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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: XmAb24306
* Drug: Daratumumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation<br>Participants will receive escalating doses of XmAb24306 with daratumumab up to the maximum tolerated dose (MTD) | Drug: XmAb24306<br>* XmAb24306 will be given via intravenous (IV) infusion<br>* Other names: RO7310729;Drug: Daratumumab<br>* 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)<br>|
| Experimental: Dose expansion<br>Participants will receive XmAb24306 with daratumumab at the recommended phase 2 dose (RP2D) | Drug: XmAb24306<br>* XmAb24306 will be given via intravenous (IV) infusion<br>* Other names: RO7310729;Drug: Daratumumab<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |