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

Study Overview
=================
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.

Official Title
-----------------
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

Conditions
-----------------
Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: Cevostamab
* Drug: XmAb24306
* Drug: Tocilizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: Arm A: Dose-Escalation and Expansion: XmAb24306+Cevostamab<br>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<br>* Cevostamab will be administered intravenously on a 28-day cycle, for up to one year of treatment depending on clinical response.<br>* Other names: RO7187797;Drug: XmAb24306<br>* XmAb24306 will be administered intravenously on a 28-day cycle, for up to one year of treatment depending on clinical response.<br>* Other names: RO7310729;Drug: Tocilizumab<br>* Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.<br>* Other names: Actemra, RoActemra;|
| Experimental: Arm B: Single-Agent Cevostamab Expansion<br>Participants will receive cevostamab alone. | Drug: Cevostamab<br>* Cevostamab will be administered intravenously on a 28-day cycle, for up to one year of treatment depending on clinical response.<br>* Other names: RO7187797;Drug: Tocilizumab<br>* Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.<br>* Other names: Actemra, RoActemra;|

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 |