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

• Sponsor: Chinook Therapeutics, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03340883
• Collaborator: (none)
• Enrollment: 21
• Locations: 7
• Arm: 1
• Actual Duration (Months): 19.7
• Patients Per Site: 3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Biological: BION-1301	Phase 1/Phase 2

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single arm studySingle arm study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2, Dose Escalation, Safety and Tolerability Study of BION-1301 in Adults With Relapsed or Refractory Multiple Myeloma
• Actual Study Start Date: Nov 15, 2017
• Actual Primary Completion Date: Jun 13, 2019
• Actual Study Completion Date: Jul 9, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

2. Recommended Phase 2 Dose (Phase 1) [Approximately 2 years]

   Recommended Phase 2 Dose RP2D of BION-1301 when administered as a single-agent

3. 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)

4. 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

5. 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

6. 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)

7. 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

8. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. 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.

2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 1

3. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	James R. Berenson, MD, Inc	West Hollywood	California	United States	90069
2	Winship Cancer Institute/Emory University	Atlanta	Georgia	United States	30322
3	Ohio State University Wexner Medical Center James Cancer Hospital	Columbus	Ohio	United States	43210
4	UPMC (University of Pittsburgh Medical Center) Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
5	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
6	Swedish Medical Center	Seattle	Washington	United States	98104
7	Froedtert Hospital & The Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Chinook Therapeutics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Nov 13, 2018
• Statistical Analysis Plan - Jul 18, 2019

More Information

Publications

• 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.

• Responsible Party: Chinook Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03340883
• Other Study ID Numbers: ADU-CL-16
• First Posted: Nov 14, 2017
• Last Update Posted: Apr 1, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell

Study Results

Participant Flow

Recruitment Details	Subject enrollment was stopped prematurely due to the sponsor's decision to terminate the study. Therefore, the study did not proceed to the Phase 2 portion of the study protocol. All reporting groups are for Phase 1 only.

Arm/Group Title	BION-1301 50 mg Q2W	BION-1301 150 mg Q2W	BION-1301 450 mg Q2W	BION-1301 1350 mg Q2W	BION-1301 2700 mg Q2W	BION-1301 1350 mg QW*8W->Q2W
Arm/Group Description	50 mg BION-1301 will be administered once every 2 weeks as an intravenous (IV) infusion.	150 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	450 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	2700 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered as an IV infusion once per week for up to 8 weeks, followed by dosing once every 2 weeks.
Period Title: Overall Study
STARTED	4	3	4	4	3	3
COMPLETED	4	3	4	4	3	3
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Phase 1 BION-1301
Arm/Group Description	BION-1301 will be administered once every 2 weeks as an intravenous (IV) infusion. BION-1301: a solution for intravenous (IV) administration, diluted and administered Q2W
Overall Participants	21
Age, Customized (Count of Participants)
<65 years	6 28.6%
>=65 years	15 71.4%
Sex: Female, Male (Count of Participants)
Female	9 42.9%
Male	12 57.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	20 95.2%
Unknown or Not Reported	1 4.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 9.5%
White	16 76.2%
More than one race	0 0%
Unknown or Not Reported	3 14.3%

Outcome Measures

1. Primary Outcome

Title	Safety (Phase 1)
Description	Number of patients reporting treatment-related adverse events that qualify as dose-limiting toxicities (DLTs) of BION-1301 as a single agent
Time Frame	28 days following first administration of BION-1301

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (all participants who received any amount of study drug) in the Phase 1 part of the study.

Arm/Group Title	BION-1301 50 mg Q2W	BION-1301 150 mg Q2W	BION-1301 450 mg Q2W	BION-1301 1350 mg Q2W	BION-1301 2700 mg Q2W	BION-1301 1350 mg QW*8W->Q2W
Arm/Group Description	50 mg BION-1301 will be administered once every 2 weeks as an intravenous (IV) infusion.	150 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	450 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	2700 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered as an IV infusion once per week for up to 8 weeks, followed by dosing once every 2 weeks.
Measure Participants	4	3	4	4	3	3
Count of Participants [Participants]	0 0%	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN

2. Primary Outcome

Title	Recommended Phase 2 Dose (Phase 1)
Description	Recommended Phase 2 Dose RP2D of BION-1301 when administered as a single-agent
Time Frame	Approximately 2 years

Outcome Measure Data

Analysis Population Description

Study was terminated early. No outcome measures were assessed.

Arm/Group Title	BION-1301 50 mg Q2W	BION-1301 150 mg Q2W	BION-1301 450 mg Q2W	BION-1301 1350 mg Q2W	BION-1301 2700 mg Q2W	BION-1301 1350 mg QW*8W->Q2W
Arm/Group Description	50 mg BION-1301 will be administered once every 2 weeks as an intravenous (IV) infusion.	150 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	450 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	2700 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered as an IV infusion once per week for up to 8 weeks, followed by dosing once every 2 weeks.
Measure Participants	0	0	0	0	0	0

3. Primary Outcome

Title	Biomarkers (Phase 1 and 2)
Description	Biomarkers such as soluble a proliferation inducing ligand (APRIL; TNFSF13); soluble B cell maturation antigen (BCMA; TNFRSF17)
Time Frame	Baseline and approximately 2 years

Outcome Measure Data

Analysis Population Description

Study was terminated early and Phase 2 did not enroll. BCMA was an exploratory endpoint and was not reported.

Arm/Group Title	BION-1301 50 mg Q2W	BION-1301 150 mg Q2W	BION-1301 450 mg Q2W	BION-1301 1350 mg Q2W	BION-1301 2700 mg Q2W	BION-1301 1350 mg QW*8W->Q2W
Arm/Group Description	50 mg BION-1301 will be administered once every 2 weeks as an intravenous (IV) infusion.	150 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	450 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	2700 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered as an IV infusion once per week for up to 8 weeks, followed by dosing once every 2 weeks.
Measure Participants	4	3	4	4	3	3
Free APRIL target engagement (AUEC1-15d)	1000	970	470	140	72	200

4. Primary Outcome

Title	Bioanalytical Measures (Phase 1 and Phase 2)
Description	Relative change in serum and urine M-protein levels defined as the maximum reduction from baseline
Time Frame	Baseline and approximately 2 years

Outcome Measure Data

Analysis Population Description

Some laboratory tests were not performed for some of the participants. Therefore, the number analyzed does not always match the overall number of participants analyzed. Study was terminated early and Phase 2 did not enroll.

Arm/Group Title	BION-1301 50 mg Q2W	BION-1301 150 mg Q2W	BION-1301 450 mg Q2W	BION-1301 1350 mg Q2W	BION-1301 2700 mg Q2W	BION-1301 1350 mg QW*8W->Q2W
Arm/Group Description	50 mg BION-1301 will be administered once every 2 weeks as an intravenous (IV) infusion.	150 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	450 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	2700 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered as an IV infusion once per week for up to 8 weeks, followed by dosing once every 2 weeks.
Measure Participants	4	3	4	4	3	3
Serum A/G Ratio (RATIO)	24.763	31.538	28.571	20.202
Serum Albumin (g/dL)	40.191	5.405	10.591	9.294	3.571	7.979
Serum Alpha-1 Globulin (g/dL)	18.698	30.556	29.710	24.138	16.129	20.000
Serum Alpha-2 Globulin (g/dL)	2.985	31.579	14.286	10.843	14.286	10.000
Serum Beta Globulin (g/dL)	33.636	3.125	0.542	22.472	8.571	2.609
Serum Gamma Globulin (g/dL)	13.920	96.552	25.926	23.441	0.627
Serum Immunoglobulin A (g/L)	1.615	66.667	36.174	30.536	23.077	23.077
Serum Immunoglobulin G (g/L)	25.274	25.000	25.016	20.125	0.352
Serum Immunoglobulin M (g/L)	27.273	28.571	40.000	61.364	64.148
Serum Kappa Light Chain, Free (mg/dL)	34.0000	5.9735	42.0349	72.4863	64.8649	47.9787
Serum Kappa LtChain,Free/LambdaLtChain,Free(RATIO)	53.919	50.000	100.000	60.000	100.000
Serum Lambda Light Chain, Free (mg/dL)	13.9651	26.3520	13.4372	26.9335	24.5619
Serum Monoclonal Protein Spike (g/dL)	13.1579	5.4670	27.2727
Serum Protein (g/dL)	8.14	3.06	3.03	6.74	3.05
Urine Albumin (mg/dL)	18.1818	54.7349
Urine Alpha-1 Globulin (mg/dL)	80.0000	71.7418
Urine Alpha-2 Globulin (mg/dL)	63.5621
Urine Beta Globulin (mg/dL)	19.4996	49.3411
Urine Gamma Globulin (mg/dL)	90.3185	100.0000	93.1735
Urine Monoclonal Protein Spike (%)	2.755	30.695	11.819
Urine Protein (mg/dL)	52.9665
Urine Protein, Calculated (mg/24hr)	9.1743	42.9298

5. Primary Outcome

Title	Safety Profile (Phase 2)
Description	BION-1301 safety profile based on incidence of TEAEs (treatment emergent adverse events), changes in safety parameters, and unacceptable toxicities
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

Study was terminated early and Phase 2 was not enrolled. Safety profile was not assessed.

Arm/Group Title	BION-1301 50 mg Q2W	BION-1301 150 mg Q2W	BION-1301 450 mg Q2W	BION-1301 1350 mg Q2W	BION-1301 2700 mg Q2W	BION-1301 1350 mg QW*8W->Q2W
Arm/Group Description	50 mg BION-1301 will be administered once every 2 weeks as an intravenous (IV) infusion.	150 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	450 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	2700 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered as an IV infusion once per week for up to 8 weeks, followed by dosing once every 2 weeks.
Measure Participants	0	0	0	0	0	0

6. Primary Outcome

Title	Response Rate (Phase 2)
Description	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)
Time Frame	Approximately 30 months

Outcome Measure Data

Analysis Population Description

Study was terminated early and Phase 2 was not enrolled. Objective response rate was not assessed.

Arm/Group Title	BION-1301 50 mg Q2W	BION-1301 150 mg Q2W	BION-1301 450 mg Q2W	BION-1301 1350 mg Q2W	BION-1301 2700 mg Q2W	BION-1301 1350 mg QW*8W->Q2W
Arm/Group Description	50 mg BION-1301 will be administered once every 2 weeks as an intravenous (IV) infusion.	150 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	450 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	2700 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered as an IV infusion once per week for up to 8 weeks, followed by dosing once every 2 weeks.
Measure Participants	0	0	0	0	0	0

7. Primary Outcome

Title	Progression-Free Survival (Phase 2)
Description	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
Time Frame	Approximately 30 months

Outcome Measure Data

Analysis Population Description

Study was terminated early and Phase 2 did not enroll. Progression-free survival was not assessed.

Arm/Group Title	BION-1301 50 mg Q2W	BION-1301 150 mg Q2W	BION-1301 450 mg Q2W	BION-1301 1350 mg Q2W	BION-1301 2700 mg Q2W	BION-1301 1350 mg QW*8W->Q2W
Arm/Group Description	50 mg BION-1301 will be administered once every 2 weeks as an intravenous (IV) infusion.	150 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	450 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	2700 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered as an IV infusion once per week for up to 8 weeks, followed by dosing once every 2 weeks.
Measure Participants	0	0	0	0	0	0

8. Primary Outcome

Title	Overall Survival (Phase 2)
Description	Overall survival (OS) defined as the time from first dose of study drug to date of death due to any cause
Time Frame	Approximately 30 months

Outcome Measure Data

Analysis Population Description

Study was terminated early and Phase 2 did not enroll. Overall survival was not assessed.

Arm/Group Title	BION-1301 50 mg Q2W	BION-1301 150 mg Q2W	BION-1301 450 mg Q2W	BION-1301 1350 mg Q2W	BION-1301 2700 mg Q2W	BION-1301 1350 mg QW*8W->Q2W
Arm/Group Description	50 mg BION-1301 will be administered once every 2 weeks as an intravenous (IV) infusion.	150 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	450 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	2700 mg BION-1301 will be administered once every 2 weeks as an IV infusion.	1350 mg BION-1301 will be administered as an IV infusion once per week for up to 8 weeks, followed by dosing once every 2 weeks.
Measure Participants	0	0	0	0	0	0

Adverse Events

Time Frame	From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 1 year from the date of randomization.
Arm/Group Title	BION-1301 50 mg Q2W		BION-1301 150 mg Q2W		BION-1301 450 mg Q2W		BION-1301 1350 mg Q2W		BION-1301 2700 mg Q2W		BION-1301 1350 mg QW*8W->Q2W
Arm/Group Description	50 mg BION-1301 will be administered once every 2 weeks as an intravenous (IV) infusion.		150 mg BION-1301 will be administered once every 2 weeks as an IV infusion.		450 mg BION-1301 will be administered once every 2 weeks as an IV infusion.		1350 mg BION-1301 will be administered once every 2 weeks as an IV infusion.		2700 mg BION-1301 will be administered once every 2 weeks as an IV infusion.		1350 mg BION-1301 will be administered as an IV infusion once per week for up to 8 weeks, followed by dosing once every 2 weeks.
All Cause Mortality
	BION-1301 50 mg Q2W		BION-1301 150 mg Q2W		BION-1301 450 mg Q2W		BION-1301 1350 mg Q2W		BION-1301 2700 mg Q2W		BION-1301 1350 mg QW*8W->Q2W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		2/3 (66.7%)		0/4 (0%)		2/4 (50%)		1/3 (33.3%)		1/3 (33.3%)
Serious Adverse Events
	BION-1301 50 mg Q2W		BION-1301 150 mg Q2W		BION-1301 450 mg Q2W		BION-1301 1350 mg Q2W		BION-1301 2700 mg Q2W		BION-1301 1350 mg QW*8W->Q2W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/4 (75%)		1/3 (33.3%)		1/4 (25%)		2/4 (50%)		0/3 (0%)		1/3 (33.3%)
Blood and lymphatic system disorders
Febrile neutropenia	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
General disorders
Asthenia	0/4 (0%)		0/3 (0%)		1/4 (25%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Sudden death	1/4 (25%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Disease progression	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Infections and infestations
Lung infection	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Staphylococcal sepsis	1/4 (25%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Injury, poisoning and procedural complications
Post procedural haemorrhage	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Metabolism and nutrition disorders
Hypercalcaemia	0/4 (0%)		1/3 (33.3%)		1/4 (25%)		0/4 (0%)		0/3 (0%)		1/3 (33.3%)
Musculoskeletal and connective tissue disorders
Compartment syndrome	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Renal and urinary disorders
Acute kidney injury	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Renal failure	0/4 (0%)		0/3 (0%)		1/4 (25%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Wheezing	1/4 (25%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	BION-1301 50 mg Q2W		BION-1301 150 mg Q2W		BION-1301 450 mg Q2W		BION-1301 1350 mg Q2W		BION-1301 2700 mg Q2W		BION-1301 1350 mg QW*8W->Q2W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		3/3 (100%)		4/4 (100%)		3/4 (75%)		2/3 (66.7%)		3/3 (100%)
Blood and lymphatic system disorders
Anaemia	1/4 (25%)		0/3 (0%)		1/4 (25%)		2/4 (50%)		0/3 (0%)		1/3 (33.3%)
Neutropenia	1/4 (25%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Thrombocytopenia	0/4 (0%)		0/3 (0%)		0/4 (0%)		2/4 (50%)		0/3 (0%)		0/3 (0%)
Leukopenia	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Lymphopenia	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Pancytopenia	0/4 (0%)		0/3 (0%)		1/4 (25%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Cardiac disorders
Sinus bradycardia	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Eye disorders
Diplopia	0/4 (0%)		1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Vision blurred	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Gastrointestinal disorders
Constipation	3/4 (75%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Diarrhoea	1/4 (25%)		0/3 (0%)		1/4 (25%)		0/4 (0%)		0/3 (0%)		1/3 (33.3%)
Nausea	1/4 (25%)		1/3 (33.3%)		0/4 (0%)		0/4 (0%)		1/3 (33.3%)		0/3 (0%)
Abdominal pain upper	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		1/3 (33.3%)
Abdominal pain	0/4 (0%)		0/3 (0%)		1/4 (25%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Dry mouth	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Stomatitis	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Vomiting	1/4 (25%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
General disorders
Fatigue	1/4 (25%)		0/3 (0%)		0/4 (0%)		3/4 (75%)		0/3 (0%)		0/3 (0%)
Pyrexia	1/4 (25%)		1/3 (33.3%)		0/4 (0%)		1/4 (25%)		1/3 (33.3%)		0/3 (0%)
Chills	0/4 (0%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		1/3 (33.3%)
Localised oedema	1/4 (25%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Non-cardiac chest pain	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Oedema peripheral	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Infections and infestations
Upper respiratory tract infection	1/4 (25%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Conjunctivitis	0/4 (0%)		1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Hordeolum	1/4 (25%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Pneumonia	0/4 (0%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		1/3 (33.3%)		0/3 (0%)
Rhinovirus infection	0/4 (0%)		1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Urinary tract infection	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Injury, poisoning and procedural complications
Contusion	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Foot fracture	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Rib fracture	0/4 (0%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		1/3 (33.3%)
Investigations
Blood creatinine increased	0/4 (0%)		0/3 (0%)		0/4 (0%)		2/4 (50%)		0/3 (0%)		0/3 (0%)
Activated partial thromboplastin time prolonged	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Blood fibrinogen decreased	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
International normalised ratio increased	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Metabolism and nutrition disorders
Hypercalcaemia	1/4 (25%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Decreased appetite	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		2/3 (66.7%)
Hyperuricaemia	1/4 (25%)		0/3 (0%)		0/4 (0%)		2/4 (50%)		0/3 (0%)		0/3 (0%)
Hypomagnesaemia	1/4 (25%)		1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		1/3 (33.3%)
Dehydration	1/4 (25%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Hyperkalaemia	0/4 (0%)		0/3 (0%)		0/4 (0%)		2/4 (50%)		0/3 (0%)		0/3 (0%)
Hyponatraemia	1/4 (25%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Hypermagnesaemia	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Hypoalbuminaemia	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Hypocalcaemia	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Hypokalaemia	1/4 (25%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/4 (0%)		1/3 (33.3%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		2/3 (66.7%)
Pain in extremity	0/4 (0%)		0/3 (0%)		0/4 (0%)		2/4 (50%)		1/3 (33.3%)		0/3 (0%)
Arthralgia	1/4 (25%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		1/3 (33.3%)
Myalgia	1/4 (25%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Neck pain	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		1/3 (33.3%)
Bone pain	1/4 (25%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Muscular weakness	1/4 (25%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Pain in jaw	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Osteopenia	0/4 (0%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		1/3 (33.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Head and neck cancer	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Nervous system disorders
Dysgeusia	0/4 (0%)		0/3 (0%)		2/4 (50%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Dizziness	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Muscle spasticity	1/4 (25%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Psychiatric disorders
Insomnia	0/4 (0%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		1/3 (33.3%)		1/3 (33.3%)
Renal and urinary disorders
Acute kidney injury	1/4 (25%)		1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Haematuria	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Incontinence	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Proteinuria	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Cough	0/4 (0%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		1/3 (33.3%)
Epistaxis	1/4 (25%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Sneezing	0/4 (0%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		1/3 (33.3%)
Skin and subcutaneous tissue disorders
Rash	0/4 (0%)		0/3 (0%)		1/4 (25%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Rash maculo-papular	1/4 (25%)		0/3 (0%)		0/4 (0%)		0/4 (0%)		0/3 (0%)		0/3 (0%)
Vascular disorders
Hypertension	0/4 (0%)		0/3 (0%)		0/4 (0%)		2/4 (50%)		1/3 (33.3%)		1/3 (33.3%)
Hypotension	1/4 (25%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)
Haematoma	0/4 (0%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		0/3 (0%)		0/3 (0%)

Limitations/Caveats

ADU-CL-16 was terminated early leading to a small number of Phase 1 subjects analyzed.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Disclosure restriction - study results first published in a joint multi-center paper unless (a) no multi-center publication, or (b) ≥18 months has passed since completion of the study. Thereafter, Investigator may publish provided that Investigator: (i) provides a copy of the publication to Aduro ≥ 60 days in advance of submission for publication; (ii) deletes Aduro Confidential Information (other than the Study results) and (iii) submission may be delayed up to 90 days to permit IP filings.