Safety and Tolerability of BION-1301 in Adults With Relapsed or Refractory Multiple Myeloma (MM)
- Conditions
- Multiple Myeloma
- Interventions
- Biological: BION-1301
- Registration Number
- NCT03340883
- Lead Sponsor
- Chinook Therapeutics, Inc.
- Brief Summary
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
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).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 21
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BION-1301 BION-1301 BION-1301 will be administered once every 2 weeks as an intravenous (IV) infusion.
- Primary Outcome Measures
Name Time Method Recommended Phase 2 Dose (Phase 1) Approximately 2 years Recommended Phase 2 Dose RP2D of BION-1301 when administered as a single-agent
Biomarkers (Phase 1 and 2) Baseline and approximately 2 years Biomarkers such as soluble a proliferation inducing ligand (APRIL; TNFSF13); soluble B cell maturation antigen (BCMA; TNFRSF17)
Safety Profile (Phase 2) 28 days BION-1301 safety profile based on incidence of TEAEs (treatment emergent adverse events), changes in safety parameters, and unacceptable toxicities
Progression-Free Survival (Phase 2) Approximately 30 months 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
Safety (Phase 1) 28 days following first administration of BION-1301 Number of patients reporting treatment-related adverse events that qualify as dose-limiting toxicities (DLTs) of BION-1301 as a single agent
Bioanalytical Measures (Phase 1 and Phase 2) Baseline and approximately 2 years Relative change in serum and urine M-protein levels defined as the maximum reduction from baseline
Response Rate (Phase 2) Approximately 30 months 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)
Overall Survival (Phase 2) Approximately 30 months Overall survival (OS) defined as the time from first dose of study drug to date of death due to any cause
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (7)
James R. Berenson, MD, Inc
🇺🇸West Hollywood, California, United States
Winship Cancer Institute/Emory University
🇺🇸Atlanta, Georgia, United States
Ohio State University Wexner Medical Center James Cancer Hospital
🇺🇸Columbus, Ohio, United States
UPMC (University of Pittsburgh Medical Center) Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
Froedtert Hospital & The Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States