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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03340883
• Other study ID #: ADU-CL-16
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 15, 2017
• Est. completion date: July 9, 2019

Study information

• Verified date: March 2021
• Source: Chinook Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: July 9, 2019
• Est. primary completion date: June 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Biological:
• BION-1301
a solution for intravenous (IV) administration, diluted and administered Q2W

Locations

Country	Name	City	State
United States	Winship Cancer Institute/Emory University	Atlanta	Georgia
United States	Ohio State University Wexner Medical Center James Cancer Hospital	Columbus	Ohio
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Froedtert Hospital & The Medical College of Wisconsin	Milwaukee	Wisconsin
United States	UPMC (University of Pittsburgh Medical Center) Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Swedish Medical Center	Seattle	Washington
United States	James R. Berenson, MD, Inc	West Hollywood	California

Sponsors (1)

Lead Sponsor	Collaborator
Chinook Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Recommended Phase 2 Dose (Phase 1)	Recommended Phase 2 Dose RP2D of BION-1301 when administered as a single-agent	Approximately 2 years
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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