A Study to Evaluate the Safety and Pharmacokinetics of XMAB24306 in Combination With Daratumumab in Participants With Relapsed/Refractory Multiple Myeloma

A Phase Ib, Open-Label, Multicenter, Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of XMAB24306 in Combination With Daratumumab in Patients With Relapsed/Refractory Multiple Myeloma

This study will evaluate the safety, tolerability, pharmacokinetics, and activity of XmAb24306 in combination with a multiple myeloma (MM)-targeting monoclonal antibody capable of inducing antibody-dependent cellular toxicity (ADCC) in participants with relapsed or refractory (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: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: XmAb24306; Drug: Daratumumab

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
• Denmark
  • South Denmark
    • Odense C, South Denmark, Denmark, 5000
      • Odense Universitetshospital
    • Vejle, South Denmark, Denmark, 7100
      • Sygehus Lillebælt, Vejle
• Norway
  • Oslo, Norway, 0450
    • Oslo Universitetssykehus HF
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitario Germans Trias i Pujol

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Life expectancy of at least 12 weeks
• Measurable disease, as defined by the protocol
• 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
• Best response of stable disease or better with at least one prior anti-CD38 monoclonal antibody containing line of treatment

Exclusion Criteria:

• Any anti-cancer therapy within 3 weeks prior to initiation of study treatment, with exceptions defined by the protocol
• Prior allogeneic stem cell or solid organ transplantation
• Autologous stem cell transplantation within 100 days prior to initiation of study treatment
• Significant cardiovascular disease
• Known clinically significant liver disease
• Active or history of autoimmune disease or immune deficiency
• Known active infection requiring IV anti-microbial therapy within 14 days prior to first study drug administration
• Primary or secondary plasma cell leukemia
• Current CNS involvement by MM
• 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: Dose escalation; Participants will receive escalating doses of XmAb24306 with daratumumab up to the maximum tolerated dose (MTD)	Drug: XmAb24306; XmAb24306 will be given via intravenous (IV) infusion; Other Names: RO7310729; Drug: Daratumumab; Participants will receive daratumumab via subcutaneous (SC) injection every week for Cycles 1-4, every 2 weeks for Cycles 5-12, and every 4 weeks thereafter (cycle length = 2 weeks for Cycles 1-12 and 4 weeks thereafter)
Experimental: Dose expansion; Participants will receive XmAb24306 with daratumumab at the recommended phase 2 dose (RP2D)	Drug: XmAb24306; XmAb24306 will be given via intravenous (IV) infusion; Other Names: RO7310729; Drug: Daratumumab; Participants will receive daratumumab via subcutaneous (SC) injection every week for Cycles 1-4, every 2 weeks for Cycles 5-12, and every 4 weeks thereafter (cycle length = 2 weeks for Cycles 1-12 and 4 weeks thereafter)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants with adverse events (AEs)	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum concentration of XmAb24306	Baseline to approximately 3 years
Objective response rate (ORR)	Baseline to approximately 3 years
Prevalence of XmAb24306 anti-drug antibodies (ADAs)	Baseline to approximately 3 years
Incidence of XmAb24306 ADAs	Baseline 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): April 28, 2022
• Primary Completion (Actual): July 10, 2024
• Study Completion (Actual): July 10, 2024

Study Registration Dates

• First Submitted: February 1, 2022
• First Submitted That Met QC Criteria: February 14, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 13, 2025
• Last Verified: February 1, 2025

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; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Daratumumab
• Other Study ID Numbers: GO43073

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No