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Phase I / Phase II: Cevostamab in Multiple Myeloma (PLYCOM)

Clinical Trial Overview

Clinical Trial Overview

Recruiting

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

Objective

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.

Primary Endpoints

  • Stage 1: Percentage of Participants with Adverse Events (AEs)
  • Stage 2: Objective Response Rate (ORR)
  • Stage 2: Complete Response (CR) or Stringent Complete Response (sCR) Rate
  • Stage 2: Rate of Very Good Partial Response (VGPR) or Better
  • Stage 2: Progression-free Survival (PFS)
  • Stage 2: Overall Survival (OS)

Secondary Endpoints

  • Stage 1: Conversion to a Better Response
  • Stage 1: PFS
  • Stages 1 and 2: Duration of Response (DOR)
  • Stage 1: OS
  • Stages 1 and 2: Minimal Residual Disease (MRD) Negativity Rate
  • Stage 1: ORR
  • Stage 1: CR or sCR Rate
  • Stage 1: Rate of VGPR or Better
  • Stage 2: Stage 1: Percentage of Participants with AEs
  • Stages 1 and 2: Time to First Response (for Participants who Achieve a Response of PR or Better)
  • Stages 1 and 2: Time to Best Response (for Participants who Achieve a Response of PR or Better)
  • Stages 1 and 2: Maximum Concentration Observed (Cmax)
  • Stages 1 and 2: Minimum Concentration under Steady-State Conditions within a Dosing Interval (Cmin)
  • Stages 1 and 2: Time to Maximum Concentration (Tmax)
  • Stages 1 and 2: Area under the Concentration-Time Curve (AUC)
  • Stages 1 and 2: Total Clearance of Drug (CL)
  • Stages 1 and 2: Volume of Distribution at Steady State
  • Stages 1 and 2: Terminal half-life

Cevostamab

Other names: RG6160; RO7187797

Modality: anti-FcRH5/CD3 bispecific antibody

Disease/Condition: Multiple Myeloma


ADDITIONAL RESOURCES

Inclusion and Exclusion Criteria

Inclusion and Exclusion Criteria

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 partial response (PR)
  • Autologous Stem Cell Transplant (SCT) within 100 days prior to first study treatment and 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 3 weeks whichever is the shortest
  • Agreement to comply with all local requirements of the lenalidomide risk minimization 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 heterosexual intercourse) or use a condom even if they have had a prior vasectomy, and agreement to refrain from donating sperm

Additional Inclusion Criteria for SS4:

  • Previously exposed to at least a PI, an IMiD, and an anti-CD38 antibody for the treatment of R/R MM for whom no suitable SOC therapy options are available
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 to adequately respond to a 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 antibiotics where the last dose of IV antibiotics was given within 14 days prior to first 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 of study treatment or anticipation that such a live, attenuated vaccine will be required during the study
  • 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

Additional Exclusion Criteria for SS2:

  • Hypersensitivity reactions to lenalidomide or other immunomodulatory drugs
  • Harbor lesions at proximity of vital organs that may develop sudden decompensation/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 episode of infection requiring treatment with IV antimicrobials where the last dose of IV antimicrobial was given within 14 days prior to first study treatment
  • History of erythema multiforme, Grade >=3 rash, or blistering following prior treatment with immunomodulatory derivatives
  • Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of study treatment Exlcusion Criteria Applicable to SS2 and SS4
  • History of autoimmune disease
  • Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (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 prednisone within the 14-day period before the first dose of the study drug (does not include pretreatment medication)
  • 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 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 prior treatment with IMiDs, dexamethasone, any CELMoDs, or the excipients contained in the formulations
  • Known anaphylaxis, allergies, hypersensitivity, or intolerance to boron or mannitol, hyaluronidase, sorbitol, corticosteroids, monoclonal antibodies (or recombinant antibody-related fusion proteins), or human proteins, CRBN modulating agents or their excipients, or known sensitivity to mammalian-derived products
  • Administration of strong CYP3A modulators; administration of proton-pump inhibitors within 2 weeks of starting study treatment
  • Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment
  • Concurrent administration of a strong inhibitor, modulator or inducer of cytochrome P450 (CYP3A4/5) (including within 14 days of initiating study treatment)
  • History of malignancies, other than MM, unless the subject has been free of the disease 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 or within 5 months after the final dose of study treatment
  • History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug rash with eosinophilia and systemic symptoms
  • Treatment with systemic immunosuppressive medications
  • Prior treatment with CAR T-cell therapy (autologous or allogeneic) within 12 weeks before 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 sudden decompensation/deterioration in the setting of a tumor flare
Study Site Locations

0 Results

    Enrollment and Resources

    Enrollment & Resources

    Enrollment

    For more information on eligibility criteria, view the study or reach out to our team.

    Call icon

    Phone

    1-888-662-6728
    (US and Canada)

    Resources

    ClinicalTrials.gov

    Learn more about this trial (NCT05583617) on ClinicalTrials.gov.

    Patient Resources

    Genentech offers a place for patients, relatives, and caregivers to learn more about clinical trials.

    Information is consistent with ClinicalTrials.gov as of October 06, 2026. Products under investigation have not been approved for use outside of the clinical trial setting. This information is presented only for the purposes of providing an overview of clinical trials and should not be construed as a recommendation for use of any product for unapproved purposes.

    Looking for more information?

    Reach out to a Genentech Medical Science Liaison near you, or connect with the contact center.

    Call the Trial Information Support Team: 1-888-662-6728 Hours: Monday-Friday, 5am-5pm PT

    • AD
      Alzheimer's disease

    • ABC
      advanced breast cancer

    • bADLs
      Basic activities of daily living

    • ISLT
      International Shopping List Test

    • MCI
      Mild cognitive impairment

    • CV
      coefficient of variation

    • HEX
      cell hexagonality

    • PDS
      Port Delivery System

    • Q24W
      once every 24 weeks

    • BMI
      Body mass index

    • HbA1c
      hemoglobin A1C

    • HOMA-IR
      Homeostasis Model Assessment of Insulin Resistance

    • NLM
      National Library of Medicine

    • QUICKI
      Quantitative Insulin Sensitivity Check Index

    • SGLT-2
      sodium-glucose cotransporter-2

    • SMBG
      Self-Monitored Blood Glucose

    • T1DM
      Type 1 Diabetes Mellitus

    • T2DM
      Type 2 diabetes mellitus

    • AE
      adverse events

    • AESI
      Adverse Events of Special Interest

    • MDD
      major depressive disorder

    • PHQ-9
      Patient Health Questionnaire-9

    • SAE
      serious adverse events

    • ABR
      Annualized Bleed Rate

    • CBR
      clinical benefit rate

    • CDK4/6i
      cyclin-dependent kinase 4 and 6 inhibitor

    • CNS
      central nervous system

    • CR
      complete response

    • DoR
      duration of response

    • ER
      estrogen receptor

    • HER2
      human epidermal growth factor receptor 2

    • HER2-
      human epidermal growth factor receptor 2-negative

    • HR
      hormone receptor

    • HR+
      hormone receptor-positive

    • mut
      mutated

    • NIS
      non-interventional study

    • ORR
      objective response rate

    • OS
      overall survival

    • PFS
      progression-free-survival

    • PIK3CA
      phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha

    • PIK3CAm
      PIK3CA-mutated

    • PK
      pharmacokinetics

    • PROs
      patient-reported outcomes

    • SD
      stable disease

    • SoC
      standard of care

    • VWD
      von Willebrand disease

    • WHO
      World Health Organization

    • T2D
      Type 2 diabetes

    • T1D
      Type 1 Diabetes

    • ADA
      anti-drug antibody

    • DXA
      Dual-energy X-ray Absorptiometry

    • ASCVD
      atherosclerotic cardiovascular disease

    • FGF21
      fibroblast growth factor 21

    • SHTG
      severe hypertriglyceridemia

    • TG
      triglycerides

    • MASH
      metabolic dysfunction-associated steatohepatitis

    • NAFLD
      non-alcoholic fatty liver disease

    • NAS
      NAFLD Activity Score

    • NASH
      nonalcoholic steatohepatitis

    • pmMS
      partial modified Mayo

    • CD
      Crohn's disease

    • CMV
      cytomegalovirus

    • HIV
      human immunodeficiency virus

    • HBV
      Hepatitis B

    • HCV
      Hepatitis C

    • TB
      tuberculosis

    • UC
      ulcerative colitis

    • TL1A
      tumor necrosis factor-like ligand 1A

    • mMS
      modified Mayo Score

    • APS
      average daily abdominal pain scores in the past week

    • CDAI
      Crohn’s Disease Activity Index

    • IBDQ
      Inflammatory Bowel Disease Questionnaire

    • SF
      stool frequency subscore

    • PBO
      Placebo

    • EASI
      Eczema Area and Severity Index

    • IGA
      Investigator Global Assessment

    • NRS
      Numerical Rating Scale

    • IM
      intramuscular

    • IL
      intralesional

    • PDE-4
      Phosphodiesterase-4

    • ACE
      angiotensin-converting enzyme

    • ARBs
      angiotensin II receptor blockers

    • ASO
      Antisense Oligonucleotide

    • CKD-EPI
      Chronic Kidney Disease Epidemiology Collaboration

    • eGFR
      Estimated Glomerular Filtration Rate

    • FACIT-F
      Functional Assessment of Chronic Illness Therapy-Fatigue subscale

    • g/day
      gram per day

    • g/g
      gram per gram

    • GIP
      Glucose-dependent Insulinotropic Polypeptide

    • GLP-1
      Glucagon-like Peptide-1

    • IgAN
      IgA nephropathy

    • mg/day
      milligrams per day

    • TEAEs
      Treatment-Emergent Adverse Events

    • UPCR
      Urine Protein-to-Creatinine Ratio

    • AEs
      Adverse events

    • ALT
      Alanine aminotransferase

    • AST
      Aspartate aminotransferase

    • C-SSRS
      Columbia-Suicide Severity Rating Scale

    • DMT
      Disease-modifying therapy

    • ECG
      Electrocardiogram

    • EDSS
      Expanded Disability Status Scale

    • Gd
      Gadolinium

    • IPMSSG
      International Pediatric Multiple Sclerosis Study Group

    • MRI
      Magnetic resonance imaging

    • MS
      Multiple sclerosis

    • PD
      Pharmacodynamic

    • PPMS
      Primary progressive multiple sclerosis

    • RMS
      Relapsing multiple sclerosis

    • SI
      Suicidal ideation

    • SPMS
      Secondary progressive multiple sclerosis

    • CYP3A4
      cytochrome-p450-3a4

    • ADAS-Cog-13
      Alzheimer's Disease Assessment Scale-Cognition 13

    • ADAs
      Anti-drug antibodies

    • ADCS-ADL
      Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory

    • CDR-GS
      Clinical Dementia Rating, Global Score

    • CDR-SB
      Clinical Dementia Rating, Sum of Boxes

    • CSF
      Cerebrospinal fluid

    • GFAP
      Glial fibrillar acidic protein

    • iADRS
      Integrated Alzheimer's Disease Rating Scale

    • MMSE
      Mini-Mental State Examination

    • PET
      Positron emission tomography

    • RBANS DMI
      Repeatable Battery for the Assessment of Neuropsychological Status Delayed Memory Index

    • EORTC QLQ-C30
      European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire

    • PRO-CTCAE
      Patient-Reported Outcomes Common Terminology Criteria for Adverse Events

    • TTCD
      Time to Confirmed Deterioration

    • AJCC
      American Joint Committee on Cancer Staging System

    • ECOG
      Eastern Cooperative Oncology Group

    • FFPE
      formalin-fixed, paraffin-embedded

    • RECIST
      Response Evaluation Criteria in Solid Tumors

    • NSCLC
      non-small cell lung cancer

    • BICR
      blinded independent central review

    • CD137
      Cluster of Differentiation 137

    • EORTC QLQ-LC13
      European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Supplemental Lung Cancer Module

    • KRAS G12C
      Kirsten rat sarcoma viral oncogene homolog G12C

    • PD-L1
      Programmed death-ligand 1

    • RAS
      RAt Sarcoma

    • RT
      Radiation therapy

    • DOCR
      duration of complete response

    • DFS
      disease-free survival

    • EFSeff
      event-free survival efficacy causes

    • FACT-Lym LymS
      lymphoma subscale within the functional assessment of cancer therapy-Lymphoma questionnaire

    • IPI
      international prognostic index

    • IRF
      Independent Review Facility

    • Pola-R-CHP
      polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone

    • LBCL
      large B-cell lymphoma

    • PROMIS-29
      Patient-Reported Outcomes Measurement Information System-29

    • ESR1nmd
      ESR1 no-mutation-detected

    • IV
      intravenous

    • II
      2

    • ECD
      endothelial cell density

    • III
      3

    • SC
      Subcutaneous

    +