Multiple Myeloma
Conditions
Brief 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.
Detailed 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.
Interventions
DRUGCevostamab
Substudy 2: Cevostamab will be administered intravenously (IV) on a 28-day cycle, up to a total of 13 cycles. Substudy 4: Cevostamab will be administered by IV on a 21-day cycle, up to a total of 17 cycles.
DRUGLenalidomide
Lenalidomide will be administered PO on days 1-21 of a 28-day cycle.
DRUGTocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
DRUGIberdomide
Iberdomide will be administered PO on days 1-14 of a 21-day cycle.
DRUGDexamethasone
Dexamethasone will be administered on Days 2 and 8 of Cycles 1-3.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Stage 1: Percentage of Participants with Adverse Events (AEs) | Baseline up to approximately 5 years |
| Stage 2: Objective Response Rate (ORR) | Baseline up to approximately 5 years |
| Stage 2: Complete Response (CR) or Stringent Complete Response (sCR) Rate | Baseline up to approximately 5 years |
| Stage 2: Rate of Very Good Partial Response (VGPR) or Better | Baseline up to approximately 5 years |
| Stage 2: Progression-free Survival (PFS) | Baseline up to approximately 5 years |
| Stage 2: Overall Survival (OS) | Baseline up to approximately 5 years |
Secondary
| Measure | Time frame |
|---|---|
| Stage 1: Conversion to a Better Response | Baseline up to approximately 5 years |
| Stage 1: PFS | Baseline up to approximately 5 years |
| Stages 1 and 2: Duration of Response (DOR) | Baseline up to approximately 5 years |
| Stage 1: OS | Baseline up to approximately 5 years |
| Stages 1 and 2: Minimal Residual Disease (MRD) Negativity Rate | Baseline up to approximately 5 years |
| Stage 1: ORR | Baseline up to approximately 5 years |
| Stage 1: CR or sCR Rate | Baseline up to approximately 5 years |
| Stage 1: Rate of VGPR or Better | Baseline up to approximately 5 years |
| Stage 2: Stage 1: Percentage of Participants with AEs | Baseline up to approximately 5 years |
| Stages 1 and 2: Time to First Response (for Participants who Achieve a Response of PR or Better) | Baseline up to approximately 5 years |
| Stages 1 and 2: Time to Best Response (for Participants who Achieve a Response of PR or Better) | Baseline up to approximately 5 years |
| Stages 1 and 2: Maximum Concentration Observed (Cmax) | Baseline up to approximately 5 years |
| Stages 1 and 2: Minimum Concentration under Steady-State Conditions within a Dosing Interval (Cmin) | Baseline up to approximately 5 years |
| Stages 1 and 2: Time to Maximum Concentration (Tmax) | Baseline up to approximately 5 years |
| Stages 1 and 2: Area under the Concentration-Time Curve (AUC) | Baseline up to approximately 5 years |
| Stages 1 and 2: Total Clearance of Drug (CL) | Baseline up to approximately 5 years |
| Stages 1 and 2: Volume of Distribution at Steady State | Baseline up to approximately 5 years |
| Stages 1 and 2: Terminal half-life | Baseline up to approximately 5 years |
Countries
Australia, France, Germany, Poland, South Korea, Spain
Contacts
CONTACTReference Study ID Number: CO43923 https://forpatients.roche.com/
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed