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)

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

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 regimen (RP2R) for the study treatment. The study consists of a safety lead-in stage, and an expansion stage.

Study Overview

• Status: Recruiting
• Conditions: Relapsed or Refractory Multiple Myeloma
• Intervention / Treatment: Drug: Cevostamab; Drug: Elranatamab; Drug: Tocilizumab

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: GO43979 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com
• Study Contact Backup: Name: Fastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Royal Prince Alfred Hospital
    • Waratah, New South Wales, Australia, 2298
      • Recruiting
      • Calvary Mater Newcastle
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital;Haematology Clinical Trials Unit
  • Victoria
    • Melbourne, Victoria, Australia, 3065
      • Recruiting
      • St. Vincent's Hospital Melbourne
    • Prahan, Victoria, Australia, 3181
      • Recruiting
      • The Alfred Hospital
• Israel
  • Haifa, Israel, 3109600
    • Recruiting
    • Rambam Health Care Campus
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah University Hospital - Ein Kerem
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Tel Aviv Sourasky Medical Center PPDS
  • Central District
    • Ramat Gan, Central District, Israel, 5262100
      • Recruiting
      • The Chaim Sheba Medical Center - PPDS
• South Korea
  • Seocho, South Korea, 06591
    • Recruiting
    • The Catholic University of Korea - Seoul St. Mary's Hospital (Kangnam St. Mary's Hospital)
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 03722
    • Recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center - PPDS
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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
• Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Lead-In Cohort; 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.	Drug: Cevostamab; Cevostamab solution for infusion will be administered as IV as specified in each treatment arm.; Drug: Elranatamab; Elranatamab solution for injection will be administered SC as specified in each treatment arm.; Drug: Tocilizumab; Tocilizumab will be used as rescue medication for participants who experience a cytokine release syndrome (CRS) event.
Experimental: Dose Expansion Cohort (Combined Therapy); Participants will receive cevostamab, IV, in combination with elranatamab, SC, with step-up dosing 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.	Drug: Cevostamab; Cevostamab solution for infusion will be administered as IV as specified in each treatment arm.; Drug: Elranatamab; Elranatamab solution for injection will be administered SC as specified in each treatment arm.; Drug: Tocilizumab; Tocilizumab will be used as rescue medication for participants who experience a cytokine release syndrome (CRS) event.
Experimental: Dose Expansion Cohort (Monotherapy); Participants will receive elranatamab SC, with step-up dosing in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity.	Drug: Elranatamab; Elranatamab solution for injection will be administered SC as specified in each treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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). The severity of CRS, immune effector cell-associated neurotoxicity syndrome (ICANS) and hemophagocytic lymphohistiocytosis (HLH) will be graded based on the American Society for Transplantation and Cellular Therapy (ASTCT) Grading Scales.	From signing of informed consent up to end of study (EOS) (approximately 36 months)
Recommended Phase II Regimen (RP2R)		Up to approximately 36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR) as Determined by the Investigator per International Myeloma Working Group (IMWG) Criteria	Up to approximately 36 months
Complete Response (CR)/ Stringent Complete Response (sCR) Rate as Determined by the Investigator per IMWG Criteria	Up to approximately 36 months
Rate of Very Good Partial Response (VGPR) or Better, as Determined by the Investigator per IMWG Criteria	Up to approximately 36 months
Progression-Free Survival as Determined by the Investigator per IMWG Criteria	Up to approximately 36 months
Duration of Response (DOR) as Determined by the Investigator (for Participants who Achieve a Response of Partial Response (PR) or Better)	Up to approximately 36 months
Time to First Response (for Participants who Achieve a Response of PR or Better)	Up to approximately 36 months
Time to Best Response (for Participants who Achieve a Response of PR or Better)	Up to approximately 36 months
Overall Survival (OS)	Up to approximately 36 months
Serum Concentration of Cevostamab at Specified Timepoints	Up to approximately 36 months
Serum Concentration of Elranatamab at Specified Timepoints	Up to approximately 36 months
Number of Participants with Anti-Drug Antibody (ADA) Against Cevostamab	Up to approximately 36 months
Number of Participants with ADA Against Elranatamab	Up to approximately 36 months

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

Helpful Links

• Please use this form to submit your questions for a faster response: https://www.gene.com/contact-us/submit-medical-inquiry. Do not include or attach any medical records when emailing or completing the form. A nurse will respond within 24 business hours.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2023
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: June 22, 2023
• First Submitted That Met QC Criteria: June 22, 2023
• First Posted (Actual): July 3, 2023

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Multiple Myeloma; tocilizumab
• Other Study ID Numbers: GO43979; 2023-504657-13-00 (Ctis: EU Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• 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