A Study to Evaluate the Safety, Pharmacokinetics, and Activity of XmAb24306 in Combination With Cevostamab in Participants With Relapsed/Refractory Multiple Myeloma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| 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: Cevostamab
Cevostamab will be administered intravenously on a 28-day cycle, for up to one year of treatment depending on clinical response.
Other Names:
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:
Drug: Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
Other Names:
|
| Experimental: Arm B: Single-Agent Cevostamab Expansion Participants will receive cevostamab alone. |
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:
Drug: Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- Serum Concentration of XmAb24306 [Up to approximately 3 years]
- Serum Concentration of Cevostamab [Up 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.
- Rate of Complete Response (CR)/ Stringent Complete Response (sCR) [Up to approximately 3 years]
Rate of CR/sCR will be determined by the investigator.
- Rate of Very Good Partial Response (VGPR) [Up to approximately 3 years]
Rate of VGPR will be determined by the investigator.
- Percentage of Participants With Anti-Drug Antibodies (ADA) to XmAb24306 and Cevostamab [Up to approximately 3 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
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Life expectancy of at least 12 weeks
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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.
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Documented evidence of progressive disease on or after the last prior therapy, or participants who were intolerant to the last prior therapy.
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Measurable disease, as defined by the protocol
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Participants agree to follow contraception or abstinence requirements as defined in the protocol
Exclusion Criteria:
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Any anti-cancer therapy within 3 weeks prior to initiation of study treatment with exception defined by the protocol
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Participants with autologous stem cell transplantation (SCT) within 100 days prior to first dose of study treatment
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Participants with prior allogeneic SCT or solid organ transplantation
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Active or history of autoimmune disease
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Participants with current or history of Central Nervous System (CNS) disease, or current CNS involvement by Multiple Myeloma (MM)
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Significant cardiovascular disease
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Participants with known clinically significant liver disease
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Symptomatic active pulmonary disease requiring supplemental oxygen
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Known active infection requiring intravenous anti-microbial therapy within 14 days prior to first study drug administration
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Other protocol defined inclusion/exclusion criteria may apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Evangelismos General Hospital of Athens | Athens | Greece | 106 76 | |
| 2 | University of Athens Medical School - Regional General Hospital Alexandra | Athens | Greece | 115 28 |
Sponsors and Collaborators
- Genentech, Inc.
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GO43980
- 2022-001204-18