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

Multiple Myeloma Clinical Trial

— PLYCOM  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05583617
• Other study ID #: CO43923
• Secondary ID: 2021-005918-3420
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 14, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: CO43923 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2026
• Est. primary completion date: March 16, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• 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.
• Lenalidomide
Lenalidomide will be administered PO on days 1-21 of a 28-day cycle.
• Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
• Iberdomide
Iberdomide will be administered PO on days 1-14 of a 21-day cycle.
• Dexamethasone
Dexamethasone will be administered on Days 2 and 8 of Cycles 1-3.

Locations

Country	Name	City	State
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Prince of Wales Hospital; Haematology	Randwick	New South Wales
France	CHU Lyon Sud - Service Hématologie	Pierre Benite
France	IUCT Oncopole; Hematologie	Toulouse
France	Hopital Bretonneau; Hematologie Therapie Cellulaire	TOURS Cedex
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Poland	Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii	Gda?sk
Poland	Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu; Oddzial Hematologii i Transplantacji Szpiku	Pozna?
Spain	Fundacion Jimenez Diaz; Servicio de Hematologia	Madrid
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Australia,  France,  Korea, Republic of,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stage 1: Percentage of Participants with Adverse Events (AEs)		Baseline up to approximately 5 years
Primary	Stage 2: Objective Response Rate (ORR)		Baseline up to approximately 5 years
Primary	Stage 2: Complete Response (CR) or Stringent Complete Response (sCR) Rate		Baseline up to approximately 5 years
Primary	Stage 2: Rate of Very Good Partial Response (VGPR) or Better		Baseline up to approximately 5 years
Primary	Stage 2: Progression-free Survival (PFS)		Baseline up to approximately 5 years
Primary	Stage 2: Overall Survival (OS)		Baseline up to approximately 5 years
Secondary	Stage 1: Conversion to a Better Response		Baseline up to approximately 5 years
Secondary	Stage 1: PFS		Baseline up to approximately 5 years
Secondary	Stages 1 and 2: Duration of Response (DOR)		Baseline up to approximately 5 years
Secondary	Stage 1: OS		Baseline up to approximately 5 years
Secondary	Stages 1 and 2: Minimal Residual Disease (MRD) Negativity Rate		Baseline up to approximately 5 years
Secondary	Stage 1: ORR		Baseline up to approximately 5 years
Secondary	Stage 1: CR or sCR Rate		Baseline up to approximately 5 years
Secondary	Stage 1: Rate of VGPR or Better		Baseline up to approximately 5 years
Secondary	Stage 2: Stage 1: Percentage of Participants with AEs		Baseline up to approximately 5 years
Secondary	Stages 1 and 2: Time to First Response (for Participants who Achieve a Response of PR or Better)		Baseline up to approximately 5 years
Secondary	Stages 1 and 2: Time to Best Response (for Participants who Achieve a Response of PR or Better)		Baseline up to approximately 5 years
Secondary	Stages 1 and 2: Maximum Concentration Observed (Cmax)		Baseline up to approximately 5 years
Secondary	Stages 1 and 2: Minimum Concentration under Steady-State Conditions within a Dosing Interval (Cmin)		Baseline up to approximately 5 years
Secondary	Stages 1 and 2: Time to Maximum Concentration (Tmax)		Baseline up to approximately 5 years
Secondary	Stages 1 and 2: Area under the Concentration-Time Curve (AUC)		Baseline up to approximately 5 years
Secondary	Stages 1 and 2: Total Clearance of Drug (CL)		Baseline up to approximately 5 years
Secondary	Stages 1 and 2: Volume of Distribution at Steady State		Baseline up to approximately 5 years
Secondary	Stages 1 and 2: Terminal half-life		Baseline up to approximately 5 years