A Study to Evaluate the Safety, Pharmacokinetics, and Activity of XmAb24306 in Combination With Cevostamab in Participants With Relapsed/Refractory Multiple Myeloma

A Phase Ib, Open-label, Multicenter Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, and Activity of XmAb24306 in Combination With Cevostamab in Patients With Relapsed/Refractory Multiple Myeloma

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and activity of XmAb24306 in combination with cevostamab in participants with relapsed/refractory multiple myeloma (R/R MM) who have received a minimum of three prior treatments, including at least one immunomodulatory drug (IMiD), one proteasome inhibitor (PI), and one anti-CD38 monoclonal antibody.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Tocilizumab; Drug: Cevostamab; Drug: XmAb24306

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
• Denmark
  • Vejle, Denmark, 7100
    • Sygehus Lillebaelt - Vejle Sygehus
• Greece
  • Athens, Greece, 106 76
    • Evangelismos General Hospital of Athens
  • Athens, Greece, 115 28
    • University of Athens, Hematological Clinic,
• Israel
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center-Beilinson Campus
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center PPDS
• Norway
  • Oslo, Norway, N - 0424
    • Oslo University Hospital Rikshospitalet
• South Korea
  • Seoul, South Korea, 05505
    • Asan Medical Center - PPDS
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University
• Spain
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy of at least 12 weeks
• Participants must have received a minimum of 3 prior lines of therapy, including at least one PI, one IMiD, and an anti-CD38 monoclonal antibody.
• Documented evidence of progressive disease on or after the last prior therapy, or participants who were intolerant to the last prior therapy.
• Measurable disease, as defined by the protocol
• Participants agree to follow contraception or abstinence requirements as defined in the protocol

Exclusion Criteria:

• Any anti-cancer therapy within 3 weeks prior to initiation of study treatment with exception defined by the protocol
• Participants with autologous stem cell transplantation (SCT) within 100 days prior to first dose of study treatment
• Participants with prior allogeneic SCT or solid organ transplantation
• Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
• Active or history of autoimmune disease
• Participants with current or history of Central Nervous System (CNS) disease, or current CNS involvement by Multiple Myeloma (MM)
• Significant cardiovascular disease
• Participants with known clinically significant liver disease
• Symptomatic active pulmonary disease requiring supplemental oxygen
• Known active infection requiring intravenous anti-microbial therapy within 14 days prior to first study drug administration
• Any episode of active, symptomatic COVID-19 infection, or requiring treatment with IV antivirals for COVID-19 (not including COVID-19 primary prophylaxis) within 14 days, prior to first study treatment
• Other protocol defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Dose-Escalation and Expansion: XmAb24306+Cevostamab; Participants will receive escalating doses of XmAb24306 with a fixed dose regimen for cevostamab up to the maximum tolerated dose (MTD). After dose escalation has been completed, up to two expansion cohorts each investigating different XmAb24306 doses in combination with cevostamab may be enrolled.	Drug: Tocilizumab; Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.; Other Names: Actemra, RoActemra; Drug: Cevostamab; Cevostamab will be administered intravenously on a 28-day cycle, for up to one year of treatment depending on clinical response.; Other Names: RO7187797; Drug: XmAb24306; XmAb24306 will be administered intravenously on a 28-day cycle, for up to one year of treatment depending on clinical response.; Other Names: RO7310729
Experimental: Arm B: Single-Agent Cevostamab Expansion; Participants will receive cevostamab alone.	Drug: Tocilizumab; Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.; Other Names: Actemra, RoActemra; Drug: Cevostamab; Cevostamab will be administered intravenously on a 28-day cycle, for up to one year of treatment depending on clinical response.; Other Names: RO7187797

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage 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 Cytokine Release Syndrome (CRS), will be graded based on the American Society for Transplantation and Cellular Therapy (ASTCT) criteria.	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentration of XmAb24306		Up to approximately 3 years
Serum Concentration of Cevostamab		Up to approximately 3 years
Objective Response Rate (ORR)	ORR will be determined by the investigator according to International Myeloma Working Group (IMWG) criteria.	Up to approximately 3 years
Rate of Complete Response (CR)/ Stringent Complete Response (sCR)	Rate of CR/sCR will be determined by the investigator.	Up to approximately 3 years
Rate of Very Good Partial Response (VGPR)	Rate of VGPR will be determined by the investigator.	Up to approximately 3 years
Percentage of Participants With Anti-Drug Antibodies (ADA) to XmAb24306 and Cevostamab		Up to approximately 3 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2023
• Primary Completion (Estimated): November 18, 2026
• Study Completion (Estimated): November 18, 2026

Study Registration Dates

• First Submitted: December 2, 2022
• First Submitted That Met QC Criteria: December 2, 2022
• First Posted (Actual): December 12, 2022

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 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; tocilizumab
• Other Study ID Numbers: GO43980; 2022-001204-18 (EudraCT Number); 2023-505212-38-00 (Other Identifier: EU CT 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: No
• Studies a U.S. FDA-regulated device product: No