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

NCT05583617 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: CO439232021-005918-342023-504484-16-00
• Study Type: interventional
• Target: 200
• Locations: 6 countries
• Sites: 16

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (18)

• 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

Study Arms (2)

Substudy 2: Dose Escalation and Expansion

EXPERIMENTAL

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

Substudy 4: Dose Escalation and Expansion

EXPERIMENTAL

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

Interventions

Tocilizumab DRUG

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

Substudy 2: Dose Escalation and Expansion; Substudy 4: Dose Escalation and Expansion

Iberdomide DRUG

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

Substudy 4: Dose Escalation and Expansion

Dexamethasone DRUG

Dexamethasone will be administered on Days 2 and 8 of Cycles 1-3.

Substudy 4: Dose Escalation and Expansion

Cevostamab DRUG

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.

Substudy 2: Dose Escalation and Expansion; Substudy 4: Dose Escalation and Expansion

Lenalidomide DRUG

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

Substudy 2: Dose Escalation and Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (16)

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

RECRUITING

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

RECRUITING

CHU Lyon Sud - Service Hématologie

Pierre-Bénite, 69310, France

RECRUITING

IUCT Oncopole

Toulouse, 31059, France

RECRUITING

Hopital Bretonneau

Tours, 37044, France

RECRUITING

IGR

Villejuif, 94800, France

WITHDRAWN

Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II

Hamburg, 20246, Germany

RECRUITING

Universitätsklinikum Leipzig - Klinik und Poliklinik für Hämatologie

Leipzig, 04103, Germany

RECRUITING

Uniwersyteckie Centrum Kliniczne

Gda?sk, 80-214, Poland

RECRUITING

Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie

Olsztyn, 10-228, Poland

RECRUITING

Uniwersytecki Szpital Kliniczny w Poznaniu

Późna, 60-569, Poland

WITHDRAWN

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08915, Spain

RECRUITING

Fundacion Jimenez Diaz

Madrid, 28040, Spain

RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; tocilizumab; iberdomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: CO43923 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2022
• First Posted: October 18, 2022
• Study Start: November 14, 2023
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

AU (2); PL (3); FR (4); ES (3); KR (2); DE (2)