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

PHASE1PHASE2RECRUITING

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.

Study details:

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.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Diagnosed with MM per International Myeloma Working Group (IMWG) criteria
  2. Eastern Cooperative Oncology Group Performance Status of 0, or 1, or 2
  3. Resolution of AEs from prior anti-cancer therapy to Grade <=1
  4. Agreement to undergo scheduled assessments and procedures
  5. Completion of planned induction therapy and achievement of at least a partial response (PR)
  6. Autologous Stem Cell Transplant (SCT) within 100 days prior to first study treatment and the absence of progressive disease
  7. Cytogenetic high-risk features at diagnosis
  8. 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
  9. Agreement to comply with all local requirements of the lenalidomide risk minimization plan, which includes the global pregnancy prevention program
  10. For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception
  11. 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
  12. 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

  1. Inability to comply with protocol-mandated hospitalization and procedures
  2. History of confirmed progressive multifocal leukoencephalopathy
  3. History of other malignancy within 2 years prior to screening
  4. Current or past history of central nervous system (CNS) disease
  5. Significant cardiovascular disease that may limit a participant's ability to adequately respond to a CRS event
  6. Symptomatic active pulmonary disease or requiring supplemental oxygen
  7. 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
  8. Known or suspected chronic active Epstein-Barr virus (EBV) infection
  9. Positive serologic or PCR test results for acute or chronic hepatitis B virus (HBV) infection
  10. Acute or chronic hepatitis C virus (HCV) infection
  11. Known history of HIV seropositivity
  12. 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
  13. 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
  14. Hypersensitivity reactions to lenalidomide or other immunomodulatory drugs
  15. Harbor lesions at proximity of vital organs that may develop sudden decompensation/deterioration in the setting of a tumor flare
  16. 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
  17. 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
  18. History of erythema multiforme, Grade >=3 rash, or blistering following prior treatment with immunomodulatory derivatives
  19. Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of study treatment
  20. History of autoimmune disease
  21. Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
  22. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
  23. 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)
  24. 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.
  25. Positive and quantifiable EBV PCR or CMV PCR prior to first study treatment
  26. Treatment with any investigational medicinal products, systemic cancer therapies, immunotherapies within 5 half-lives or 12 weeks before starting pre-phase
  27. History of anaphylaxis or hypersensitivity, including >=Grade 3 rash, during prior treatment with IMiDs, dexamethasone, any CELMoDs, or the excipients contained in the formulations
  28. 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
  29. Administration of strong CYP3A modulators; administration of proton-pump inhibitors within 2 weeks of starting study treatment
  30. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment
  31. Concurrent administration of a strong inhibitor, modulator or inducer of cytochrome P450 (CYP3A4/5) (including within 14 days of initiating study treatment)
  32. History of malignancies, other than MM, unless the subject has been free of the disease for >=5 years
  33. Peripheral neuropathy >Grade 2
  34. Prior treatment with cevostamab or another agent targeting FcRH5 or iberdomide
  35. Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of study treatment
  36. History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug rash with eosinophilia and systemic symptoms
  37. Treatment with systemic immunosuppressive medications
  38. Prior treatment with CAR T-cell therapy (autologous or allogeneic) within 12 weeks before starting pre-phase
  39. Autologous SCT within 100 days prior to starting pre-phase
  40. Prior allogeneic SCT
  41. Plasmacytoma in proximity of vital organs that may develop sudden decompensation/deterioration in the setting of a tumor flare

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE1PHASE2

trial

Study ID

NCT05583617

Intervention or treatment

DRUG: Cevostamab

DRUG: Lenalidomide

DRUG: Tocilizumab

DRUG: Iberdomide

DRUG: Dexamethasone

Conditions

  • Multiple Myeloma

  • Condition: Multiple Myeloma

  • DRUG: Cevostamab and other drugs

  • Randwick, New South Wales, Australia and more

  • Sponsor: Hoffmann-La Roche

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Research sites nearby

Closest Location:

Prince of Wales Hospital

Select from list below to view details:

  • Prince of Wales Hospital

    Randwick, New South Wales, Australia

  • St Vincent's Hospital Melbourne

    Fitzroy, Victoria, Australia

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Who is running the clinical trial?

HR

Hoffmann-La Roche

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Substudy 2: Dose Escalation and Expansion
  • In the pre-phase, participants will receive 2 step-up doses and a target dose of cevostamab. The step-up dose will be given on Day(D)1 and D4. The target dose will be given on D8. Subsequently the target dose will be administered on D1 and D15 for cycles 1-6 and D1 of cycle 7 onwards. Each cycle is 28 days. Lenalidomide will be administered by mouth (PO) on a 28-day cycle.
  • During the dose expansion phase, cevostamab will be administered following the same dosing schedule as the dose escalation phase. The target dose will be determined after the escalation phase. Lenalidomide will be administered PO on a 28-day cycle.
  • Enrollment for Substudy 2 has closed.
Drug: Cevostamab, Drug: Lenalidomide, Drug: Tocilizumab
    EXPERIMENTAL: Substudy 4: Dose Escalation and Expansion
    • In the pre-phase, participants will receive 2 step-up doses and a target dose of cevostamab. The step-up dose will be given on D1 and D4. The target dose will be given on D8. Subsequently the target dose will be administered on D1 of each cycle, every 3 weeks (Q3W). Each cycle is 21 days. Iberdomide will be administered PO on a 21-day cycle.
    • During the dose expansion phase, cevostamab will be administered following the same dosing schedule as the dose escalation phase. The target dose will be determined after the escalation phase. Iberdomide will be administered PO on a 21-day cycle.
    Drug: Cevostamab, Drug: Tocilizumab, Drug: Iberdomide, Drug: Dexamethasone

      What is the study measuring?

      Primary Outcome

      MeasureDescriptionTime Frame
      Stage 1: Percentage of Participants with Adverse Events (AEs)Not SpecifiedBaseline up to approximately 5 years
      Stage 2: Objective Response Rate (ORR)Not SpecifiedBaseline up to approximately 5 years
      Stage 2: Complete Response (CR) or Stringent Complete Response (sCR) RateNot SpecifiedBaseline up to approximately 5 years
      Stage 2: Rate of Very Good Partial Response (VGPR) or BetterNot SpecifiedBaseline up to approximately 5 years
      Stage 2: Progression-free Survival (PFS)Not SpecifiedBaseline up to approximately 5 years
      Stage 2: Overall Survival (OS)Not SpecifiedBaseline up to approximately 5 years

      Secondary Outcome

      MeasureDescriptionTime Frame
      Stage 1: Conversion to a Better ResponseNot SpecifiedBaseline up to approximately 5 years
      Stage 1: PFSNot SpecifiedBaseline up to approximately 5 years
      Stages 1 and 2: Duration of Response (DOR)Not SpecifiedBaseline up to approximately 5 years
      Stage 1: OSNot SpecifiedBaseline up to approximately 5 years
      Stages 1 and 2: Minimal Residual Disease (MRD) Negativity RateNot SpecifiedBaseline up to approximately 5 years
      Stage 1: ORRNot SpecifiedBaseline up to approximately 5 years
      Stage 1: CR or sCR RateNot SpecifiedBaseline up to approximately 5 years
      Stage 1: Rate of VGPR or BetterNot SpecifiedBaseline up to approximately 5 years
      Stage 2: Stage 1: Percentage of Participants with AEsNot SpecifiedBaseline up to approximately 5 years
      Stages 1 and 2: Time to First Response (for Participants who Achieve a Response of PR or Better)Not SpecifiedBaseline up to approximately 5 years
      Stages 1 and 2: Time to Best Response (for Participants who Achieve a Response of PR or Better)Not SpecifiedBaseline up to approximately 5 years
      Stages 1 and 2: Maximum Concentration Observed (Cmax)Not SpecifiedBaseline up to approximately 5 years
      Stages 1 and 2: Minimum Concentration under Steady-State Conditions within a Dosing Interval (Cmin)Not SpecifiedBaseline up to approximately 5 years
      Stages 1 and 2: Time to Maximum Concentration (Tmax)Not SpecifiedBaseline up to approximately 5 years
      Stages 1 and 2: Area under the Concentration-Time Curve (AUC)Not SpecifiedBaseline up to approximately 5 years
      Stages 1 and 2: Total Clearance of Drug (CL)Not SpecifiedBaseline up to approximately 5 years
      Stages 1 and 2: Volume of Distribution at Steady StateNot SpecifiedBaseline up to approximately 5 years
      Stages 1 and 2: Terminal half-lifeNot SpecifiedBaseline up to approximately 5 years
      Are you running this trial?If you're a clinic or sponsor, you can claim this study.
      Claim this trial

      References

      Clinical Trials Gov: A Study Evaluating the Safety and Efficacy of Multiple Treatments in Participants With Multiple Myeloma

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