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)

Study Overview
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Brief Summary
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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 dose (RP2D) for the study treatment. The study consists of a safety lead-in stage, and an expansion stage.

Official Title
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An Open-Label, Multicenter, Phase Ib Trial Evaluating the Safety, Pharmacokinetics, and Activity of the Combination of Cevostamab and Elranatamab in Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Relapsed or Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: Cevostamab
* Drug: Elranatamab
* Drug: Tocilizumab


Participation Criteria
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Eligibility Criteria
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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

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: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Safety Lead-In Cohort<br>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. | Drug: Cevostamab<br>* Cevostamab solution for infusion will be administered as IV as specified in each treatment arm.<br>Drug: Elranatamab<br>* Elranatamab solution for injection will be administered SC as specified in each treatment arm.<br>Drug: Tocilizumab<br>* Tocilizumab will be used as rescue medication for participants who experience a cytokine release syndrome (CRS) event.<br>|
| Experimental: Dose Expansion Cohort<br>Participants will receive cevostamab, IV, in combination with elranatamab, 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. | Drug: Cevostamab<br>* Cevostamab solution for infusion will be administered as IV as specified in each treatment arm.<br>Drug: Elranatamab<br>* Elranatamab solution for injection will be administered SC as specified in each treatment arm.<br>Drug: Tocilizumab<br>* Tocilizumab will be used as rescue medication for participants who experience a cytokine release syndrome (CRS) event.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number 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 CRS will be graded based on the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading. Immune effector cell-associated neurotoxicity syndrome (ICANS) will be graded based on NCI CTCAE v5.0 and ASTCT Consensus Grading. | From signing of informed consent up to end of study (EOS) (approximately 36 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) as Determined by the Investigator per International Myeloma Working Group (IMWG) Criteria |  | Up to approximately 36 months | 
| Complete Response (CR)/ Stringent Complete Response (sCR) Rate as Determined by the Investigator per IMWG Criteria |  | Up to approximately 36 months | 
| Rate of Very Good Partial Response (VGPR) or Better, as Determined by the Investigator per IMWG Criteria |  | Up to approximately 36 months | 
| Progression-Free Survival as Determined by the Investigator per IMWG Criteria |  | Up to approximately 36 months | 
| Duration of Response (DOR) as Determined by the Investigator (for Participants who Achieve a Response of Partial Response (PR) or Better) |  | Up to approximately 36 months | 
| Time to First Response (for Participants who Achieve a Response of PR or Better) |  | Up to approximately 36 months | 
| Time to Best Response (for Participants who Achieve a Response of PR or Better) |  | Up to approximately 36 months | 
| Overall Survival (OS) |  | Up to approximately 36 months | 
| Serum Concentration of Cevostamab at Specified Timepoints |  | Up to approximately 36 months | 
| Serum Concentration of Elranatamab at Specified Timepoints |  | Up to approximately 36 months | 
| Number of Participants with Anti-Drug Antibody (ADA) Against Cevostamab |  | Up to approximately 36 months | 
| Number of Participants with ADA Against Elranatamab |  | Up to approximately 36 months |