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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05583617




Registration number
NCT05583617
Ethics application status
Date submitted
14/10/2022
Date registered
18/10/2022

Titles & IDs
Public title
A Study Evaluating the Safety and Efficacy of Multiple Treatments in Participants With Multiple Myeloma
Scientific title
A Platform Study Evaluating the Safety and Efficacy of Multiple Treatments in Patients With Multiple Myeloma
Secondary ID [1] 0 0
2021-005918-34
Secondary ID [2] 0 0
CO43923
Universal Trial Number (UTN)
Trial acronym
PLYCOM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cevostamab
Treatment: Drugs - Lenalidomide
Treatment: Drugs - Tocilizumab
Treatment: Drugs - Iberdomide
Treatment: Drugs - Dexamethasone

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.

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.


Treatment: Drugs: Cevostamab
Substudy 2: Cevostamab will be administered intravenously (IV) on a 28-day cycle, up to a total of 13 cycles.

Substudies 3 and 4: Cevostamab will be administered by IV on a 21-day cycle, up to a total of 17 cycles.

Treatment: Drugs: Lenalidomide
Lenalidomide will be administered PO on days 1-21 of a 28-day cycle.

Treatment: Drugs: Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.

Treatment: Drugs: Iberdomide
Iberdomide will be administered PO on days 1-14 of a 21-day cycle.

Treatment: Drugs: Dexamethasone
Dexamethasone will be administered on Days 2 and 8 of Cycles 1-3.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Stage 1: Percentage of Participants with Adverse Events (AEs)
Timepoint [1] 0 0
Baseline up to approximately 5 years
Primary outcome [2] 0 0
Stage 2: Objective Response Rate (ORR)
Timepoint [2] 0 0
Baseline up to approximately 5 years
Primary outcome [3] 0 0
Stage 2: Complete Response (CR) or Stringent Complete Response (sCR) Rate
Timepoint [3] 0 0
Baseline up to approximately 5 years
Primary outcome [4] 0 0
Stage 2: Rate of Very Good Partial Response (VGPR) or Better
Timepoint [4] 0 0
Baseline up to approximately 5 years
Primary outcome [5] 0 0
Stage 2: Progression-free Survival (PFS)
Timepoint [5] 0 0
Baseline up to approximately 5 years
Primary outcome [6] 0 0
Stage 2: Overall Survival (OS)
Timepoint [6] 0 0
Baseline up to approximately 5 years
Secondary outcome [1] 0 0
Stage 1: Conversion to a Better Response
Timepoint [1] 0 0
Baseline up to approximately 5 years
Secondary outcome [2] 0 0
Stage 1: PFS
Timepoint [2] 0 0
Baseline up to approximately 5 years
Secondary outcome [3] 0 0
Stages 1 and 2: Duration of Response (DOR)
Timepoint [3] 0 0
Baseline up to approximately 5 years
Secondary outcome [4] 0 0
Stage 1: OS
Timepoint [4] 0 0
Baseline up to approximately 5 years
Secondary outcome [5] 0 0
Stages 1 and 2: Minimal Residual Disease (MRD) Negativity Rate
Timepoint [5] 0 0
Baseline up to approximately 5 years
Secondary outcome [6] 0 0
Stage 1: ORR
Timepoint [6] 0 0
Baseline up to approximately 5 years
Secondary outcome [7] 0 0
Stage 1: CR or sCR Rate
Timepoint [7] 0 0
Baseline up to approximately 5 years
Secondary outcome [8] 0 0
Stage 1: Rate of VGPR or Better
Timepoint [8] 0 0
Baseline up to approximately 5 years
Secondary outcome [9] 0 0
Stage 2: Stage 1: Percentage of Participants with AEs
Timepoint [9] 0 0
Baseline up to approximately 5 years
Secondary outcome [10] 0 0
Stages 1 and 2: Time to First Response (for Participants who Achieve a Response of PR or Better)
Timepoint [10] 0 0
Baseline up to approximately 5 years
Secondary outcome [11] 0 0
Stages 1 and 2: Time to Best Response (for Participants who Achieve a Response of PR or Better)
Timepoint [11] 0 0
Baseline up to approximately 5 years
Secondary outcome [12] 0 0
Stages 1 and 2: Maximum Concentration Observed (Cmax)
Timepoint [12] 0 0
Baseline up to approximately 5 years
Secondary outcome [13] 0 0
Stages 1 and 2: Minimum Concentration under Steady-State Conditions within a Dosing Interval (Cmin)
Timepoint [13] 0 0
Baseline up to approximately 5 years
Secondary outcome [14] 0 0
Stages 1 and 2: Time to Maximum Concentration (Tmax)
Timepoint [14] 0 0
Baseline up to approximately 5 years
Secondary outcome [15] 0 0
Stages 1 and 2: Area under the Concentration-Time Curve (AUC)
Timepoint [15] 0 0
Baseline up to approximately 5 years
Secondary outcome [16] 0 0
Stages 1 and 2: Total Clearance of Drug (CL)
Timepoint [16] 0 0
Baseline up to approximately 5 years
Secondary outcome [17] 0 0
Stages 1 and 2: Volume of Distribution at Steady State
Timepoint [17] 0 0
Baseline up to approximately 5 years
Secondary outcome [18] 0 0
Stages 1 and 2: Terminal half-life
Timepoint [18] 0 0
Baseline up to approximately 5 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 allergies, hypersensitivity, or intolerance to boron or mannitol, hyaluronidase, sorbitol, corticosteroids, monoclonal antibodies 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 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/11/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Prince of Wales Hospital; Haematology - Randwick
Recruitment hospital [2] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
France
State/province [1] 0 0
Pierre Benite
Country [2] 0 0
France
State/province [2] 0 0
Toulouse
Country [3] 0 0
France
State/province [3] 0 0
TOURS Cedex
Country [4] 0 0
Korea, Republic of
State/province [4] 0 0
Seoul
Country [5] 0 0
Poland
State/province [5] 0 0
Gda?sk
Country [6] 0 0
Poland
State/province [6] 0 0
Olsztyn
Country [7] 0 0
Poland
State/province [7] 0 0
Pozna?
Country [8] 0 0
Spain
State/province [8] 0 0
Barcelona
Country [9] 0 0
Spain
State/province [9] 0 0
Madrid
Country [10] 0 0
Spain
State/province [10] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: CO43923 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org/). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm)
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05583617