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

Phase 1
Active, not recruiting
Conditions
Multiple Myeloma
Interventions
Registration Number
NCT05646836
Lead Sponsor
Genentech, Inc.
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
90
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 & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Arm A: Dose-Escalation and Expansion: XmAb24306+CevostamabXmAb24306Participants 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.
Arm A: Dose-Escalation and Expansion: XmAb24306+CevostamabTocilizumabParticipants 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.
Arm A: Dose-Escalation and Expansion: XmAb24306+CevostamabCevostamabParticipants 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.
Arm B: Single-Agent Cevostamab ExpansionTocilizumabParticipants will receive cevostamab alone.
Arm B: Single-Agent Cevostamab ExpansionCevostamabParticipants will receive cevostamab alone.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants with Adverse Events (AEs)Up to approximately 3 years

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.

Secondary Outcome Measures
NameTimeMethod
Rate of Complete Response (CR)/ Stringent Complete Response (sCR)Up to approximately 3 years

Rate of CR/sCR will be determined by the investigator.

Serum Concentration of XmAb24306Up to approximately 3 years
Serum Concentration of CevostamabUp to approximately 3 years
Objective Response Rate (ORR)Up to approximately 3 years

ORR will be determined by the investigator according to International Myeloma Working Group (IMWG) criteria.

Percentage of Participants With Anti-Drug Antibodies (ADA) to XmAb24306 and CevostamabUp to approximately 3 years
Rate of Very Good Partial Response (VGPR)Up to approximately 3 years

Rate of VGPR will be determined by the investigator.

Trial Locations

Locations (13)

Peter Maccallum Cancer Centre

🇦🇺

Melbourne, Victoria, Australia

Alfred Hospital

🇦🇺

Melbourne, Victoria, Australia

Sygehus Lillebaelt - Vejle Sygehus

🇩🇰

Vejle, Denmark

Evangelismos General Hospital of Athens

🇬🇷

Athens, Greece

University of Athens, Hematological Clinic,

🇬🇷

Athens, Greece

Rabin Medical Center-Beilinson Campus

🇮🇱

Petach Tikva, Israel

Tel Aviv Sourasky Medical Center PPDS

🇮🇱

Tel Aviv-Yafo, Israel

Clinica Universidad de Navarra

🇪🇸

Pamplona, Navarra, Spain

Hospital Universitari i Politecnic La Fe de Valencia

🇪🇸

Valencia, Spain

Oslo University Hospital Rikshospitalet

🇳🇴

Oslo, Norway

Royal Adelaide Hospital

🇦🇺

Adelaide, South Australia, Australia

Severance Hospital, Yonsei University

🇰🇷

Seoul, Korea, Republic of

Asan Medical Center - PPDS

🇰🇷

Seoul, Korea, Republic of

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