Cevostamab in Combination With Pomalidomide and Dexamethasone Versus Standard of Care in Participants With Previously Treated Multiple Myeloma (CEVOLUTION)

A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Cevostamab in Combination With Pomalidomide and Dexamethasone Versus Standard of Care in Patients With Multiple Myeloma Who Have Received One to Three Prior Lines of Therapy

The purpose of this study is to assess the efficacy and safety of cevostamab in combination with pomalidomide and dexamethasone (CevosPd) versus standard of care (SOC) in participants with multiple myeloma (MM) who have received one to three prior lines of therapy and have been exposed to an anti-CD38 monoclonal antibody (mAb) and lenalidomide.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Cevostamab; Drug: Pomalidomide; Drug: Dexamethasone; Drug: Daratumumab; Drug: Elotuzumab; Drug: Carfilzomib

• Study Type: Interventional
• Enrollment (Estimated): 380
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: CO46096 https://forpatients.roche.com/; Phone Number: 888-662-6728; Email: global-roche-genentech-trials@gene.com

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • Recruiting
    • Auxilio Mutuo Cancer Center
• United States
  • California
    • Duarte, California, United States, 91010-3012
      • Recruiting
      • City of Hope National Medical Center
    • Irvine, California, United States, 92618
      • Recruiting
      • City of Hope - Lennar Foundation Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Recruiting
      • Winship Cancer Institute of Emory University

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 at screening and immediately prior to start of administration of study treatment.
• Individuals with ECOG Performance Status of 2 solely due to local symptoms of myeloma (e.g., pain) are eligible
• MM diagnosis according to the International Myeloma Working Group (IMWG) diagnostic criteria
• Received one to three lines of prior therapy that included at least two consecutive cycles of either of the following: A regimen containing an anti-CD38 therapy, a regimen containing lenalidomide
• Participants must have measurable disease during screening

Exclusion Criteria:

• Known history of amyloidosis (e.g., positive Congo Red stain or equivalent in tissue biopsy or documented within serum amyloid P component scan)
• Plasma cell leukemia or circulating plasma cell count exceeding 500 cells/liter (L) or 5% of the peripheral blood white cells
• GI disease that might significantly alter absorption of oral drugs
• Participants must not have any ongoing CNS disease or non-secretory myeloma

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cevostamab + Pomalidomide + Dexamethasone; Cevostamab will be administered intravenously on a 21-day cycle in cycle 1 and on a 28-day cycle from cycle 2 onwards. Pomalidomide will be administered orally (PO) on a 28-day cycle from cycle 2 onwards. Dexamethasone will be administered as a premedication prior to cevostamab.	Drug: Cevostamab; Participants will receive cevostamab IV as per the schedule given in the protocol.; Drug: Pomalidomide; Participants will receive pomalidomide tablet orally PO as per the schedule given in the protocol.; Drug: Dexamethasone; Participants will receive dexamethasone tablet orally PO or IV as per the schedule given in the protocol.
Active Comparator: Standard of Care (SOC); Participants will receive investigator's choice of one SOC regimen.	Drug: Pomalidomide; Participants will receive pomalidomide tablet orally PO as per the schedule given in the protocol.; Drug: Dexamethasone; Participants will receive dexamethasone tablet orally PO or IV as per the schedule given in the protocol.; Drug: Daratumumab; Participants will receive daratumumab SC as per the schedule given in the protocol.; Drug: Elotuzumab; Participants will receive elotuzumab IV as per the schedule given in the protocol.; Drug: Carfilzomib; Participants will receive carfilzomib IV as per the schedule given in the protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Minimal Residual Disease (MRD)-Negative Complete Response (CR) Rate	Up to 1 year after the last participant is randomized
Progression-Free Survival (PFS)	Up to 5 years after the last participant is randomized

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)		Up to 5 years after the last participant is randomized
Very Good Partial Response (VGPR) or Better Rate		Up to 5 years after the last participant is randomized
Overall Survival (OS)		Up to 5 years after the last participant is randomized
Time to Confirmed Deterioration in the Disease Symptoms Scale as Assessed by the European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ)-Multiple Myeloma Module 20 (MY20)	Primary domains: fatigue, pain, physical functioning, cognitive functioning and global health status.	Up to 5 years after the last participant is randomized
Overall Response Rate (ORR)		Up to 5 years after the last participant is randomized
Complete Response (CR) Rate		Up to 5 years after the last participant is randomized
Time to Response (TTR)		Up to 5 years after the last participant is randomized
Time to Best Response (TTBR)		Up to 5 years after the last participant is randomized
Duration of Response (DOR)		Up to 5 years after the last participant is randomized
Progression-Free Survival 2 (PFS2)		Up to 5 years after the last participant is randomized
Overall MRD-Negative Complete Response Rate		Up to 5 years after the last participant is randomized
Overall MRD-Negative Rate		Up to 5 years after the last participant is randomized
Sustained MRD-Negative CR Rate		At 6, 12, and 24 months
Percentage of Participants With Adverse Events (AEs)		Up to 5 years after the last participant is randomized
Tolerability as Assessed by the Incidence of Dose Interruptions, Dose Reductions, Dose Intensity, and Treatment Discontinuation		Up to 5 years after the last participant is randomized
Number of Participants With Presence, Frequency of Occurrence, Severity, and/or Degree of Interference With Daily Function of Shortness of Breath, Cough, Heart Palpitations, Rash, Dizziness, and Nausea Assessed NCI PRO-CTCAE		Up to 5 years after the last participant is randomized
Change From Baseline in Shortness of Breath, Cough, Heart Palpitations, Rash, Dizziness, and Nausea Assessed by the National Cancer Institute Patient Reported Outcomes Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE)		Baseline and up to 5 years after the last participant is randomized
Change From Cycle 1 Day 8 in Treatment-Related Side Effect Bother as Assessed by the Functional Assessment of Cancer Therapy-General, General Population 5 (FACTG GP5)		At Day 8 of Cycle 1, up to 5 years after the last participant is randomized. Cycle 1 is 21 days.
Change From Baseline in the Disease Symptom Scale of the EORTC QLQ-MY20		Baseline and Up to 5 years after the last participant is randomized
Change from Baseline in the Global Health Status/Quality of Life (GHS/QoL) of the EORTC QLQ-Core 30 (C30)		Baseline and Up to 5 years after the last participant is randomized
Time to Confirmed Deterioration in GHS/QoL as Assessed by the EORTC QLQ-C30		Up to 5 years after the last participant is randomized
Change From Baseline in Fatigue as Assessed by the EORTC QLQ-C30		Baseline and up to 5 years after the last participant is randomized
Time to Confirmed Deterioration in Fatigue as Assessed by the EORTC QLQ-C30		Up to 5 years after the last participant is randomized
Percentage of Participants Experiencing Clinically Meaningful Improvement in Disease Symptoms as Assessed by the EORTC QLQ-MY20		Up to 5 years after the last participant is randomized
Percentage of Participants Experiencing Clinically Meaningful Improvement in GHS/QoL as Assessed by the EORTC QLQ-C30		Up to 5 years after the last participant is randomized
Percentage of Participants Experiencing Clinically Meaningful Improvement in Fatigue as Assessed by the EORTC QLQ-C30		Up to 5 years after the last participant is randomized
Percentage of Participants with Anti-Drug Antibodies (ADAs) to Cevostamab at Baseline and with ADAs to Cevostamab During the Study		Baseline and up to 5 years after the last participant is randomized

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): January 31, 2033

Study Registration Dates

• First Submitted: April 22, 2026
• First Submitted That Met QC Criteria: April 22, 2026
• First Posted (Actual): April 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Dexamethasone; carfilzomib; pomalidomide; elotuzumab; daratumumab
• Other Study ID Numbers: CO46096; 2025-524028-23-00 (Ctis)

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