Back to resultsA Study Evaluating the Safety, Pharmacokinetics, and Activity of the Combination of Cevostamab and Elranatamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)
Primary Purpose
Relapsed or Refractory Multiple Myeloma
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Cevostamab
Elranatamab
Tocilizumab
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed or Refractory Multiple Myeloma
Eligibility Criteria
Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Diagnosis of R/R MM per IMWG criteria For female participants of childbearing potential: agreement to remain abstinent or use contraception For male participants: agreement to remain abstinent or use a condom Exclusion Criteria: Prior treatment with cevostamab or another agent targeting fragment crystallizable receptor-like 5 (FcRH5) Prior treatment with elranatamab Prior allogeneic stem cell transplantation (SCT) Absolute plasma cell count exceeding 500 per milliliter (mL) or 5% of the peripheral blood white cells Diagnosis of Waldenström macroglobulinemia or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome Participants with known history of amyloidosis History of autoimmune disease History of confirmed progressive multifocal leukoencephalopathy Peripheral motor polyneuropathy of prespecified grade Known or suspected chronic cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) infection History of hemophagocytic lymphohistiocytosis Acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection Human immunodeficiency virus (HIV) seropositivity History of central nervous system (CNS) myeloma disease Significant cardiovascular disease
Sites / Locations
- The Alfred HospitalRecruiting
- Sheba Medical Center - PPDSRecruiting
- The Catholic University of Korea - Seoul St. Mary's Hospital (Kangnam St. Mary's Hospital)Recruiting
- Seoul National University HospitalRecruiting
- Samsung Medical Center - PPDSRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Safety Lead-In Cohort
Dose Expansion Cohort
Arm Description
Participants will receive cevostamab, intravenously (IV), in combination with elranatamab, subcutaneously (SC), with step-up dosing of each drug in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first.
Participants will receive cevostamab, IV, in combination with elranatamab, SC, with step-up dosing of each drug in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first.
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events (AEs)
Adverse events will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0), and CRS will be graded based on the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading. Immune effector cell-associated neurotoxicity syndrome (ICANS) will be graded based on NCI CTCAE v5.0 and ASTCT Consensus Grading.
Secondary Outcome Measures
Objective Response Rate (ORR) as Determined by the Investigator per International Myeloma Working Group (IMWG) Criteria
Complete Response (CR)/ Stringent Complete Response (sCR) Rate as Determined by the Investigator per IMWG Criteria
Rate of Very Good Partial Response (VGPR) or Better, as Determined by the Investigator per IMWG Criteria
Progression-Free Survival as Determined by the Investigator per IMWG Criteria
Duration of Response (DOR) as Determined by the Investigator (for Participants who Achieve a Response of Partial Response (PR) or Better)
Time to First Response (for Participants who Achieve a Response of PR or Better)
Time to Best Response (for Participants who Achieve a Response of PR or Better)
Overall Survival (OS)
Serum Concentration of Cevostamab at Specified Timepoints
Serum Concentration of Elranatamab at Specified Timepoints
Number of Participants with Anti-Drug Antibody (ADA) Against Cevostamab
Number of Participants with ADA Against Elranatamab
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05927571
Brief Title
A Study Evaluating the Safety, Pharmacokinetics, and Activity of the Combination of Cevostamab and Elranatamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)
Official Title
An Open-Label, Multicenter, Phase Ib Trial Evaluating the Safety, Pharmacokinetics, and Activity of the Combination of Cevostamab and Elranatamab in Patients With Relapsed or Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 9, 2023 (Actual)
Primary Completion Date
July 31, 2026 (Anticipated)
Study Completion Date
July 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of the study is to evaluate safety and tolerability of the combination of cevostamab plus elranatamab and also determine the recommended Phase II dose (RP2D) for the study treatment. The study consists of a safety lead-in stage, and an expansion stage.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed or Refractory Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
110 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Safety Lead-In Cohort
Arm Type
Experimental
Arm Description
Participants will receive cevostamab, intravenously (IV), in combination with elranatamab, subcutaneously (SC), with step-up dosing of each drug in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first.
Arm Title
Dose Expansion Cohort
Arm Type
Experimental
Arm Description
Participants will receive cevostamab, IV, in combination with elranatamab, SC, with step-up dosing of each drug in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first.
Intervention Type
Drug
Intervention Name(s)
Cevostamab
Intervention Description
Cevostamab solution for infusion will be administered as IV as specified in each treatment arm.
Intervention Type
Drug
Intervention Name(s)
Elranatamab
Intervention Description
Elranatamab solution for injection will be administered SC as specified in each treatment arm.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Intervention Description
Tocilizumab will be used as rescue medication for participants who experience a cytokine release syndrome (CRS) event.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs)
Description
Adverse events will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0), and CRS will be graded based on the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading. Immune effector cell-associated neurotoxicity syndrome (ICANS) will be graded based on NCI CTCAE v5.0 and ASTCT Consensus Grading.
Time Frame
From signing of informed consent up to end of study (EOS) (approximately 36 months)
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR) as Determined by the Investigator per International Myeloma Working Group (IMWG) Criteria
Time Frame
Up to approximately 36 months
Title
Complete Response (CR)/ Stringent Complete Response (sCR) Rate as Determined by the Investigator per IMWG Criteria
Time Frame
Up to approximately 36 months
Title
Rate of Very Good Partial Response (VGPR) or Better, as Determined by the Investigator per IMWG Criteria
Time Frame
Up to approximately 36 months
Title
Progression-Free Survival as Determined by the Investigator per IMWG Criteria
Time Frame
Up to approximately 36 months
Title
Duration of Response (DOR) as Determined by the Investigator (for Participants who Achieve a Response of Partial Response (PR) or Better)
Time Frame
Up to approximately 36 months
Title
Time to First Response (for Participants who Achieve a Response of PR or Better)
Time Frame
Up to approximately 36 months
Title
Time to Best Response (for Participants who Achieve a Response of PR or Better)
Time Frame
Up to approximately 36 months
Title
Overall Survival (OS)
Time Frame
Up to approximately 36 months
Title
Serum Concentration of Cevostamab at Specified Timepoints
Time Frame
Up to approximately 36 months
Title
Serum Concentration of Elranatamab at Specified Timepoints
Time Frame
Up to approximately 36 months
Title
Number of Participants with Anti-Drug Antibody (ADA) Against Cevostamab
Time Frame
Up to approximately 36 months
Title
Number of Participants with ADA Against Elranatamab
Time Frame
Up to approximately 36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Diagnosis of R/R MM per IMWG criteria
For female participants of childbearing potential: agreement to remain abstinent or use contraception
For male participants: agreement to remain abstinent or use a condom
Exclusion Criteria:
Prior treatment with cevostamab or another agent targeting fragment crystallizable receptor-like 5 (FcRH5)
Prior treatment with elranatamab
Prior allogeneic stem cell transplantation (SCT)
Absolute plasma cell count exceeding 500 per milliliter (mL) or 5% of the peripheral blood white cells
Diagnosis of Waldenström macroglobulinemia or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome
Participants with known history of amyloidosis
History of autoimmune disease
History of confirmed progressive multifocal leukoencephalopathy
Peripheral motor polyneuropathy of prespecified grade
Known or suspected chronic cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) infection
History of hemophagocytic lymphohistiocytosis
Acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
Human immunodeficiency virus (HIV) seropositivity
History of central nervous system (CNS) myeloma disease
Significant cardiovascular disease
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
GO43979 https://forpatients.roche.com/
Phone
888-662-6728 (U.S. Only)
Email
global-roche-genentech-trials@gene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
The Alfred Hospital
City
Prahan
State/Province
Victoria
ZIP/Postal Code
3181
Country
Australia
Individual Site Status
Recruiting
Facility Name
Sheba Medical Center - PPDS
City
Ramat-Gan
ZIP/Postal Code
5262000
Country
Israel
Individual Site Status
Recruiting
Facility Name
The Catholic University of Korea - Seoul St. Mary's Hospital (Kangnam St. Mary's Hospital)
City
Seocho
ZIP/Postal Code
06591
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Samsung Medical Center - PPDS
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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).
Learn more about this trial
A Study Evaluating the Safety, Pharmacokinetics, and Activity of the Combination of Cevostamab and Elranatamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)
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