A Safety Study of SEA-BCMA in Patients With Multiple Myeloma

Study Overview
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Brief Summary
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This trial will study SEA-BCMA to find out whether it is an effective treatment for multiple myeloma (MM) and what side effects (unwanted effects) may occur. The study will have several parts. In Parts A and B, participants get SEA-BCMA by itself. This part of the study will find out how much SEA-BCMA should be given for treatment and how often. It will also find out how safe the treatment is and how well it works. In Part C of the study, participants will get SEA-BCMA and dexamethasone. In Part D, participants will get SEA-BCMA, dexamethasone, and pomalidomide. Dexamethasone and pomalidomide are both drugs that can be used to treat multiple myeloma. These parts of the study will find out whether these drugs are safe when used together.

Official Title
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A Phase 1 Study of SEA-BCMA in Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: SEA-BCMA
* Drug: dexamethasone
* Drug: pomalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of MM Must have MM that is relapsed or refractory Has received a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody Measurable disease, as defined by at least one of the following: (1) serum M protein 0.5 g/dL or higher, (2) urine M protein 200 mg/24 hour or higher, and (3) serum immunoglobulin free light chain (FLC) 10 mg/dL or higher and abnormal serum immunoglobulin kappa lambda FLC ratio. Eastern Cooperative Oncology Group (ECOG) status score of 0 or 1 Life expectancy of greater than 3 months in the opinion of the investigator Adequate hematologic, renal, and hepatic function Exclusion Criteria: Parts A and D: Prior treatment with a BCMA-directed therapy History of another malignancy within 3 years Active cerebral or meningeal disease related to the underlying malignancy Uncontrolled Grade 3 or higher infection Prior antitumor therapy that is not completed at least 4 weeks prior to first dose of study drug, or at least 2 weeks if progressing. Prior CAR-T-cell therapy must be completed 8 weeks before first dose of study drug. Combination therapy only: Known intolerance to corticosteroids Uncontrolled psychoses

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Parts A and B: SEA-BCMA Monotherapy<br>SEA-BCMA | Drug: SEA-BCMA<br>* Given into the vein (IV; intravenously)<br>|
| Experimental: Part C: SEA-BCMA + Dexamethasone Combination Therapy<br>SEA-BCMA + dexamethasone | Drug: SEA-BCMA<br>* Given into the vein (IV; intravenously)<br>Drug: dexamethasone<br>* Given by mouth (orally) or by IV<br>|
| Experimental: Part D: SEA-BCMA + Pomalidomide + Dexamethasone Combination Therapy<br>SEA-BCMA + dexamethasone + pomalidomide | Drug: SEA-BCMA<br>* Given into the vein (IV; intravenously)<br>Drug: dexamethasone<br>* Given by mouth (orally) or by IV<br>Drug: pomalidomide<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) | Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. | Through 30-37 days following last dose, up to approximately 3 years | 
| Number of participants with laboratory abnormalities by grade | Grades for laboratory abnormalities will be evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), version 4.03 | Through 30-37 days following last dose, up to approximately 3 years | 
| Incidence of dose-limiting toxicities (DLTs) | To be summarized using descriptive statistics. | Through up to 28 days following first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) outcome: Cmax (maximum serum concentration) | To be summarized using descriptive statistics. | Through 30-37 days following last dose, up to approximately 3 years | 
| PK outcome: AUC (area under the serum concentration-time curve) | To be summarized using descriptive statistics. | Through 84 days following first dose | 
| Incidence of SEA-BCMA antitherapeutic antibodies (ATA) |  | Through 30-37 days following last dose, up to approximately 4 years | 
| Best response per the IMWG uniform response criteria | International Myeloma Working Group (IMWG) | Up to approximately 5 years | 
| Objective response rate (ORR) | The proportion of patients with stringent complete response, complete response, very good partial response, or partial response per investigator | Up to approximately 4 years | 
| Duration of objective response (OR) | The time from first documentation of OR to the first documentation of disease progression or death due to any cause | Up to approximately 4 years | 
| Duration of complete response (CR) | The time from first documentation of CR to the first documentation of disease progression or death due to any cause | Up to approximately 4 years | 
| Progression-free survival (PFS) | The time from the start of study treatment to the first documentation of disease progression or death due to any cause | Up to approximately 4 years | 
| Overall survival (OS) | The time from the start of study treatment to the date of death due to any cause | Up to approximately 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RRMM, Antibodies, monoclonal, Antigens, BCMA, Immunotherapy, Hematologic diseases, Myeloma, Seattle Genetics