-derived products

  • Administration of strong CYP3A modulators; administration of proton-pump inhibitorswithin 2 weeks of starting study treatment

  • Uncontrolled hypertension or uncontrolled diabetes within 14 days prior toenrollment

  • Concurrent administration of a strong inhibitor, modulator or inducer of cytochromeP450 (CYP3A4/5) (including within 14 days of initiating study treatment)

  • History of malignancies, other than MM, unless the subject has been free of thedisease for >=5 years

  • Peripheral neuropathy >Grade 2

  • Prior treatment with cevostamab or another agent targeting FcRH5 or iberdomide

  • Pregnant or breastfeeding, or intending to become pregnant during the study orwithin 5 months after the final dose of study treatment

  • History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug rash witheosinophilia and systemic symptoms

  • Treatment with systemic immunosuppressive medications

  • Prior treatment with CAR T-cell therapy (autologous or allogeneic) within 12 weeksbefore starting pre-phase

  • Autologous SCT within 100 days prior to starting pre-phase

  • Prior allogeneic SCT

  • Plasmacytoma in proximity of vital organs that may develop suddendecompensation/deterioration in the setting of a tumor flare

Study Design

Total Participants: 200
Treatment Group(s): 6
Primary Treatment: Cevostamab
Phase: 1/2
Study Start date:
November 14, 2023
Estimated Completion Date:
March 31, 2030

Study Description

Cevos + Len substudy(SS) 2 (DIRAC):

This substudy will explore the combination of cevostamab and lenalidomide as post-transplant maintenance therapy in participants with MM with high-risk cytogenetic features who experienced at least a partial response (PR) after induction.

Cevostamab + Iberdomide SS4 (CHAWLA):

This substudy will evaluate the safety, tolerability, PK, and pharmacodynamics of the combination of cevostamab and iberdomide in participants with R/R MM who have received at least three prior lines of therapy, including a PI, an IMiD, and an anti-CD38 monoclonal antibody.

Connect with a study center

  • Prince of Wales Hospital

    Randwick, New South Wales 2031
    Australia

    Active - Recruiting

  • Prince of Wales Hospital; Haematology

    Randwick, New South Wales 2031
    Australia

    Active - Recruiting

  • St Vincent's Hospital Melbourne

    Fitzroy, Victoria 3065
    Australia

    Active - Recruiting

  • CHU Lyon Sud - Service Hématologie

    Pierre Benite, 69310
    France

    Site Not Available

  • Hopital Bretonneau

    TOURS Cedex, 37044
    France

    Active - Recruiting

  • Hopital Bretonneau; Hematologie Therapie Cellulaire

    TOURS Cedex, 37044
    France

    Active - Recruiting

  • IUCT Oncopole

    Toulouse, 31059
    France

    Active - Recruiting

  • IUCT Oncopole; Hematologie

    Toulouse, 31059
    France

    Active - Recruiting

  • IGR

    Villejuif, 94800
    France

    Active - Recruiting

  • Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II

    Hamburg, 20246
    Germany

    Active - Recruiting

  • Universitätsklinikum Leipzig - Klinik und Poliklinik für Hämatologie

    Leipzig, 04103
    Germany

    Active - Recruiting

  • Samsung Medical Center

    Seoul, 06351
    Korea, Republic of

    Active - Recruiting

  • Severance Hospital, Yonsei University Health System

    Seoul, 03722
    Korea, Republic of

    Active - Recruiting

  • Uniwersyteckie Centrum Kliniczne

    Gda?sk, 80-214
    Poland

    Active - Recruiting

  • Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii

    Gda?sk, 80-214
    Poland

    Active - Recruiting

  • Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii

    Gdansk, 80-952
    Poland

    Site Not Available

  • Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie

    Olsztyn, 10-228
    Poland

    Active - Recruiting

  • Uniwersytecki Szpital Kliniczny w Poznaniu

    Pozna?, 60-569
    Poland

    Active - Recruiting

  • Uniwersytecki Szpital Kliniczny w Poznaniu; Oddzial Hematologii i Transplantacji Szpiku

    Pozna?, 60-569
    Poland

    Active - Recruiting

  • Hospital Universitari Germans Trias i Pujol

    Badalona, Barcelona 08915
    Spain

    Active - Recruiting

  • Hospital Universitari Germans Trias i Pujol; Servicio de Hematologia

    Badalona, Barcelona 08915
    Spain

    Active - Recruiting

  • Fundacion Jimenez Diaz

    Madrid, 28040
    Spain

    Active - Recruiting

  • Fundacion Jimenez Diaz; Servicio de Hematologia

    Madrid, 28040
    Spain

    Active - Recruiting

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010
    Spain

    Active - Recruiting

  • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

    Valencia, 46010
    Spain

    Active - Recruiting

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