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

Genentech

Status and phase: Active, not recruiting; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: XmAb24306; Drug: Cevostamab; Drug: Tocilizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05646836

2022-001204-18 (EudraCT Number)

GO43980

2023-505212-38-00 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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90 participants in 2 patient groups

Arm A: Dose-Escalation and Expansion: XmAb24306+Cevostamab

Experimental group

Description:

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.

Treatment:

Drug: Tocilizumab

Drug: XmAb24306

Drug: Cevostamab

Arm B: Single-Agent Cevostamab Expansion

Experimental group

Description:

Participants will receive cevostamab alone.

Treatment:

Drug: Tocilizumab

Drug: Cevostamab