Safety and Tolerability of BION-1301 in Adults With Relapsed or Refractory Multiple Myeloma (MM)

Study Overview
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Brief Summary
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This is a Phase 1/2 study designed to evaluate the safety and tolerability of BION-1301 in adults with relapsed or refractory multiple myeloma whose disease has progressed after 3 or more prior systemic therapies.

Detailed Description
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An open-label, multi-center, dose-selection Phase 1/2 study (also referred to as ADU-CL-16) evaluating BION-1301, a humanized monoclonal antibody directed against APRIL for the treatment of relapsed or refractory MM. This first-in-human study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and initial clinical activity of BION-1301 administered as a single agent. The study will be conducted in 2 parts. Phase 1 is dose escalation and seeks to determine the recommended phase 2 dose (RP2D). Once an RP2D is identified, Phase 2 of the study will open and continue to evaluate the safety and preliminary efficacy of BION-1301 administered at selected dose level(s). The population for this study will consist of adults with relapsed or refractory MM whose disease has progressed after at least 3 prior systemic therapies. BION-1301 will be administered in 28-day cycles; the dosing interval will be once every two weeks (Q2W).

Official Title
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A Phase 1/2, Dose Escalation, Safety and Tolerability Study of BION-1301 in Adults With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: BION-1301


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Individuals eligible to participate in this study must meet the following key criteria and additional criteria as specified in the protocol: Male or female, aged ≥ 18 years Confirmed diagnosis of MM per IMWG criteria Measurable disease as defined by one or more of the following: Serum M-protein ≥ 0.5 g/dL Urine M-protein ≥ 200 mg/24 hours Serum Free Light Chain (FLC) assay: involved FLC level ≥ 10 mg/dL provided serum FLC ratio is abnormal In cases where SPEP is unreliable, serum quantitative immunoglobulin (qIgA) ≥ 750 mg/dL (0.75 g/dL) is acceptable Relapsed or refractory (Rajkumar, 2011) to 3 or more different prior lines of therapy for MM, including immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), chemotherapies, or monoclonal antibodies, and not a candidate for, or intolerant to established therapy known to provide clinical benefit. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 1 Adequate organ and marrow function at Screening, as defined by the study protocol. Key Exclusion Criteria: Monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, Waldenstrom's macroglobulinemia, or IgM myeloma Active plasma cell leukemia (˃ 2.0 × 109/L circulating plasma cells by standard differential) POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) Prior treatment directed to B-cell Activating Factor (BAFF; BLyS), B-cell Maturation Antigen (BCMA;TNFSF17) or Transmembrane Activator and CAML interactor (TACI; TNFSF13B), including antibodies or BCMA- or TACI-directed Chimeric Antigen Receptor (CAR)-T cell therapy

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
Intervention Model: Single Group Assignment
Interventional Model Description: Single arm study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BION-1301<br>BION-1301 will be administered once every 2 weeks as an intravenous (IV) infusion. | Biological: BION-1301<br>* a solution for intravenous (IV) administration, diluted and administered Q2W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (Phase 1) | Number of patients reporting treatment-related adverse events that qualify as dose-limiting toxicities (DLTs) of BION-1301 as a single agent | 28 days following first administration of BION-1301 | 
| Recommended Phase 2 Dose (Phase 1) | Recommended Phase 2 Dose RP2D of BION-1301 when administered as a single-agent | Approximately 2 years | 
| Biomarkers (Phase 1 and 2) | Biomarkers such as soluble a proliferation inducing ligand (APRIL; TNFSF13); soluble B cell maturation antigen (BCMA; TNFRSF17) | Baseline and approximately 2 years | 
| Bioanalytical Measures (Phase 1 and Phase 2) | Relative change in serum and urine M-protein levels defined as the maximum reduction from baseline | Baseline and approximately 2 years | 
| Safety Profile (Phase 2) | BION-1301 safety profile based on incidence of TEAEs (treatment emergent adverse events), changes in safety parameters, and unacceptable toxicities | 28 days | 
| Response Rate (Phase 2) | Objective response rate (ORR) based on International Myeloma Working Group (IMWG) uniform response criteria of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) | Approximately 30 months | 
| Progression-Free Survival (Phase 2) | Progression-free survival (PFS) defined as time from first dose of study drug to date of first tumor progression or death due to any cause | Approximately 30 months | 
| Overall Survival (Phase 2) | Overall survival (OS) defined as the time from first dose of study drug to date of death due to any cause | Approximately 30 months |