Clinical trial NCT03340883: Safety and Tolerability of BION-1301 in Adults With Relapsed or Refractory Multiple Myeloma (MM)
Official title: A Phase 1/2, Dose Escalation, Safety and Tolerability Study of BION-1301 in Adults With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Chinook Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2017-11-14
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm study
Primary purpose: TREATMENT

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).

Eligibility criteria: Key Inclusion Criteria:

Individuals eligible to participate in this study must meet the following key criteria and additional criteria as specified in the protocol:

1. Male or female, aged ≥ 18 years
2. Confirmed diagnosis of MM per IMWG criteria
3. 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
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 1
6. Adequate organ and marrow function at Screening, as defined by the study protocol.

Key Exclusion Criteria:

1. Monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, Waldenstrom's macroglobulinemia, or IgM myeloma
2. Active plasma cell leukemia (˃ 2.0 × 109/L circulating plasma cells by standard differential)
3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
4. 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

Primary outcomes:
measure: Safety (Phase 1)
timeFrame: 28 days following first administration of BION-1301
measure: Recommended Phase 2 Dose (Phase 1)
timeFrame: Approximately 2 years
measure: Biomarkers (Phase 1 and 2)
timeFrame: Baseline and approximately 2 years
measure: Bioanalytical Measures (Phase 1 and Phase 2)
timeFrame: Baseline and approximately 2 years
measure: Safety Profile (Phase 2)
timeFrame: 28 days
measure: Response Rate (Phase 2)
timeFrame: Approximately 30 months
measure: Progression-Free Survival (Phase 2)
timeFrame: Approximately 30 months
measure: Overall Survival (Phase 2)
timeFrame: Approximately 30 months
Secondary outcomes:
Other outcomes:
Locations:
city: West Hollywood
country: United States
facility: James R. Berenson, MD, Inc
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute/Emory University
state: Georgia
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center James Cancer Hospital
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC (University of Pittsburgh Medical Center) Hillman Cancer Center
state: Pennsylvania
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital & The Medical College of Wisconsin
state: Wisconsin
Study officials:
References:
citation: Rajkumar SV, Harousseau JL, Durie B, Anderson KC, Dimopoulos M, Kyle R, Blade J, Richardson P, Orlowski R, Siegel D, Jagannath S, Facon T, Avet-Loiseau H, Lonial S, Palumbo A, Zonder J, Ludwig H, Vesole D, Sezer O, Munshi NC, San Miguel J; International Myeloma Workshop Consensus Panel 1. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011 May 5;117(18):4691-5. doi: 10.1182/blood-2010-10-299487. Epub 2011 Feb 3.