A Study Evaluating the Safety, Pharmacokinetics, and Activity of the Combination of Cevostamab and Elranatamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)

Genentech

Status and phase: Enrolling; Phase 1

Conditions: Relapsed or Refractory Multiple Myeloma

Treatments: Drug: Elranatamab; Drug: Cevostamab; Drug: Tocilizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05927571

GO43979

2023-504657-13-00 (Other Identifier)

Details and patient eligibility

About

The purpose of the study is to evaluate safety and tolerability of the combination of cevostamab plus elranatamab and also determine the recommended Phase II regimen (RP2R) for the study treatment. The study consists of a safety lead-in stage, and an expansion stage.

Enrollment: 120 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
• Diagnosis of R/R MM per IMWG criteria
• For female participants of childbearing potential: agreement to remain abstinent or use contraception
• For male participants: agreement to remain abstinent or use a condom

Exclusion criteria

• Prior treatment with cevostamab or another agent targeting fragment crystallizable receptor-like 5 (FcRH5)
• Prior treatment with elranatamab
• Prior allogeneic stem cell transplantation (SCT)
• Absolute plasma cell count exceeding 500 per milliliter (mL) or 5% of the peripheral blood white cells
• Diagnosis of Waldenström macroglobulinemia or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome
• Participants with known history of amyloidosis
• History of autoimmune disease
• History of confirmed progressive multifocal leukoencephalopathy
• Peripheral motor polyneuropathy of prespecified grade
• Known or suspected chronic cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) infection
• Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
• Acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• Human immunodeficiency virus (HIV) seropositivity
• History of central nervous system (CNS) myeloma disease
• Significant cardiovascular disease

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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120 participants in 3 patient groups

Safety Lead-In Cohort

Experimental group

Description:

Participants will receive cevostamab, intravenously (IV), in combination with elranatamab, subcutaneously (SC), with step-up dosing of each drug in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first.

Treatment:

Drug: Tocilizumab

Drug: Elranatamab

Drug: Cevostamab

Dose Expansion Cohort (Combined Therapy)

Experimental group

Description:

Participants will receive cevostamab, IV, in combination with elranatamab, SC, with step-up dosing in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first.

Treatment:

Drug: Tocilizumab

Drug: Elranatamab

Drug: Cevostamab

Dose Expansion Cohort (Monotherapy)

Experimental group

Description:

Participants will receive elranatamab SC, with step-up dosing in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity.

Treatment:

Drug: Elranatamab