Phase 2, Multi-Center, Randomized, Open-Label Trial of BDC-1001 as a Single Agent and in Combination With Pertuzumab in Subjects With HER2-Positive Metastatic Breast Cancer Previously Treated With Trastuzumab Deruxtecan
Phase: PHASE2
Conditions: Metastatic Breast Cancer, HER2-positive Breast Cancer
Sponsor: Bolt Biotherapeutics, Inc.

Protocol BBI-20231001, Version 3.0, 01 August 2024 
BDC-1001 
 
 
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A PHASE 2, MULTI-CENTER, RANDOMIZED, OPEN-LABEL TRIAL OF BDC-1001 
AS SINGLE AGENT AND IN COMBINATION WITH PERTUZUMAB IN SUBJECTS 
WITH HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2–POSITIVE 
METASTATIC BREAST CANCER PREVIOUSLY TREATED WITH TRASTUZUMAB 
DERUXTECAN  
Investigational Product: 
INN Name: 
BDC-1001 
Trastuzumab imbotolimod 
Protocol Number: 
BBI-20231001 
IND #: 
 
ClinicalTrials.gov Identifier: 
NCT05954143 
EU CTIS Number: 
2023-506038-65-00 
Development Phase: 
Phase 2 
Sponsor: 
Bolt Biotherapeutics, Inc. 
900 Chesapeake Drive  
Redwood City, CA 94063 
 
 
Protocol Version: 
3.0 
01 August 2024 
 
 
Confidentiality Statement 
The information contained in this document, especially any unpublished data, is the property of Bolt 
Biotherapeutics, Inc. and therefore is provided to you in confidence as an Investigator, potential Investigator, or 
consultant for review by you, your staff, and an applicable Ethics Committee or Institutional Review Board.  It is 
understood that this information will not be disclosed to others without written authorization from Bolt 
Biotherapeutics except to the extent necessary to obtain informed consent from persons to whom the drug may be 
administered. 
 
 
Number: CLIN-00059    Approved Date: 01 Aug 2024

Protocol BBI-20231001, Version 3.0, 01 August 2024 
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PROTOCOL SIGNATURE PAGE – AUTHORS 
 
Protocol Title: 
A Phase 2, Multi-Center, Randomized, Open-Label Trial of 
BDC-1001 as Single Agent and in Combination with 
Pertuzumab in Subjects with Human Epidermal Growth 
Factor Receptor 2–Positive Metastatic Breast Cancer 
Previously Treated with Trastuzumab Deruxtecan 
Protocol Number: 
BBI-20231001 
Protocol Version:  
3.0 
01 August 2024 
 
This study protocol was subjected to critical review.  The information it contains is consistent 
with the current benefit/risk evaluation of the test preparation.  The study will be conducted in 
compliance with the protocol, The International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH), Good Clinical Practice (GCP), and any 
applicable regulatory requirements. 
This protocol is approved by: 
 
 
 
 
 
Refer to Veeva signature 
manifest at the end of the 
document 
 
 
 
 
Signature 
 
Date 
 
 
 
 
Refer to Veeva signature 
manifest at the end of the 
document 
 
 
 
 
Signature 
 
Date 
 
 
 
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Protocol BBI-20231001, Version 3.0, 01 August 2024 
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PROTOCOL SIGNATURE PAGE – INVESTIGATOR 
 
Protocol Title: 
A Phase 2, Multi-Center, Randomized, Open-Label Trial of 
BDC-1001 as Single Agent and in Combination with 
Pertuzumab in Subjects with Human Epidermal Growth 
Factor Receptor 2–Positive Metastatic Breast Cancer 
Previously Treated with Trastuzumab Deruxtecan 
Protocol Number: 
BBI-20231001 
Protocol Version: 
3.0  
01 August 2024 
 
I confirm that I have read and understood this protocol and agree to conduct the trial as outlined 
in the protocol and other information supplied to me.  I agree to conduct the trial in accordance 
with the Declaration of Helsinki and its amendments, Good Clinical Practice (GCP) guidelines 
established by the International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH), and applicable local legal and regulatory requirements.  
Furthermore, I confirm herewith that the Sponsor is allowed to enter and utilize my professional 
contact details and function in an electronic database for internal purposes only. 
The current version of the protocol has been reviewed and approved. 
 
 
  
Principal Investigator’s Signature 
 Date 
 
 
  
Print Principal Investigator’s Name 
  
 
 
 
 
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Protocol BBI-20231001, Version 3.0, 01 August 2024 
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TABLE OF CONTENTS 
PROTOCOL SIGNATURE PAGE – Authors ................................................................................2 
PROTOCOL SIGNATURE PAGE – Investigator ..........................................................................3 
LIST OF APPENDICES ..................................................................................................................8 
LIST OF TABLES ...........................................................................................................................9 
LIST OF FIGURES .........................................................................................................................9 
SYNOPSIS .....................................................................................................................................10 
SCHEDULE OF ASSESSMENTS ................................................................................................17 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ..................................................22 
DEFINITION OF TERMS ............................................................................................................26 
1. 
INTRODUCTION ................................................................................................................27 
1.1. 
Disease Background...........................................................................................................27 
1.2. 
Study Treatment Background ............................................................................................27 
1.2.1. 
BDC-1001 Background ...............................................................................................27 
1.2.1.1. 
Nonclinical Studies ................................................................................................29 
1.2.1.2. 
Clinical Studies ......................................................................................................30 
1.2.2. 
Pertuzumab Background ..............................................................................................31 
1.3. 
Study Rationale ..................................................................................................................32 
1.4. 
Risk/Benefit Assessment ...................................................................................................34 
2. 
STUDY OBJECTIVES ........................................................................................................36 
2.1. 
Objectives and Endpoints ..................................................................................................36 
3. 
INVESTIGATIONAL PLAN ..............................................................................................37 
3.1. 
Overall Study Design .........................................................................................................37 
3.1.1. 
Study Oversight ...........................................................................................................38 
3.1.2. 
Number of Subjects......................................................................................................38 
3.1.3. 
Duration of Treatment..................................................................................................38 
3.1.4. 
Duration of Study .........................................................................................................39 
3.2. 
Rationale for Study Design, Dose Selection, and Study Population .................................39 
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3.2.1. 
Rationale for Study Design ..........................................................................................39 
3.2.2. 
Rationale for Selection of BDC-1001 Recommended Dose........................................39 
4. 
SELECTION OF STUDY POPULATION ..........................................................................42 
4.1. 
Inclusion Criteria ...............................................................................................................42 
4.2. 
Exclusion Criteria ..............................................................................................................43 
4.3. 
Subject Discontinuation .....................................................................................................45 
4.3.1. 
Removal of Subjects from the Treatment or Study .....................................................45 
4.3.2. 
Lost to Follow-Up ........................................................................................................46 
4.3.3. 
Replacement of Subjects ..............................................................................................46 
4.4. 
Method of Assigning Subjects ...........................................................................................46 
4.5. 
Randomization Procedures ................................................................................................46 
4.5.1. 
Blinding........................................................................................................................46 
5. 
ENROLLMENT PROCEDURES ........................................................................................47 
5.1. 
Method of Assigning Subjects ...........................................................................................47 
5.1.1. 
Description of BDC-1001 ............................................................................................47 
5.1.2. 
Description of Pertuzumab ..........................................................................................47 
5.1.3. 
Preparation/Handling/Storage/Accountability .............................................................47 
5.1.3.1. 
Labelling and Packaging ........................................................................................47 
5.1.3.2. 
Storage and Stability ..............................................................................................47 
5.1.3.3. 
Acquisition and Accountability .............................................................................47 
5.1.3.4. 
Return of BDC-1001 and Pertuzumab ...................................................................47 
5.2. 
Dosing and Administration ................................................................................................48 
5.2.1. 
Premedication ..............................................................................................................48 
5.2.2. 
BDC-1001 Administration ...........................................................................................48 
5.2.3. 
Pertuzumab Administration .........................................................................................48 
5.2.4. 
Dose Modifications ......................................................................................................49 
5.2.4.1. 
Dose Interruptions ..................................................................................................49 
5.2.4.2. 
BDC-1001 Dose Reductions ..................................................................................50 
5.2.4.3. 
Pertuzumab Dose Reductions ................................................................................50 
5.3. 
Management of Specific Safety Concerns .........................................................................50 
5.3.1. 
Infusion-Related Reactions ..........................................................................................50 
5.3.2. 
Immune-Related Events ...............................................................................................50 
5.3.3. 
Cardiac Toxicity...........................................................................................................52 
5.3.4. 
Cytokine Release Syndrome ........................................................................................52 
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5.4. 
Prior and Concomitant Medications ..................................................................................53 
5.4.1. 
Recording of Use of Concomitant Medications ...........................................................53 
5.4.2. 
Prohibited Concomitant Therapy .................................................................................53 
5.4.2.1. 
Anti-Cancer Therapy .............................................................................................53 
5.4.2.2. 
Immunomodulatory Therapy .................................................................................53 
5.5. 
Study Treatment Compliance ............................................................................................54 
5.5.1. 
Concomitant Medications ............................................................................................54 
5.6. 
Discontinuation of Study Treatment / Withdrawal from Study .........................................54 
6. 
STUDY ASSESSMENTS AND PROCEDURES ...............................................................55 
6.1. 
Screening Period and Enrollment Description ...................................................................55 
6.2. 
Informed Consent...............................................................................................................55 
6.3. 
Eligibility Criteria Review .................................................................................................55 
6.4. 
Physical Examination, Weight, and Height .......................................................................56 
6.5. 
Study Treatment Administration........................................................................................56 
6.6. 
Medical History and Demographics ..................................................................................56 
6.7. 
ECOG Performance Status ................................................................................................56 
6.8. 
Vital Signs ..........................................................................................................................57 
6.9. 
Electrocardiograms ............................................................................................................57 
6.10. Echocardiograms or Multi-gated Acquisition Scans .........................................................58 
6.11. Pulse Oximetry...................................................................................................................58 
6.12. Prior and Concomitant Medications ..................................................................................58 
6.13. Adverse Events ..................................................................................................................58 
6.14. Viral Screening ..................................................................................................................58 
6.14.1. 
Hepatitis B Screening ..................................................................................................58 
6.14.2. 
Hepatitis C Screening ..................................................................................................58 
6.14.3. 
HIV Screening .............................................................................................................59 
6.15. Pregnancy Testing ..............................................................................................................59 
6.15.1. 
Pregnancy Testing ........................................................................................................59 
6.15.2. 
Pregnancy On-Study ....................................................................................................59 
6.16. Clinical Laboratory Safety Assessments ...........................................................................59 
6.16.1. 
Chemistry .....................................................................................................................60 
6.16.2. 
Hematology ..................................................................................................................60 
6.16.3. 
Coagulation ..................................................................................................................60 
6.16.4. 
Urinalysis .....................................................................................................................60 
6.17. Thyroid Function Testing ..................................................................................................60 
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6.18. Serum Tumor Markers .......................................................................................................60 
6.19. Pharmacokinetics ...............................................................................................................61 
6.20. Immunogenicity (Anti-BDC-1001 Antibodies) .................................................................61 
6.21. Exploratory Biomarker Assessments .................................................................................61 
6.22. Tumor Specimens ..............................................................................................................61 
6.22.1. 
Fresh Tissue Biopsy .....................................................................................................61 
6.22.2. 
Archival Tissue ............................................................................................................62 
6.23. Tumor Assessments ...........................................................................................................62 
6.24. Survival Information ..........................................................................................................63 
6.25. Procedures at End of Treatment and Follow-Up ...............................................................63 
6.25.1. 
End of Treatment .........................................................................................................63 
6.25.2. 
Safety Follow-Up .........................................................................................................64 
6.25.3. 
Long-Term Follow-Up / End of Study ........................................................................64 
6.25.4. 
Treatment after the End of Study .................................................................................64 
7. 
Adverse Events .....................................................................................................................65 
7.1. 
Adverse Event Definitions .................................................................................................65 
7.1.1. 
Adverse Event ..............................................................................................................65 
7.1.2. 
Serious Adverse Event .................................................................................................65 
7.2. 
Detecting and Reporting Adverse Events and Serious Adverse Events ............................66 
7.2.1. 
Grading and Intensity ...................................................................................................67 
7.2.2. 
Relationship to Study Treatment / Causality ...............................................................68 
7.2.3. 
Outcome and Action Taken .........................................................................................68 
7.2.4. 
Serious Adverse Event Reporting Requirements .........................................................68 
7.3. 
Follow-up of Adverse Events and Serious Adverse Events ..............................................68 
7.4. 
Pregnancy Reporting ..........................................................................................................69 
7.5. 
Overdose Reporting ...........................................................................................................69 
8. 
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN .......................................70 
8.1. 
Endpoints ...........................................................................................................................70 
8.2. 
Determination of Sample Size ...........................................................................................70 
8.3. 
Analysis Populations ..........................................................................................................70 
8.3.1. 
Safety Analysis Set ......................................................................................................70 
8.3.2. 
Full Analysis Set (FAS) ...............................................................................................70 
8.3.3. 
Pharmacokinetic Analysis Set (PKAS) ........................................................................70 
8.3.4. 
Pharmacodynamic Analysis Set (PDAS) .....................................................................71 
8.4. 
Statistical Methods .............................................................................................................71 
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8.4.1. 
Demographics and Baseline Characteristics ................................................................71 
8.4.2. 
Prior and Concomitant Medications ............................................................................71 
8.4.4. 
General Principles ........................................................................................................71 
8.4.5. 
Safety Analyses ............................................................................................................71 
8.4.5.1. 
Monitoring of Safety Data .....................................................................................72 
8.4.6. 
Pharmacokinetic and Pharmacodynamic Analyses .....................................................74 
8.4.7. 
Anti-Tumor Activity Analyses ....................................................................................74 
8.4.8. 
Biomarker Analysis .....................................................................................................75 
8.4.9. 
Immunogenicity Analysis ............................................................................................75 
9. 
Study Administration ...........................................................................................................76 
9.1. 
Ethical Conduct of Study ...................................................................................................76 
9.1.1. 
Approval by Independent Ethics Committee or Institutional Review Board ..............76 
9.1.2. 
Subject Informed Consent............................................................................................76 
9.1.3. 
Investigator Reporting Requirements ..........................................................................77 
9.1.4. 
Sponsor Safety Reporting to Regulatory Authorities / Investigator Sites ...................77 
9.1.5. 
Serious Adverse Event Notification to the Institutional Review Board/ 
Independent Ethics Committee ....................................................................................77 
9.1.6. 
Confidentiality .............................................................................................................77 
9.2. 
Regulatory: Data Quality Control and Quality Assurance ................................................78 
9.2.1. 
Compliance with Laws and Regulations......................................................................78 
9.2.2. 
Study Monitoring and Data Collection ........................................................................78 
9.2.3. 
Audit and Inspection ....................................................................................................79 
9.2.4. 
Protocol Adherence ......................................................................................................79 
9.2.5. 
Protocol Deviations ......................................................................................................79 
9.2.6. 
Records Retention ........................................................................................................80 
9.2.7. 
Investigator Reporting Policy ......................................................................................80 
9.3. 
Termination ........................................................................................................................80 
10. 
REFERENCES .....................................................................................................................81 
11. 
APPENDICES ......................................................................................................................84 
LIST OF APPENDICES 
Appendix A: 
Infusion Reaction Guideline ............................................................................84 
Appendix B: 
Management of Cytokine Release Syndrome ..................................................85 
Appendix C: 
RECIST v1.1 Criteria for Tumor Response .....................................................87 
Appendix D: 
iRECIST Criteria for Tumor Response ............................................................90 
Appendix E: 
Statistical Consideration for Defining Date of iRECIST PD...........................91 
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Appendix F: 
Summary of Changes from Version 2.0 to 3.0 ................................................92 
LIST OF TABLES 
Table 1: 
Overview of Schedule of Assessments ............................................................17 
Table 2: 
Overview of Schedule of Assessments – Maintenance Phase - Q2W 
Dosing ..............................................................................................................21 
Table 3: 
Objectives and Endpoints ................................................................................36 
Table 4: 
BDC-1001 Dose Interruption and Resumption Parameters .............................49 
Table 5: 
Dose Modifications Guidelines for BDC-1001 and Pertuzumab ....................51 
Table 6: 
Management of LVEF Changes (Based on Absolute Changes) ......................52 
Table 7: 
ECOG Performance Status ..............................................................................56 
Table 8: 
Timing of Vital Signs and ECG Collections....................................................57 
Table 9: 
NCI CTCAE v5.0 Definitions of Severity for Adverse Reactions ..................67 
Table 10: 
Bayesian Toxicity Monitoring Safety Stopping Rules ....................................73 
Table 11: 
RECIST v1.1 Criteria for Tumor Response .....................................................87 
Table 12: 
RECIST v1.1 Overall Response Criteria .........................................................88 
Table 13: 
Best Overall Response When Confirmation of CR and PR Required .............89 
Table 14: 
iRECIST Criteria for Tumor Response ............................................................90 
Table 15: 
iRECIST Guidelines for Progression Evaluation ............................................90 
LIST OF FIGURES 
Figure 1: 
Schematic Representation of BDC-1001 .........................................................28 
Figure 2: 
Proposed Mechanism of Action for BDC-1001...............................................29 
Figure 3: 
BDC-1001.S + Pertuzumab Augment Anti-Tumor Efficacy in JIMT-1 
Model ...............................................................................................................30 
Figure 4: 
Study Schema...................................................................................................38 
 
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SYNOPSIS 
SPONSOR/COMPANY:  
Bolt Biotherapeutics, Inc. 
PROTOCOL:  
Title: A Phase 2, Multi-Center, Randomized, Open-Label Trial of BDC-1001 as Single Agent and in Combination with 
Pertuzumab in Subjects with Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer Previously 
Treated with Trastuzumab Deruxtecan 
Number: BBI-20231001 
Phase: 2 
Investigational Medicinal Product: BDC-1001 (trastuzumab imbotolimod) 
STUDY SITES:  
Approximately 30 institutions across North America and the European Union were initially planned for participation in 
this study.   
NUMBER OF SUBJECTS PLANNED: 
Approximately 66 evaluable subjects 
OBJECTIVES AND ENDPOINTS: 
The objectives and endpoints to be evaluated in the study are as follows: 
Primary Objectives 
Primary Endpoints 
• Efficacy: To evaluate the preliminary anti-tumor 
activity of BDC-1001 as a single agent and in 
combination with pertuzumab in subjects with 
previously treated HER2+ MBC 
• ORR according to RECIST v1.1  
Secondary Objectives 
Secondary Endpoints 
• Efficacy: To evaluate the preliminary anti-tumor 
activity of BDC-1001 as a single agent and in 
combination with pertuzumab in subjects with 
previously treated HER2+ MBC 
• DOR, DCR, PFS, OS 
• Safety: To determine the safety and tolerability 
of BDC-1001 as a single agent and in 
combination with pertuzumab in subjects with 
previously treated HER2+ MBC 
• Incidence of treatment-emergent AEs and SAEs graded 
according to NCI CTCAE v5.0 
• Changes from baseline in vital signs, laboratory values, 
and ECGs 
• PK: To evaluate the exposure profile of BDC-
1001 as a single agent and in combination with 
pertuzumab in subjects with previously treated 
HER2+ MBC 
• Cmin and Cmax values will be obtained throughout the study 
and compared to the PK data from the Phase 1 single 
agent BDC-1001 study utilizing a population approach 
• ADA: To evaluate the immunogenicity of 
BDC-1001 as a single agent and in combination 
with pertuzumab in subjects with previously 
treated HER2+ MBC  
• Incidence of ADAs 
Exploratory Objectives 
Exploratory Endpoints 
• To explore potential baseline biomarkers in 
blood and tumor tissue associated with efficacy 
or safety of BDC-1001 as a single agent and in 
• Evaluation of BDC-1001 activity in the context of 
additional exploratory predictive and/or prognostic 
biomarkers related to tumor and immune biology by such 
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combination with pertuzumab in subjects with 
HER2+ MBC 
methods as gene expression profiling, mutational, protein 
and tissue image analysis 
• To evaluate exploratory pharmacodynamic 
biomarkers in blood and tumor and their 
association with biological activity, efficacy or 
safety of BDC-1001 as a single agent and in 
combination with pertuzumab in subjects with 
HER2+ MBC 
• Changes in TLR7/8 pathway activation, myeloid and 
T cell content, and activation status by such methods as 
gene expression profiling, protein, and tissue image 
analysis. 
• Evaluation of changes in additional exploratory 
biomarkers in tumor tissue and blood related to tumor and 
immune biology by such methods as gene expression 
profiling, mutational, protein and tissue image analysis 
Abbreviations: ADA = anti-BDC-1001 antibody; AE = adverse event; Cmax = maximum (or peak) serum concentration; Cmin = 
minimum (or trough) serum concentration; CTCAE = Common Terminology Criteria for Adverse Events; DCR = disease control rate; 
DOR = duration of response; ECG = electrocardiogram; HER2+ = human epidermal growth factor receptor 2-positiveMBC = 
metastatic breast cancer; NCI = National Cancer Institute; ORR = objective response rate; OS = overall survival; PFS = progression-
free survival; PK = pharmacokinetics; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; SAE = serious 
adverse event; TLR = toll-like receptor 
STUDY DESIGN/METHODOLOGY: 
This is an open label, Phase 2 study to evaluate preliminary anti-tumor activity, safety, tolerability, pharmacokinetics 
(PK), pharmacodynamics, and immunogenicity of BDC-1001 administered as a single agent and in combination with 
pertuzumab in subjects with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer 
(MBC) previously treated with trastuzumab deruxtecan (ENHERTU®). 
Eligible subjects will be randomly assigned in a 1:1 ratio to receive BDC-1001 as a single agent or BDC-1001 in 
combination with pertuzumab.  Within each treatment arm, a Simon 2-stage design will be applied for enrollment (see 
Section 8.2). 
Subjects will receive study treatment (ie, BDC-1001 or BDC-1001 in combination with pertuzumab) as described in 
Section 5.2.  To ensure subject safety, dosing of the first 3 subjects enrolled in the combination treatment arm will 
receive study treatment staggered by a minimum of 48 hours, and these subjects will be observed for at least 6 hours 
following the first dose of study treatment.  Any subject with acute changes in vital signs will be observed until the 
events have resolved or are stabilized. 
All subjects in both treatment arms will be monitored for adverse events (AEs) and serious adverse events (SAEs) 
(Section 8.4.5.1).  Study data will be provided to the Safety Review Committee (SRC) for ongoing safety monitoring 
and detection of potential safety concerns (Section 3.1.1). 
Subjects will return to the site for study assessments at the visits listed in the Schedule of Assessments.  In the event of 
study treatment discontinuation, subjects will be asked to complete an End of Treatment (EOT; Section 6.25.1) visit 
14 days (± 7 days) after the date of the last study treatment, and then return for a Safety Follow-Up (SFU; 
Section 6.25.2) visit 28 days (+7 days) after the last study treatment.  Subjects who discontinue treatment will have long-
term follow-up (LTFU; Section 6.25.3) every 12 weeks (± 14 days) for up to 2 years after the last study treatment. 
As of Protocol Version 3.0 (01 Aug 2024), any subject(s) still receiving study treatment (BDC-1001) will transition to 
the Maintenance Phase.  
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DURATION OF STUDY:  
The planned overall study duration is approximately 4 years.  
DURATION OF SUBJECT PARTICIPATION:  
Screening: Up to 28 days before Cycle 1 Day 1 (C1D1) 
Treatment duration: After C1D1 for a median duration of approximately 12 months. All subjects will be treated until 
disease progression, unacceptable toxicity, or withdrawal for any reason.  
As of protocol Version 3.0 (01 Aug 2024), any subject(s) still receiving study treatment (BDC-1001) will transition to 
the Maintenance Phase.  
Eligibility Criteria: 
Inclusion Criteria (Section 4.1): 
A subject must meet all of the following to be included in this study: 
1. Be able to understand and sign the informed consent form 
2. Be age 18 years or older at the time of informed consent 
3. All subjects must agree to have a biopsy prior to enrollment.  If, in the judgement of the Investigator, a biopsy 
is not safely accessible or clinically feasible an archival tumor tissue must be submitted in lieu of a freshly 
collected specimen 
4. Histologically confirmed adenocarcinoma of the breast that is HER2+ (per 2018 ASCO/CAP HER2 testing 
guidelines) by Clinical Laboratory Improvement Amendments (CLIA) certified laboratory assessment 
5. Have received 2 or more prior lines of anti-human epidermal growth factor receptor 2 (HER2)-directed 
therapies, at least 1 of them is in the metastatic setting and 1 of the prior therapies needs to be trastuzumab 
deruxtecan (ENHERTU®).  Prior neo-adjuvant or adjuvant therapy that resulted in relapse within 12 months of 
completion of therapy will be considered a line of treatment for metastatic disease 
6. Have experienced disease progression on or been otherwise unsuitable for (eg, did not tolerate) the most recent 
therapy 
7. Have measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 
(RECIST v1.1) criteria 
8. Have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 
9. Have expected life expectancy of greater than 12 weeks per the Investigator 
10. Adequate organ function defined as follows: 
a. 
Hematology: 
i. Absolute neutrophil count ≥ 1500 cells/mm3 
ii. Platelet count ≥ 75,000 cells/mm3  
iii. Hemoglobin ≥ 9 g/dL (and without transfusion within 7 days) 
b. Renal: 
i. Creatinine clearance ≥ 30 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate 
estimation:  
(140 – age) × (weight in kg) × (0.85 if female)  
72 × (serum creatinine in mg/dL) 
c. 
Coagulation: 
i. International normalized ratio (INR) and prothrombin time (PT) ≤ 1.5 × upper limit of normal (ULN) 
unless receiving anticoagulation therapy  
ii. Activated partial thromboplastin time (aPTT) only needs to be assessed if evaluated per standard of 
care.  If evaluated, aPTT ≤ 1.5 × ULN, unless undergoing anticoagulation therapy 
d. Hepatic: 
i. 
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN (or ≤ 5 × ULN in 
subjects with known hepatic metastases) 
ii. 
Total bilirubin ≤ 1.5 × ULN (isolated value > 1.5 × ULN is acceptable if direct bilirubin is <35%) 
11. Women of childbearing potential should agree not to donate eggs and must use a highly effective contraceptive 
measure (a method that can achieve a failure rate of less than 1% per year) during treatment and until 7 months 
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after the end treatment.  Highly effective, alternative non-hormonal contraceptive measures are preferred, 
include the following: 
a. 
Intrauterine device  
b. Vasectomized partner  
c. 
Sexual abstinence  
d. Bilateral tubal occlusion  
12. Potent men that are partners of women of childbearing potential must be willing to use condoms in 
combination with a second highly effective method of female contraception (as above) during the study and 
agree not to donate sperm from Screening through 7 months after completion of study.  A male partner will be 
considered as potent unless surgically sterilized (with documentation of sterility).  
Exclusion Criteria (Section 4.2): 
A subject must not meet any of the following criteria to be eligible for this study: 
1. Central nervous system metastases with the exception of disease that is asymptomatic, clinically stable (without 
evidence of progression for at least 4 weeks confirmed by imaging during study Screening), and has not required 
steroids for at least 28 days before starting study treatment 
2. Cardiac disease including the following: 
a. 
Congestive heart failure (New York Heart Association classes II–IV) 
b. Left ventricular ejection fraction (LVEF) < 50% by echocardiogram (ECHO) or multi-gated acquisition 
(MUGA) scan 
c. 
QT corrected - Fridericia's correction formula (QTcF) prolongation of > 480 milliseconds (ms) based on a 
12-lead electrocardiogram (ECG)  
d. Serious or uncontrolled cardiac arrhythmia within 6 months before starting study treatment 
e. 
Myocardial infarction, unstable angina pectoris, or coronary angioplasty, stenting, or surgery within 6 months 
before starting study treatment 
f. 
Serious or uncontrolled hypertension (≥ 180 mmHg systolic or ≥ 120 mmHg diastolic) within 6 months before 
starting study treatment 
g. Pericarditis or pericardial effusion that is symptomatic within 6 months before starting study treatment 
3. Pulmonary disease including idiopathic pulmonary fibrosis, interstitial lung disease, pneumonitis requiring steroids, 
or symptomatic pleural effusion within 6 months before starting study treatment OR ongoing requirement for 
supplemental oxygen 
4. Hepatic disease resulting in symptomatic ascites, encephalopathy, coagulopathy, esophageal/gastric varices, or 
persistent jaundice 
5. Arterial thrombotic event, stroke, or transient ischemia attack within 6 months before starting study treatment 
6. Bleeding diathesis or uncontrolled bleeding within 7 days before starting study treatment 
7. Bone marrow transplant or solid organ transplant 
8. Infection including the following:  
a. 
Infection requiring systemic therapy within 7 days before starting study treatment 
b. Active human immunodeficiency virus (HIV) as defined by the protocol (Section  6.14.3) 
c. 
Positive hepatitis B surface antigen test at Screening or within 3 months of starting study treatment, a subject 
whose hepatitis B surface antigen (HBsAg) is negative and hepatitis B core antibody (HBcAb) is positive may 
be enrolled if a hepatitis B virus (HBV) DNA test is negative and either the subject is treated with potent 
antiviral therapy or is retested for HBsAg and HBV DNA every month 
d. Positive hepatitis C antibody test and confirmatory ribonucleic acid (RNA) test at Screening or within 3 months 
of starting study treatment.  Exceptions include subjects that (1) have hepatitis C virus (HCV) viral load below 
the assay limit-of-quantitation and (2) completed curative antiviral therapy or are compliant with ongoing 
antiviral therapy 
9. Autoimmune disease requiring systemic disease-modifying or immunosuppressive therapy within 2 years before 
starting study treatment.  Exceptions include disease managed with only replacement therapies (eg, thyroxine, etc.) 
10. Malignancy within 2 years before starting study treatment other than the disease under study.  Exceptions include 
indolent or definitively treated disease not expected to require treatment during the study, affect the safety of 
subjects, or affect the endpoints of the trial 
Number: CLIN-00059    Approved Date: 01 Aug 2024

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11. Any medical condition requiring corticosteroids (> 10 mg daily oral prednisone or equivalent) or other systemic 
immunosuppressive therapy within 28 days before starting study treatment.  Exceptions include inhaled or topical 
steroids 
12. Residual toxicity from previous treatment including the following: 
a. 
Toxicity related to prior treatment not resolved to Grade ≤ 1 
Exceptions to the above criteria include toxicities that do not pose a risk to vital organ systems (eg, alopecia, 
etc.) or toxicities that are stable as managed by replacement therapies (eg, hypothyroidism, etc.) 
13. Prior anticancer therapies including: 
a. 
Small molecule toll-like receptor (TLR)7/8 agonist or TLR7/8 agonist that has been conjugated to tumor-
targeting antibody such as immune stimulating antibody conjugates (ISAC) within 12 months before starting 
study treatment 
b. An investigational agent or anticancer therapy within 28 days before starting study treatment or within 
5 estimated elimination half-lives, whichever is shorter.  Gonadotropin-releasing hormone agonists for ovarian 
suppression in premenopausal women are permitted 
14. History of severe hypersensitivity to any ingredient of BDC-1001 or pertuzumab 
15. Received live/attenuated virus vaccine within 28 days before starting study treatment 
16. Major surgery within 28 days of starting study treatment 
17. Radiation therapy within 2 weeks of C1D1 
18. Actively enrolled in another clinical study, unless it is an observational (noninterventional) clinical study or the 
follow-up component of an interventional study 
19. Subject is a lactating mother or pregnant as confirmed by pregnancy tests within 48 hours prior to start of study 
treatment 
20. Subject is unwilling or unable to follow protocol requirements 
21. Recurrent ascites requiring routine intervention >Q3 months 
22. Any condition that, in the opinion of the Investigator, would interfere with evaluation of BDC-1001 and pertuzumab 
or interpretation of the subject’s safety or study results 
TREATMENT PROCEDURES: 
Investigational Product: 
BDC-1001:  
The BDC-1001 dosage form is a sterile lyophilized cake/powder provided in a sterile glass vial (25 mg/mL, 10 mL fill, 
250 mg/vial).  The lyophilized powder will be reconstituted with sterile water for injection. 
Pertuzumab: 
The pertuzumab dosage form is a sterile, clear to slightly opalescent, colorless to pale brown liquid for intravenous (IV) 
infusion.  Each single-dose vial contains 420 mg of pertuzumab (14.0 mL/vial) at a concentration of 30 mg/mL in 
20 mM L-histidine acetate, 120 mM sucrose, and 0.02% polysorbate 20 at pH 6.0.  
 
Mode of Administration and Dosing: 
Premedication: 
All subjects should be premedicated prior to administration of BDC-1001 for potential infusion-related reactions (IRRs) 
with paracetamol and diphenhydramine (eg, 1000 mg paracetamol, 50 mg diphenhydramine) or according to institutional 
standards.  
On dosing days when pertuzumab is administered without BDC-1001, premedication for pertuzumab is only required if 
a subject experiences IRR during the previous dose.   
Corticosteroids and other immunomodulators remain excluded for study treatment infusions. 
BDC-1001 Administration: 
BDC-1001 will be administered every 2 weeks (q2w) at a dose of 20 mg/kg as an intravenous (IV) infusion over 
60 minutes (± 15 minutes).  BDC-1001 will be administered before pertuzumab on days that both BDC-1001 and 
pertuzumab are administered. 
Pertuzumab Administration: 
Number: CLIN-00059    Approved Date: 01 Aug 2024

Protocol BBI-20231001, Version 3.0, 01 August 2024 
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Pertuzumab will be administered as an IV infusion according to the package insert (ie, initial dose of 840 mg over 
60 minutes followed every 3 weeks by a dose of 420 mg over 30 to 60 minutes).  On days that both BDC-1001 and 
pertuzumab are administered, pertuzumab will be administered 30 to 60 minutes after the end of BDC-1001 infusion. 
 
Duration of Treatment: 
All subjects will be treated until disease progression, unacceptable toxicity, or withdrawal for any reason. 
Following progressive disease (PD) according to RECIST v1.1, treatment beyond disease progression will be allowed 
with the approval of the Sponsor, provided the subject is clinically stable.  Clinically stable is defined as follows:  
1. Subject is without worsening symptoms attributable to disease progression,  
2. Subject maintains ECOG status, and  
3. Subject tolerates study treatment (ie, no related SAE or Grade ≥ 3 AE that requires study drug discontinuation) per 
Investigator clinical judgement.  
Subject with confirmed PD (using the scan at first PD as the new baseline) will be discontinued from study treatment. 
 
Maintenance Phase:  
As of this protocol Version 3.0 (01 Aug 2024), any subjects still receiving study treatment (BDC-1001) will transition to 
the Maintenance Phase and are to be followed as described in Table 2.  Subjects remaining on study treatment will 
continue to receive the study drug until a criterion for discontinuation has been met (see Section 4.3).  Subjects are to 
undergo periodic safety assessments; the nature and frequency of these assessments are to be performed per local 
standard of care.  It is the Investigator’s responsibility to ensure that subject visits occur frequently enough and adequate 
assessments are performed to ensure subject safety.  
The study clinical database will be closed after the last subject remaining on treatment enters the Maintenance Phase.  
All data collected prior to implementation of the Maintenance Phase will be reported in a clinical study report.  
STUDY ASSESSMENTS: 
Study assessments will be conducted as outlined in the Schedule of Assessments. 
STATISTICAL ANALYSIS: 
Analysis Sets: 
The analysis sets are defined as follows: 
Safety Analysis Set is defined as enrolled subjects who receive at least 1 dose of BDC-1001 with or without pertuzumab.  
The Safety Analysis Set will be used primarily for the analysis of safety data. 
Full Analysis Set (FAS) will be used primarily for the analysis of tumor response and other anti-tumor activity-related 
data.  The FAS will include subjects who meet the following criteria: 
• Receive at least 1 dose of BDC-1001 with or without pertuzumab 
• Have 1 or more measurable lesion(s) at baseline and at least 1 postbaseline evaluable scan as assessed using RECIST 
v1.1 criteria.  
Pharmacokinetic Analysis Set (PKAS) will include subjects who meet the following criteria: 
• Receive any dose of BDC-1001 with or without pertuzumab 
• Have 1 or more post-infusion PK datapoint 
Pharmacodynamic Analysis Set (PDAS) will include subjects who meet the following criteria: 
• Receive any dose of BDC-1001 with or without pertuzumab 
• Have 1 or more sets of biomarker data  
Sample Size: 
Approximately 66 subjects will be randomized 1:1 to either the BDC-1001 monotherapy arm or the BDC-1001 plus 
pertuzumab arm.  Within each arm, a Simon 2-stage design will be used to evaluate objective response rate (ORR).  It is 
assumed under the null hypothesis, that objective response rate (ORR) will be ≤ 20% (not considered clinically 
compelling) for both arms.  Based on the probability of accepting the poor drug (one-sided alpha level) at 5%, 80% 
power, P0 and P1 at 20% and 40% respectively, 18 evaluable subjects will be enrolled into the first stage.  If at least 5 
objective responses are observed in an arm, the study will continue to enroll a total of 33 evaluable subjects to that arm.  
Number: CLIN-00059    Approved Date: 01 Aug 2024

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The null hypothesis will be rejected if at least 11 objective responses are observed out of the 33 evaluable subjects in an 
arm. 
Methodology: 
Detailed methodology for summary and statistical analyses of the data collected in this study will be documented in a 
Statistical Analysis Plan. 
Safety Analysis: 
Safety will be assessed through summaries of AEs, SAEs, changes in laboratory test results, changes in vital signs and 
ECGs, and exposure to BDC-1001 and pertuzumab.  All safety analyses will be conducted for the Safety Analysis Set. 
Pharmacokinetic Analysis: 
Individual and mean serum BDC-1001 exposure (eg, peak serum concentrations (Cmax) and trough serum concentrations 
[Cmin]) will be tabulated and plotted by arm and compared to those in the Phase 1 study using a population PK analysis 
approach.  Intersubject variability and drug accumulation will be evaluated.  
PK data from this study may also be used for separate pharmacokinetic/pharmacodynamic analyses; the results will be 
reported separately, if conducted.  
Exploratory pharmacodynamic analyses will include assessments of pharmacodynamic biomarkers in both tumor tissue 
and blood.  
The relationship between BDC-1001 concentration and selected efficacy and safety outcomes may be explored.  The 
correlation between biomarkers and clinical outcomes may be analyzed.   
Anti-Tumor Activity Analysis:  
The following anti-tumor activity endpoints will be analyzed and summarized for the subjects in FAS, with at least one 
evaluable post-baseline tumor assessment per RECIST v1.1: ORR, duration of response, disease control rate. 
Progression-free survival and overall survival will be analyzed and summarized for subjects in the Safety Population.  
Additional details will be provided in the statistical analysis plan.   
The ORR is defined as the proportion of subjects with best overall response of confirmed complete response (CR) or 
partial response (PR) as determined by the treating Investigator using RECIST v1.1. Confirmed CR or PR is defined as a 
repeat tumor assessment performed no less than 4 weeks after the criteria for response is first met. 
Biomarker Analysis:  
Exploratory biomarker analyses may include assessments of pharmacodynamic biomarkers in both tumor tissue and 
blood, when appropriate for data collected.  Biomarkers that may correlate with anti-tumor activity or 
immunomodulatory effects of BDC-1001 will be explored, as appropriate. 
BDC-1001 biological activity will be assessed by exploring pharmacodynamic or predictive biomarkers that may 
correlate with activity or help to identify subjects likely to respond to BDC-1001 and/or BDC-1001 plus pertuzumab 
combination treatment, when appropriate for data collected.  The correlation between biomarkers and clinical outcomes 
may be analyzed. 
Immunogenicity Analysis: 
Incidence, titer, and time-course of anti-BDC-1001 antibody (ADA) response will be reported by arm.  The potential 
correlation of immunogenicity with PK, pharmacodynamic, and safety parameters may be assessed. 
 
Number: CLIN-00059    Approved Date: 01 Aug 2024

Protocol BBI-20231001, Version 3.0, 01 August 2024 
BDC-1001 
 
 
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Page 17 of 93 
SCHEDULE OF ASSESSMENTS  
Table 1: 
Overview of Schedule of Assessments 
Event 
Screening a 
Cycle 1 
Cycle 2 and Beyond  EOT Visit b 
SFU b 
LTFU b 
Visit Day c 
 
Day 1 
D2 
D8 
Day 15 
D22 
Day 29 
D36 
Day 1 unless 
otherwise indicated 
14 d (±7d) 
after last Tx. 
28d (+7d) 
After last 
Tx 
q12 wks 
(±14d) After 
last Tx 
Visit Windows 
 
 
 
±1d 
±2d 
±2d 
±2d 
±2d 
±2d for Cycle 2 and 
Beyondd 
 
 
 
Timing 
 
BI 
EOI 
 
 
BI 
EOI 
 
BI 
EOI 
 
BI 
EOI 
 
 
 
Informed consent e 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
criteria f 
● 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administration of 
BDC-1001 q2w g 
 
● 
 
 
● 
 
● 
 
Days 1, 15, 29 
 
 
 
Administration of 
pertuzumab q3w h 
 
● 
 
 
 
 
● 
 
 
 
Days 1 and 22 
 
 
 
Medical history i 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics j 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height k 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination l 
● 
● 
 
● 
 
● 
 
● 
● 
 
 
BIm on  
Days 1, 15, 22, 29 
● 
● 
 
Weight, ECOG PS m 
● 
● 
 
 
 
● 
 
● 
● 
 
 
BIm on  
Days 1, 15, 22, 29 
● 
● 
 
Vital signs n 
● 
● 
BI (- 2 h) on Days 1, 15, 22, 29 and EOI (+ 5 min). Vital signs are not required EOI 
unless infusion reactions occur and after Cycle 2 unless clinically indicated. 
● 
● 
 
12-lead ECG o 
● 
● 
BI (- 2 h) on Days 1, 15, 22, 29 and EOI (+ 5 min). ECGs are not required EOI unless 
infusion reactions occur and after Cycle 2 unless clinically indicated. 
● 
 
 
ECHO or MUGA p 
● 
 
First assessment will be 6 weeks after the first study treatment then every 3 months 
during treatment, and start monitoring immediately in the presence of symptoms 
● 
 
 
SpO2 q 
● 
● 
 
● 
 
 
● 
 
● 
● 
 
BI on 
Days 1, 15, 22, 29 
● 
 
 
Number: CLIN-00059    Approved Date: 01 Aug 2024

Protocol BBI-20231001, Version 3.0, 01 August 2024 
BDC-1001 
 
 
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Page 18 of 93 
Event 
Screening a 
Cycle 1 
Cycle 2 and Beyond  EOT Visit b 
SFU b 
LTFU b 
Visit Day c 
 
Day 1 
D2 
D8 
Day 15 
D22 
Day 29 
D36 
Day 1 unless 
otherwise indicated 
14 d (±7d) 
after last Tx. 
28d (+7d) 
After last 
Tx 
q12 wks 
(±14d) After 
last Tx 
Visit Windows 
 
 
 
±1d 
±2d 
±2d 
±2d 
±2d 
±2d for Cycle 2 and 
Beyondd 
 
 
 
Timing 
 
BI 
EOI 
 
 
BI 
EOI 
 
BI 
EOI 
 
BI 
EOI 
 
 
 
Prior and concomitant 
medications  
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Days 1, 15, 22, 29 
● 
● 
 
AEs 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Days 1, 15, 22, 29 
● 
● 
 
HIV, HBV, HCV r 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test s 
● 
● 
Every 4 weeks (±3 days) after Cycle 1 Day 1 and at the EOT 
 
Chemistry and 
hematology t 
● 
● 
 
 
 
●t 
 
●t 
●  
 
 
BI on  
Days 1, 15, 29 
● 
● 
 
Thyroid Panel u 
● 
 
 
 
 
 
 
 
 
 
 
 
 
● 
 
 
Serum tumor markers v 
● 
● 
Coagulation w 
● 
 
 
 
 
 
 
 
 
 
 
 
 
● 
 
 
Urinalysis x 
● 
● 
 
 
 
 
 
 
 
 
 
If clinically indicated 
● 
 
 
PK y 
 
● 
● 
 
 
 
 
 
● 
● 
 
●y 
●y 
● 
 
 
ADA z 
 
● 
 
 
 
 
 
 
● 
 
 
●z 
 
● 
 
 
Serum biomarkers aa 
 
● 
●aa 
 
 
● 
●aa 
 
● 
●aa 
 
● 
●aa 
 
 
 
Plasma biomarkers bb 
 
● 
 
 
 
 
 
 
 
 
 
 
 
● 
 
 
Whole blood biomarkers 
(PBMC) cc 
 
● 
 
 
 
 
 
 
 
 
● 
C2 
Day 29 
 
● 
 
 
Whole blood (RNA) dd 
 
● 
● 
 
 
 
 
 
 
 
● 
 
 
 
 
 
Fresh tumor biopsy ee 
● 
 
 
 
 
 
 
 
 
 
● 
 
 
 
 
 
Archival tissue ff 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor assessmentgg 
● 
Every 6 weeks (± 7 days) during first 24 weeks after Day 1 of Cycle 1, and then every 12 weeks (± 7 days) 
Survival informationhh 
 
● 
Number: CLIN-00059    Approved Date: 01 Aug 2024

Protocol BBI-20231001, Version 3.0, 01 August 2024 
BDC-1001 
 
 
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Page 19 of 93 
Abbreviations: ADA = anti-BDC-1001 antibody; AE = adverse event; aPTT = activated partial thromboplastin time; BI = before infusion; CA=cancer antigen; C1 = Cycle 1; d or 
D = day; Disc = discontinuation; ECG = electrocardiogram; ECHO = echocardiogram; ECOG PS = Eastern Cooperative Oncology Group Performance Status; EOI = end of 
infusion, EOT = end of treatment; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; INR = international normalized ratio; LTFU = 
long-term follow-up; MUGA = multi-gated acquisition scan; PBMC = peripheral blood mononuclear cell; PK = pharmacokinetics; PT = prothrombin time; q2w = every 2 weeks; 
q3w = every 3 weeks; q12 wks = every 12 weeks; RNA = ribonucleic acid; SFU = Safety Follow-Up; SpO2 = peripheral capillary oxygen saturation; T4 = thyroxine; 
TSH = thyroid-stimulating hormone; Tx = treatment.  
a 
Assessments performed in the Screening Period must be done within 28 days prior to Cycle 1 Day 1, beginning with the day informed consent is obtained, with the following 
exceptions: concomitant medications, vital signs, physical exam, and ECOG PS assessment must be done within 14 days prior to Cycle 1 Day 1. 
b 
The subject should attend the EOT visit 14 days (± 7 days) after the last study treatment.   SFU, and LTFU are calculated from the date of the last administered study drug 
(BDC-1001 or pertuzumab).  
c 
All calculations of visit date should be based on Day 1, the first day a dose of study treatment is administered for each cycle. 
d 
Visit window is ± 2 days for study treatment administration. 
e 
Informed consent must be dated and signed before any study-specific procedure is performed (Section 6.2).  
f 
On Day 1 before the initial study drug treatment, recheck all Inclusion and Exclusion Criteria to meet protocol eligibility requirements. Refer to Section 4.1 and Section 4.2. 
g 
BDC-1001 will be administered q2w as described in Section 5.2.2 (i.e., on Days 1, 15, and 29 of each cycle).  Study treatment must be administered on Day 1. All subsequent 
doses may be administered within ± 2 days.  
h 
For subjects assigned to receive the combination of BDC-1001 and pertuzumab, pertuzumab will be administered q3w as described in Section 5.2.3; (i.e., on Days 1 and 22 of 
each cycle).  Study treatment must be administered on Day 1.The dose on  Day 22 may be administered ±2 d . 
i 
Medical history and tumor history should be completed as described in Section 6.6. 
j 
Demographic data will include age, gender, and self-reported race/ethnicity (Section 6.6). 
k 
Additional details regarding height are provided in Section 6.4. 
l 
A full physical examination is required at Screening.  All other physical examinations can be symptom directed. Additional information is provided in Section 6.4. 
m After completing 6 months of treatment, the Investigator and Sponsor may agree that the frequency of physical examinations and ECOG PS may be reduced to occur on an 
every-even-cycle basis unless more frequent assessments are clinically indicated. Additional details are provided in Section 6.7. 
n 
Vital signs assessments are described in Section 6.8.  Vital signs are not required after cycle 2 for EOI unless infusion reactions occur or unless clinically indicated.  The timing 
of collection pre- and post-infusion is presented in Table 8. 
o 
ECG is to be performed in accordance with Section 6.9. ECGs are not required after cycle 2 for EOI unless infusion reactions occur or unless clinically indicated.  The timing 
of collection pre-and post-infusion is presented in Table 8. 
p 
ECHO/MUGA is to be performed at Screening, 6 weeks after the first study treatment, then every 3 months during treatment and start monitoring immediately in the presence 
of symptoms.  Additional details are provided in Section 6.10.  
q 
Pulse oximetry will be performed as described in Section 6.11.  
r 
Additional information is provided in Section 6.14. 
s 
Pregnancy testing of female subjects of child-bearing potential will consist of a serum pregnancy test performed at Screening, and pregnancy testing on Cycle 1 Day 1 BI, 
every 4 weeks (±3 days) during treatment, and at EOT. Positive urine pregnancy test will be confirmed with a serum pregnancy test.  May be determined up to -48 hours before 
administration of study treatment.  Additional information is provided in Section 6.15. 
t 
Chemistry and hematology laboratory tests may be determined up to -48 hours before each dose and should be collected as described in Section 6.16.1 (chemistry) and 
Section 6.16.2 (hematology).  For subjects receiving BDC-1001 as a single agent, chemistry and hematology labs are only collected on Day 1, 15, and 29 of each Cycle.  For 
subjects receiving BDC-1001 in combination with pertuzumab, chemistry and hematology labs are collected on Days 1, 15, 22, and 29 for C1 and Days 1, 15, and 29 for all 
subsequent cycles. 
u 
TSH and free T4 will be performed as described in Section 6.17.  May be determined up to -48 hours before the dose. 
v 
Serum tumor markers (ie, CA 27.29 and CA 15-3, etc.), will be performed by local laboratory per standard of care (refer to Section 6.18). 
w Coagulation laboratory tests, PT (or INR) and/or aPTT as described in Section 6.16.3.  
x 
Urinalysis or urine dipstick as described in Section 6.16.4.  May be determined up to -48 hours before each dose.  
Number: CLIN-00059    Approved Date: 01 Aug 2024

Protocol BBI-20231001, Version 3.0, 01 August 2024 
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y 
Serum PK will be collected before BDC-1001 infusion and up to 15 minutes after the end of BDC-1001 infusion, on Days 1 and 29 of Cycles 1, 2, 3, and 4; Day 1 of every 
other odd cycle after every 12 week tumor assessment (ie, Cycle 5, 7, 9, etc); Day 29 of every other even cycle (ie, Cycle 6, 8, 10, etc) before every 12 week tumor assessment; 
and at EOT (Section 6.19). 
z 
Serum ADA will be collected before BDC-1001 infusion on Days 1 and 29 of Cycles 1, 2, 3, and 4;  before BDC-1001 infusion on Day 1 of every other odd cycle after every 
12 week tumor assessment (ie, Cycle 5, 7, 9, etc); before BDC-1001 infusion on Day 29 of every other even cycle (ie, Cycle 6, 8, 10, etc) before every 12 week tumor 
assessment; and at EOT (Section 6.20).   
aa 
Serum biomarkers will be collected on Cycle 1 Day 1 (before BDC-1001 infusion and 4 hrs±1 hr post-EOI), Cycle 1 Day 15 (before BDC-1001 infusion and 4 hrs±1 hr 
 
post-EOI), Cycle 1 Day 29 (before BDC-1001 infusion and 4 hrs ±1 hr post-EOI), Cycle 4 Day 1 (before BDC-1001 infusion and 4 hrs±1 hr post-EOI), and Cycle 5 (before 
 
BDC-1001 infusion and 4 hrs±1 hr post-EOI), (Section 6.21).  
bb Plasma biomarkers will be collected before BDC-1001 infusion on Cycle 1 Day 1 and EOT (Section 6.21). 
cc Whole blood biomarkers for PBMC will be collected before BDC-1001 infusion on Cycle 1 Day 1, Cycle 1 Day 36 (during on treatment biopsy, if conducted),  before BDC-
1001 infusion on Cycle 2 Day 29, and EOT (Section 6.21). 
dd Whole blood for RNA will be collected before BDC-1001 infusion on Cycle 1 Day 1 and 4 hrs±1 hr post-EOI, and Cycle 1 Day 36 (during on treatment biopsy, if conducted) 
(Section 6.21). 
ee Screening fresh tumor tissue biopsy is required for all subjects (Section 6.22.1).  On-treatment biopsy at Cycle 1 Day 36 may be collected if safely accessible and clinically 
feasible, at the discretion of the Investigator.  An optional additional biopsy may be collected preferably at time of progression, response, or at any time during the study.  
ff Archival tumor tissue must be submitted if a fresh biopsy is not collected (Section 6.22.2). 
gg Tumor assessments should be done during the Screening Period within 28 days before Cycle 1 Day 1, every 6 weeks (± 7 days) during first 24 weeks after Day 1 of Cycle 1, 
and then every 12 weeks (± 7 days).  Brain scans are required only for subjects with known brain metastases.  Tumor measurement will be conducted while the subject remains 
on study until progression of disease, withdrawal of consent, death, or loss to follow up.  Subjects who experience an objective response (ie, tumor reduction) should have a 
confirmatory assessment performed 4 weeks (+7 days) after initial response. Additional details are provided in Section 6.23. 
hh Survival information should be collected as described in Section 6.24. 
Number: CLIN-00059    Approved Date: 01 Aug 2024

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Table 2: 
Overview of Schedule of Assessments – Maintenance Phase - Q2W Dosing 
Event  
Treatment Cycle Days 
Consent to Maintenance Phase 
Prior to performing any assessments or procedures in the 
Maintenance Phase 
Administration BDC-1001  
Days 1, 15, and 29 
Physical examination  
Per local SOC/investigator discretion 
Weight, ECOG PS  
Per local SOC/investigator discretion 
Vital signs  
Per local SOC/investigator discretion 
12-lead ECG  
Per local SOC/investigator discretion 
AEs/SAEs 
Per local SOC/investigator discretion 
(Only SAEs and other reportable events such as pregnancy will be 
collected and reported to Sponsor for subjects during the 
Maintenance Phase.) 
ECHO or MUGA  
Per local SOC/investigator discretion 
SpO2  
Per local SOC/investigator discretion 
Serum Pregnancy (if applicable) 
Monthly 
Chemistry  
Per local SOC/investigator discretion 
Hematology  
Per local SOC/investigator discretion 
Thyroid Panel/TSH  
Per local SOC/investigator discretion 
Coagulation  
Per local SOC/investigator discretion 
Urinalysis  
Per local SOC/investigator discretion 
Tumor Assessment  
Per local SOC/investigator discretion 
Post Treatment Safety Evaluation  
Per local SOC/investigator discretion 
Abbreviations: AE = adverse event; ECG = electrocardiogram; ECHO = echocardiogram; ECOG PS = Eastern 
Cooperative Oncology Group Performance Status; MUGA = Multigated Acquisition Scan; SAE = serious adverse 
event; SOC = standard of care; SpO2 = peripheral capillary oxygen saturation; TSH = thyroid -stimulating hormone  
 
For the Maintenance Phase, no data will be entered into electronic case report forms. Lab results 
will not be submitted to the Sponsor and radiographic images will not be submitted to the study 
central imaging vendor. Subjects should undergo a post treatment safety evaluation per local 
standard of care and as clinically directed in the opinion of the Investigator. 
 
Number: CLIN-00059    Approved Date: 01 Aug 2024

Protocol BBI-20231001, Version 3.0, 01 August 2024 
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation  
Definition 
1L, 2L, 3L 
first-line, second-line, third-line 
ASCO 
American Society of Clinical Oncology 
ADA 
anti-BDC-1001 antibody  
ADCC 
antibody-dependent cell-mediated cytotoxicity 
AE 
adverse event 
ALT 
alanine aminotransferase 
APC 
antigen presenting cells 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
ATC 
anatomical therapeutic classification 
AUC 
area under the concentration-time curve 
BI 
before infusion 
BUN 
blood urea nitrogen 
CA27.29 or CA15-3 
cancer antigen 27.29 or 15-3 
CAP 
College of American Pathologists 
C1D1 
Cycle 1 Day 1 
CI 
confidence interval 
CLIA 
Clinical Laboratory Improvement Amendments 
Cmax 
peak serum concentration  
Cmin 
trough serum concentration 
CQA 
Clinical Quality Assurance 
CR 
complete response 
CRS 
cytokine release syndrome 
CT 
computed tomography 
DCR 
disease control rate 
DOR 
duration of response  
ECG 
electrocardiogram 
ECHO 
echocardiogram 
ECOG 
Eastern Cooperative Oncology Group  
eCRF 
electronic case report form  
EOI 
end of infusion 
EOT 
end of treatment 
ERBB2 
erb-b2 receptor tyrosine kinase 2 
FAS 
Full Analysis Set  
FIH 
first-in-human 
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Abbreviation  
Definition 
GCP 
Good Clinical Practice  
HBcAb 
hepatitis B core antibody 
HBsAg 
hepatitis B surface antigen  
HBV 
hepatitis B virus  
HCV 
hepatitis C virus  
HER2 
human epidermal growth factor receptor 2 
HER2+ 
human epidermal growth factor receptor 2-positive 
HIPAA 
Health Insurance Portability and Accountability Act  
HIV 
human immunodeficiency virus  
HR 
hazard ratio 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use  
iCPD 
immune confirmed progressive disease 
IEC 
Independent Ethics Committee 
IFNγ 
interferon gamma 
IL 
interleukin 
INR 
international normalized ratio 
IP 
inducible protein 
IRB 
Institutional Review Board  
iRECIST 
Immunotherapy Response Evaluation Criteria in Solid Tumors 
IRR 
infusion-related reaction 
ISAC 
immune stimulating antibody conjugate 
iUPD 
immune unconfirmed progressive disease 
IV 
intravenous 
LTFU 
long-term follow-up 
LVEF 
left ventricular ejection fraction 
mAb 
monoclonal antibody 
MBC 
metastatic breast cancer 
MCP 
monocyte chemoattractant protein 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIP 
macrophage inflammatory protein 
MRI 
magnetic resonance imaging  
MTD 
maximum tolerated dose  
MUGA 
multi-gated acquisition scan 
NCI CTCAE v5.0 
National Cancer Institute Common Terminology Criteria for Adverse Events 
version 5.0 
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Abbreviation  
Definition 
ORR 
objective response rate  
OS 
overall survival 
PCR 
polymerase chain reaction 
PD 
progressive disease 
PDAS 
Pharmacodynamic Analysis Set 
PFS 
progression-free survival  
PK 
pharmacokinetic  
PKAS 
Pharmacokinetic Analysis Set 
PR 
partial response 
PS 
performance status 
PT 
prothrombin time 
q1w, q2w, q3w 
Weekly, every 2 weeks, every 3 weeks 
QTcF 
QT corrected - Fridericia's correction formula 
RECIST v1.1 
Response Evaluation Criteria in Solid Tumors version 1.1 
RNA 
ribonucleic acid 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan  
SAR 
serious adverse reaction 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SD 
stable disease 
SFU 
Safety Follow-Up 
SI 
International System of Units 
SJS 
Stevens-Johnson syndrome 
SOC 
standard of care 
SOP 
standard operating procedure 
SRC 
Safety Review Committee 
SVT 
supraventricular tachycardia 
T3 
triiodothyronine 
T4 
thyroxine  
TEAE 
treatment-emergent adverse event 
TEN 
toxic epidermal necrolysis 
TLR 
toll-like receptor 
TNFα 
tumor necrosis factor alpha 
TSH 
thyroid-stimulating hormone  
ULN 
upper limit of normal  
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Abbreviation  
Definition 
WHO 
World Health Organization  
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DEFINITION OF TERMS 
Term  
Definition 
Applicable regulatory 
requirements 
Any law(s) and regulation(s) addressing the conduct of clinical trials of 
investigational products. 
Baseline 
The last assessment before first study treatment administration. 
End of Study 
When the last subject has completed their Safety Follow-Up (SFU). 
End of Treatment (EOT) 
The date of the last study drug administration. 
Enrolled 
A subject is considered enrolled once the Principal Investigator or 
designee completes assessment of subject eligibility and confirms that the 
subject meets all inclusion and no exclusion criteria for the trial. 
Follow-up Phase  
Starts 1 day after discontinuation of study treatment and ends on the 
subject's last follow-up visit.  
Maximum Tolerated Dose 
(MTD) 
The highest dose that will produce the desired effect without resulting in 
unacceptable side effects.   
Screening Period 
Begins on the day the first Screening assessment is performed according 
to the Schedule of Assessments and ends on the day before subject's first 
study treatment administration.  The Screening Period is a maximum of 
28 days. 
Study treatment  
Study treatment refers to medicinal products under investigation in this 
study, and whose use is required by this study.  This includes BDC-1001 
and pertuzumab. 
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1. 
INTRODUCTION 
1.1. 
Disease Background 
Breast cancer is the second most common cancer in women after skin cancer.  In 2020, 
2.3 million women were diagnosed with breast cancer and 685,000 deaths attributed to breast 
cancer were reported worldwide (World Health Organization 2021).  About 20% of breast 
cancers have high expression of human epidermal growth factor receptor 2 (HER2), also known 
as erb-b2 receptor tyrosine kinase 2 (ERBB2).  HER2 is a proto-oncogene that encodes a 
transmembrane protein involved in signal transduction pathways that promote cell growth and 
differentiation.   
Treatments approved for human epidermal growth factor receptor 2-positive (HER2+) breast 
cancer include monoclonal antibodies, trastuzumab, pertuzumab, and margetuximab; small 
molecule tyrosine kinase inhibitors, lapatinib, neratinib, tucatinib, pyrotinib, and antibody-drug 
conjugates, ado-trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd).  These 
therapies are moderately to highly effective and are most recently associated with objective 
response rates (ORR) of 25-82.7% and Investigator-assessed median progression-free survival 
(PFS) of 10-25.1 months in second-line (2L) HER2+ metastatic breast cancer (MBC; 
ENHERTU®), and an objective response rate (ORR) of 82.7% and Investigator-assessed median 
PFS of 25.1 months (ENHERTU® USPI 2022, DESTINY-Breast03 trial) in third-line (3L) 
HER2+ MBC (Hurvitz et al 2023). However, patients with MBC eventually develop tumor 
relapse, and currently the 5-year survival rate for women with MBC is only about 29%, while the 
5-year survival rate for men with MBC is 19%.  Clinical resistance, the development of local 
recurrence or metastasis, and significant morbidity remain prominent issues associated with the 
management of HER2+ breast cancer.  Clinically significant toxicities of HER2-directed 
therapies include gastrointestinal and hematological toxicities, infection, interstitial lung disease, 
and left ventricular dysfunction.  Thus, an unmet need persists for novel therapies for HER2+ 
MBC following the use of trastuzumab deruxtecan, and for therapies that may improve the safety 
and efficacy of HER2-directed interventions in earlier lines of therapy.  
1.2. 
Study Treatment Background 
1.2.1. 
BDC-1001 Background  
BDC-1001 is an immune-stimulating antibody conjugate (ISAC) designed to be delivered 
systemically and act locally by targeting HER2-expressing tumors and related metastatic disease 
for destruction by the innate and adaptive immune systems.  BDC-1001 consists of an 
investigational biosimilar of the humanized monoclonal antibody (mAb) trastuzumab (EG12014) 
that is chemically conjugated to a toll-like receptor (TLR)7/8 agonist (payload) with an 
intervening non-cleavable linker (Figure 1).  Additional information is provided in the current 
BDC-1001 Investigator’s Brochure. 
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Figure 1: 
Schematic Representation of BDC-1001 
 
The immunosuppressive tumor microenvironment often prohibits dendritic cells and other 
antigen presenting cells (APCs) from effectively stimulating tumor reactive T cells.  The 
presence of TLR7/8 agonist molecules allows BDC-1001 to combine the anti-tumor effects of 
trastuzumab with localized stimulation of the immune system (Carmi et al. 2015; Singh et al. 
2014; Sagiv-Barfi et al. 2018).  The proposed mechanism of action depicted in Figure 2 is 
tripartite with BDC-1001 binding to HER2 expressing tumor cells via the antibody variable 
region leading to tumor cell killing and phagocytosis.  The immune-stimulating TLR7/8 agonist 
attached to BDC-1001 activates myeloid APCs such as macrophages and dendritic cells and is 
expected to lead to increased cytotoxicity, processing and presentation of tumor neoantigens that 
subsequently stimulate T cell-mediated immunity (Engblom, Pfirschke, and Pittet 2016; Schon 
and Schon 2008; Marabelle et al. 2017).  Importantly, BDC-1001 was designed to mitigate the 
risk of non-specific immune activation associated with TLR7/8 activation as the linker-payload 
is not active until it is internalized by immune cells that express the requisite Fc gamma receptors 
and TLR7/8. 
In pre-clinical models, treatment with BDC-1001 surrogates led to complete and durable 
regression in multiple human tumor cell lines (including human breast cancer cell lines) with 
variable levels of HER2 expression that were refractory to treatment with the naked anti-HER2 
antibody, trastuzumab.  Mechanistic studies indicate T cells and phagocytes are required for 
anti-tumor activity. 
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Figure 2: 
Proposed Mechanism of Action for BDC-1001 
 
The proposed mechanism of action is tripartite, involving the antibody variable domain, the antibody Fc region and the TLR7/8 
binding domain.  (A) Fv portion of antibody recognizes HER2 expressing cancer cells; (B) APCs recognize antibody bound to 
HER2 expressing cancer cells via their Fc gamma receptors (FcγRs) and internalize tumor-immune complex following FcR 
clustering; (C) Once internalized, the TLR7/8 agonist attached to BDC-1001 gains access to the phagolysosome and mediates 
downstream events associated with TLR activation.  Note that the number of HER2 molecules and bound BDC-1001 have been 
reduced to 1 each for schematic purpose. 
1.2.1.1. 
Nonclinical Studies 
The pharmacology, safety pharmacology, pharmacokinetics (PK), and toxicology of BDC-1001 
have been examined in nonclinical studies.  Details of these experiments are described in the 
current BDC-1001 Investigator’s Brochure.  An overview of relevant study data is provided 
below. 
Preclinical studies demonstrate that BDC-1001 murine surrogates (BB087) can elicit better anti-
tumor activity compared with trastuzumab (see BDC-1001 Investigator’s Brochure), and the 
anti-tumor activity can be enhanced when administered in combination with pertuzumab in 
HER2-expressing breast tumor models (JIMT-1 cell line derived from trastuzumab-resistant 
breast cancer) where BDC-1001 monotherapy did not elicit complete regression.  The 
combination of BDC-1001 surrogate and pertuzumab also elicits superior anti-tumor activity as 
compared to the combination of trastuzumab and pertuzumab (Figure 3).  
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Figure 3: 
BDC-1001.S + Pertuzumab Augment Anti-Tumor Efficacy in JIMT-1 Model 
 
SCID/beige mice with JIMT-1 HER2 IHC2+ tumors (n=6 per group) were treated systemically with the indicated 
test article(s) Q5Dx4 (dashed lines).  The BDC-1001 surrogate (BB087) was administered at the indicated dose. 
% TGI is calculated on Day 20 relative to trastuzumab and pertuzumab combination: ((AverageControl-
AverageTreated)/AverageControl)*100.  
1.2.1.2. 
Clinical Studies 
As of March 2024, Bolt Biotherapeutics is conducting 2 clinical studies of BDC-1001.  
Study BBI-20201001, is a first-in-human (FIH) Phase 1/2 clinical study investigating BDC-1001 
as monotherapy and in combination with nivolumab in advanced or metastatic HER2-positive 
colorectal, gastroesophageal, endometrial, and breast cancer. Study BBI-20231001 is a Phase 2 
study investigating BDC-1001 as monotherapy and in combination with pertuzumab in patients 
with metastatic HER2-positive breast cancer. No final efficacy or safety data are available and 
interim safety results from both studies are summarized below.   
As of the data cutoff date of 23 January 2024, 167 patients received at least 1 dose of BDC-1001 
either in monotherapy or in combination with nivolumab (BBI-20201001 n=164 and 
BBI-20231001 n = 3). The most common treatment-emergent adverse events (TEAEs) occurring 
in greater than 10% of patients were infusion related reaction (27.5%), fatigue (25.1%), nausea 
(25.1%), abdominal pain (20.3%), anemia (17.4%), vomiting (16.8%), diarrhea (15.0%), 
constipation (13.8%), decreased appetite (12.6%), dyspnea (12.0%), and pyrexia (10.2%). Most 
of these events were mild or moderate in severity. 
Infusion-related reactions (IRRs) are the most frequently occurring TEAE in subjects treated 
with BDC-1001. All reported events were mild to moderate (grade 1 or grade 2 per CTCAE), 
and all but 1 were assessed as not serious. The single serious grade 2 IRR event was considered 
resolved with treatment with diphenhydramine, and the BDC-1001 dose was not changed.  
In the 2 ongoing clinical studies with BDC-1001, 53 subjects (32.3%) experienced at least 
1 serious adverse event (SAE) in the BDC-1001 treated population.  The most common SAEs 
0
10
20
30
40
0
500
1000
1500
JIMT-1 (HER2 IHC2+)
Days Post Initial Treatment
Tumor Volume (mm3)
BDC-1001.S (5mpk)
BDC-1001.S (1mpk) + Pert (5mpk)
BDC-1001.S (2mpk) + Pert (5mpk)
BDC-1001.S (5mpk) + Pert (5mpk)
Tras (5mpk) + Pert (5mpk)
Isotype 10mpk
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occurring in ≥ 2 patients in the BDC-1001 treated population included abdominal pain (3.6%), 
acute kidney injury, anemia, dyspnea, and urinary tract infection (each 1.8% respectively), and 
disease progression, gastric hemorrhage, large intestinal obstruction, pneumonia, small intestinal 
obstruction, and urinary tract obstruction (each 1.2% respectively).  Of the reported SAEs, 9 
SAEs were considered related to BDC-1001. Seven SAEs were grade 2 or 3 in severity with 1 
event of pulmonary hemorrhage assessed as grade 4 and 1 event of death assessed as grade 5.  
Cumulatively, 67 deaths occurred in the BDC-1001 program. Of these deaths, 52 were attributed 
to progressive disease, 2 to adverse events (AEs), 1 to a car accident, and 12 were assessed as 
“unknown” or the cause of death was “blank”. All unknown or blank causes of death were 
attributed to progressive disease.  
Of the 2 deaths attributed to AEs, 1 was reported as a head injury with no relationship to 
BDC-1001, and 1 was reported as death. The death event was unwitnessed at home as noted by 
the investigator which was likely caused by underlying disease. As the investigator could not 
definitively rule out a potential contribution by BDC-1001, the case is conservatively being 
assessed as related to BDC-1001 pending further clarifying information.  
Eight subjects experienced 9 AEs leading to discontinuation of BDC-1001: 4 events were related 
SAEs, grade 3 ejection fraction decreased and supraventricular tachycardia, grade 4 pulmonary 
hemorrhage, and grade 5 death.  
Based on the cumulative data to date, no important identified risks were assessed as of the data 
cutoff date.  However, 1 important potential risk of decreased left ventricular ejection fraction 
was identified based on class effect, mechanism of action, AE reports, and ejection fraction 
readings. Treatment management of decreased left ventricular ejection fraction should be 
managed as per protocol.  
For more details, refer to the current BDC-1001 Investigator’s Brochure. 
1.2.2. 
Pertuzumab Background  
Pertuzumab is a mAb that targets HER2 and prevents dimerization of HER2 with other members 
of the HER family (HER1, HER3, and HER4), thereby blocking ligand-activated downstream 
signaling.  Pertuzumab is also capable of mediating antibody-dependent cell-mediated 
cytotoxicity (ADCC) in cell-based assays.  Pertuzumab and trastuzumab bind to distinct epitopes 
on the HER2 receptor without competing.  These molecules have complementary mechanisms 
for disrupting HER2 signaling.  This results in augmented anti-proliferative activity in vitro and 
in vivo when pertuzumab and trastuzumab are given in combination.  
Pertuzumab is approved in combination with trastuzumab and chemotherapy for the treatment of 
subjects with early stage and metastatic HER2+ breast cancers (PERJETA® USPI 2021).  While 
it is not approved for use in the absence of trastuzumab, or in later lines of therapy, the addition 
of pertuzumab to trastuzumab, and docetaxel in the pivotal, placebo-controlled, first-line (1L) 
MBC study, CLEOPATRA resulted in a 6.1 month improvement in PFS (12.4 months vs 
18.5 months; hazard ratio [HR]=0.62, p<0.0001; 95% confidence interval [CI]=0.51, 0.75).  At 
the time of the final overall survival (OS) analysis, the pertuzumab-containing arm demonstrated 
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a statistically significant OS advantage over the placebo arm (HR=0.68, p=0.0002; 95% CI=0.56, 
0.84), as well, with an increase in median OS to 56.5 months in the pertuzumab-treated group 
from 40.8 months in the placebo-treated group.  Similar benefit has been seen with the addition 
of pertuzumab to trastuzumab plus chemotherapy in the neoadjuvant (NEOSPERE) pathological 
complete response (CR=39.3% vs. 21.5%; p=0.0063), and adjuvant (APHINITY HR=0.82; 
95% CI=0.68, 0.99 with no statistical difference in OS) settings.   
Safety signals (> 5% increase) associated with the addition of pertuzumab to trastuzumab plus 
chemotherapy in the metastatic setting (PERJETA® USPI 2021, CLEOPATRA trial) include 
increases in the following: mucosal inflammation (28 vs. 20%), rash (34 vs. 24%), diarrhea 
(67 vs. 46%), febrile neutropenia (14 vs. 8%).  Safety signals in the neoadjuvant settings 
(NEOSPHERE) were similar, with mucosal inflammation (26 vs. 21%), pyrexia (17 vs. 10%), 
rash (26 vs. 21%), diarrhea (46 vs. 34%), stomatitis (18 vs. 7%), and dysgeusia (15 vs. 10%) 
being increased in the pertuzumab/trastuzumab/chemotherapy arms relative to the 
trastuzumab/chemotherapy/placebo arm.  It is noteworthy that, when pertuzumab was added to 
trastuzumab without chemotherapy in the neoadjuvant setting, rates of these toxicities were not 
increased in the pertuzumab plus trastuzumab group relative to the trastuzumab plus 
chemotherapy group: mucosal inflammation (3 vs. 21%), pyrexia (8 vs. 10%), (11 vs. 21%), 
diarrhea (28 vs. 34%), stomatitis (7 vs. 5%), and dysgeusia (10 vs. 5%).  This suggests that these 
toxicities, primarily associated with the chemotherapeutic agents, may be exacerbated by the 
addition of trastuzumab or trastuzumab plus pertuzumab, but that they are not related to 
trastuzumab, pertuzumab, or the combination of trastuzumab and pertuzumab in the absence of 
chemotherapy. 
Left ventricular dysfunction, a known risk associated with HER2 inhibition, was not increased in 
pertuzumab-treated subjects in the pivotal pertuzumab trial in 1L MBC; however, in neoadjuvant 
trials, the rate of left ventricular dysfunction > 10% and to < 50% was increased as high as 8% 
among subjects receiving pertuzumab/trastuzumab/chemotherapy regimen relative to 1-3% in 
trastuzumab/chemotherapy-treated subjects (PERJETA® USPI 2021).  In the adjuvant 
APHINITY trial (PERJETA® USPI 2021), LVEF declines of > 10% and to < 50% were seen in 
an equal percentage of subjects treated with pertuzumab/trastuzumab/chemotherapy and those 
receiving trastuzumab/chemotherapy without pertuzumab (3%).  Taken in totality, these data 
suggest that pertuzumab may mildly increase the cardiac dysfunction associated with 
trastuzumab. 
All of these risks associated with the addition of pertuzumab to trastuzumab plus chemotherapy 
have been assessed to be acceptable for a highly effective treatment regimen. 
Since BDC-1001 consists of a biosimilar of trastuzumab, BDC-1001, the combination of BDC-
1001 with pertuzumab has the potential for a favorable safety and efficacy profile in subjects 
with advanced HER2+ breast cancer.  Further details on the safety and efficacy of pertuzumab 
are provided in the current pertuzumab Investigator’s Brochure. 
1.3. 
Study Rationale 
Current therapies are moderately to highly effective against HER2+ breast cancer, with 
combination therapy of trastuzumab, pertuzumab, and a taxane providing median PFS of 
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18.7 months, and median OS of 56.5 months in 1L treatment of MBC (PERJETA® USPI 2021, 
CLEOPATRA trial).  More recently, fam trastuzumab-deruxtecan-nxki (ENHERTU®) provided 
an Investigator-assessed median PFS of 25.1 months (ENHERTU® USPI 2022 in subjects with 
2L treatment for MBC, DESTINY-Breast03 trial), and a median PFS of 18.8 and 19.4 months, 
with a median OS of 29.1 and 39.2 months in subjects with 3L MBC (DESTINY-Breast01 and 
02 trials, respectively) (Hurvitz et al, 2023; Modi et al, 2020; Andrế et al, 2023).  While 
trastuzumab deruxtecan (ENHERTU) has changed the breast cancer treatment landscape, no 
effective treatments are available for subjects with HER2+ MBC whose tumors are refractory to 
or relapsed after receiving trastuzumab deruxtecan.  
In addition, cytopenias, cardiac dysfunction, gastrointestinal toxicity, and pneumonitis are 
significant toxicities associated with current MBC therapies.  Thus, there is an unmet medical 
need for safe effective therapies for subjects with HER2+ MBC, who are refractory to or have 
relapsed following trastuzumab deruxtecan treatment. 
BDC-1001 is a novel ISAC, covalently linking a TLR7/8 agonist to a trastuzumab biosimilar.  In 
cellular proliferation assays, performed in the absence of immune cells, BDC-1001 and 
trastuzumab elicit similar levels of in vitro ADCC, antibody-dependent cellular phagocytosis, 
and inhibition of cancer cell proliferation in HER2-expressing cell lines.  In vitro modeling in the 
presence of freshly harvested antibody presenting cells (APCs) demonstrate that this novel ISAC 
activates primary human myeloid APCs in an FcR and TLR-dependent manor.  In vivo, 
BDC-1001 murine surrogates (BB087) can elicit better anti-tumor activity compared with 
trastuzumab (see BDC-1001 Investigator’s Brochure).  Comparison of local delivery of 
trastuzumab combined with the TLR agonist to systemic delivery of the surrogate ISAC 
(T785-ISAC) in a murine model demonstrated that only the ISAC was successful in reducing 
tumor burden (Ackerman et al. 2021).  The anti-tumor activity of the ISAC can be further 
enhanced when administered in combination with pertuzumab in HER2-expressing, trastuzumab-
resistant breast tumor models (JIMT-1, CALU-3, NCI-N87).  The combination of the BDC-1001 
surrogate and pertuzumab also elicits superior anti-tumor activity as compared to the 
combination of trastuzumab and pertuzumab (Figure 3) (see BDC-1001 Investigator’s Brochure).  
The study population consists of subjects with HER2+ MBC who have received 2 or more prior 
therapies targeting HER2, with trastuzumab deruxtecan (ENHERTU®) as 1 of the prior therapies.  
These subjects represent an unmet medical need with high benefit:risk potential for clinical trial 
exploration.   
BDC-1001 is also being evaluated in the ongoing dose escalation and expansion study 
(BBI-20201001) in subjects with advanced HER2-expressing solid tumors (see Section 1.2.1.2).  
The clinical experience has demonstrated acceptable safety and promising early clinical activity 
in a heavily pre-treated subject population.  As of 11 August 2023, 131 subjects received 
BDC-1001 (94 as monotherapy [Part 1] and 37 in combination with nivolumab [Part 2]).  
Six patients had a response (1 complete response and 5 partial responses).  Fourteen patients had 
stable disease lasting at least 24 weeks.  The median (minimum, maximum) durations of 
treatment for this efficacy data cut were 3.79 weeks (0.1, 83.4) in the BDC-1001 monotherapy 
and 5.29 weeks (0.1, 46.4) for subjects receiving BDC-1001 in combination with nivolumab 
(Li, et al, 2023a). 
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Because BDC-1001 consists of a biosimilar of trastuzumab, and the addition of pertuzumab has 
been demonstrated to significantly enhance the pre-clinical and clinical activity of trastuzumab, 
as well as the pre-clinical activity of BDC-1001, and because the safety profile of the 
trastuzumab + pertuzumab combination, in the absence of chemotherapy and of BDC-1001 are 
favorable, BDC-1001 as a single agent and in combination with pertuzumab has the potential for 
tolerable safety as well as significant efficacy in subjects with advanced HER2+ breast cancer.  
BDC-1001 may provide particular benefit to subjects whose tumors demonstrate resistance to or 
have experienced relapse following trastuzumab deruxtecan, and who have no other treatment 
options.   
Rationales for the study design and dose are provided in Section 3.2.   
1.4. 
Risk/Benefit Assessment 
In this study, BDC-1001, a novel ISAC that retains the functionality of trastuzumab while adding 
the immune-activating functionality of APCs via TLR7/8 engagement, is studied alone and in 
combination with pertuzumab in subjects with relapsed/refractory advanced HER2+ breast 
cancer, following trastuzumab deruxtecan therapy.  There are currently no approved treatment 
options for this subject population.  Both pre-clinical and clinical data support the favorable 
benefit:risk assessment for this combination.   
In vitro, BDC-1001 and trastuzumab elicit similar levels of in vitro ADCC, antibody-dependent 
cellular phagocytosis, and inhibition of cancer cell proliferation in HER2-expressing cell lines.  
However, in vivo, BDC-1001 murine surrogates elicit better anti-tumor activity compared with 
trastuzumab (see BDC-1001 Investigator’s Brochure).  Preclinical data not only demonstrate 
enhanced activity when pertuzumab is added to trastuzumab, the addition of pertuzumab to the 
BDC-1001 surrogate in murine models also significantly increased tumor growth inhibition 
relative to that of the trastuzumab plus pertuzumab combination. 
Clinically, pertuzumab in combination with trastuzumab and chemotherapy enhances the 
efficacy of trastuzumab in 1L metastatic HER2+ MBC (PFS HR=0.62, p0.0001; OS HR=0.68, 
95% CI, p=0.0002), as well as early breast cancer (HR= 0.82 [0.68, 0.99], and has been approved 
in both settings.  It is noteworthy that the addition of pertuzumab to trastuzumab plus docetaxel 
adds little to the rate of overall AEs of the combination.  Mild increases were seen in the rates of 
mucosal inflammation (28 vs. 20%), rash (34 vs. 24%), diarrhea (67 vs. 46%), and febrile 
neutropenia (14 vs. 8%).  In the neoadjuvant setting, these same toxicities, which are associated 
with the trastuzumab, pertuzumab, plus docetaxel combination, were not increased when 
trastuzumab and pertuzumab were given in combination, in the absence of chemotherapy.  Left 
ventricular dysfunction, a known risk associated with HER2 inhibition, has been shown to be 
somewhat increased (7-8% vs. 2-3% decrease in LVEF of > 10%, to < 50%) by the addition of 
pertuzumab to trastuzumab-based regimens in some but not all early stage breast cancer studies 
(see Section 1.2.2; PERJETA® USPI 2021).  These toxicities have all been deemed by clinicians, 
and regulatory bodies as well within acceptable range for highly effective treatment. 
BDC-1001 as a single agent has also shown promising efficacy among subjects with 
relapsed/refractory HER2+ malignancies.  At the dose for this trial (20 mg/kg q2w dose), 
BDC-1001 monotherapy had an ORR of 67% (4/6) in subjects with documented 
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HER2+ advanced solid tumors.  At the time of the data cutoff, no subjects with breast cancer 
were enrolled in the 20 mg/kg q2w cohort; however, 1 subject with HER2+ breast cancer, who 
was enrolled after the data cutoff date, is currently receiving BDC-1001 at the recommended 
phase 2 dose (RP2D) and has SD (12% tumor shrinkage) at Week 6 (date of tumor assessment: 
13 March 2023), indicating anti-tumor activity in HER2+ breast cancer.   
To date, the ongoing trials for BDC-1001, BBI-20201001 and BBI-20231001, demonstrate 
acceptable safety and promising clinical activity for this novel ISAC.  BDC-1001 has been well 
tolerated and interim safety data are presented in Section 1.2.1.2.  No IRRs were identified.  
While left ventricular ejection fraction decreased has been assessed as an important potential risk 
for BDC-1001, as of the data cutoff date of January 2024, no occurrences have been observed in 
Study BBI-20231001. Treatment of this event should be managed per the protocol.  Overall, 
based on the totality of safety information collected to 23 January 2024, it is the opinion of the 
sponsor that the benefit-risk assessment of BDC-1001 in the populations under study remains 
acceptable and warrants continued investigation in clinical trials. 
The 20 mg/kg q2w dose, chosen for this study, is 50% of a dose that was well tolerated, and on 
which no dose-limiting toxicities were observed in the FIH study.  For this reason, a 3 subject 
run-in is not felt to be required in this study.  All enrolled subjects will be monitored closely for 
safety.   
Given the mechanism of action of BDC-1001, its trastuzumab backbone, the enhanced pre-
clinical and clinical activity conferred by pertuzumab when added to trastuzumab, pre-clinical 
evidence of enhanced clinical activity when pertuzumab is added to BDC-1001, and data 
available on the safety and efficacy of BDC-1001, the benefit/risk ratio remains positive for 
continued evaluation of BDC-1001 as a single agent and for evaluation of BDC-1001 in 
combination with pertuzumab in subjects with HER2+ MBC whose tumors are refractory to or 
have relapsed after trastuzumab deruxtecan. 
For more details, refer to the current BDC-1001 Investigator’s Brochure. 
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2. 
STUDY OBJECTIVES 
2.1. 
Objectives and Endpoints 
The objectives and endpoints to be evaluated in the study are outlined in Table 3. 
Table 3: 
Objectives and Endpoints 
Primary Objectives 
Primary Endpoints 
• Efficacy: To evaluate the preliminary anti-tumor 
activity of BDC-1001 as a single agent and in 
combination with pertuzumab in subjects with 
previously treated HER2+ MBC 
• ORR according to RECIST v1.1  
Secondary Objectives 
Secondary Endpoints 
• Efficacy: To evaluate the preliminary anti-tumor 
activity of BDC-1001 as a single agent and in 
combination with pertuzumab in subjects with 
previously treated HER2+ MBC 
• DOR, DCR, PFS, OS 
• Safety: To determine the safety and tolerability 
of BDC-1001 as a single agent and in 
combination with pertuzumab in subjects with 
previously treated HER2+ MBC 
• Incidence of treatment-emergent AEs and SAEs 
graded according to NCI CTCAE v5.0 
• Changes from baseline in vital signs, laboratory 
values, and ECGs 
• PK: To evaluate the exposure profile of 
BDC-1001 as a single agent and in combination 
with pertuzumab in subjects with previously 
treated HER2+ MBC 
• Cmin and Cmax values will be obtained throughout the 
study and compared to the PK data from the Phase 1 
single agent BDC-1001 study utilizing a population 
approach 
• ADA: To evaluate the immunogenicity of 
BDC-1001 as a single agent and in combination 
with pertuzumab in subjects with previously 
treated HER2+ MBC  
• Incidence of ADAs 
Exploratory Objectives 
Exploratory Endpoints 
• To explore potential baseline biomarkers in 
blood and tumor tissue associated with efficacy 
or safety of BDC-1001 as a single agent and in 
combination with pertuzumab in subjects with 
HER2+ MBC 
• Evaluation of BDC-1001 activity in the context of 
additional exploratory predictive and/or prognostic 
biomarkers related to tumor and immune biology by 
such methods as gene expression profiling, 
mutational, protein and tissue image analysis 
• To evaluate exploratory pharmacodynamic 
biomarkers in blood and tumor and their 
association with biological activity, efficacy or 
safety of BDC-1001 as a single agent and in 
combination with pertuzumab in subjects with 
HER2+ MBC 
• Changes in TLR7/8 pathway activation, myeloid and 
T cell content, and activation status by such methods 
as gene expression profiling, protein, and tissue 
image analysis. 
• Evaluation of changes in additional exploratory 
biomarkers in tumor tissue and blood related to tumor 
and immune biology by such methods as gene 
expression profiling, mutational, protein and tissue 
image analysis 
Abbreviations: ADA = anti-BDC-1001 antibody; AE = adverse event; Cmax = maximum (or peak) serum concentration; Cmin = 
minimum (or trough) serum concentration; CTCAE = Common Terminology Criteria for Adverse Events; DCR = disease control 
rate; DOR = duration of response; ECG = electrocardiogram; HER2+ = human epidermal growth factor receptor 2-positive; 
MBC = metastatic breast cancer NCI = National Cancer Institute; OS = overall survival; ORR = objective response rate; PFS = 
progression-free survival; PK = pharmacokinetics; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; 
SAE = serious adverse event; TLR = toll-like receptor 
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3. 
INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design  
This is an open label, Phase 2 study to evaluate preliminary anti-tumor activity, safety, 
tolerability, PK, pharmacodynamics, and immunogenicity of BDC-1001 administered as a single 
agent and in combination with pertuzumab in subjects with HER2+ MBC previously treated with 
trastuzumab deruxtecan (ENHERTU®). 
Eligible subjects will be randomly assigned in a 1:1 ratio to receive BDC-1001 as a single agent 
or BDC-1001 in combination with pertuzumab.  Within each treatment arm, a Simon 2-stage 
design will be applied for enrollment (see Section 8.2). 
Subjects will receive study treatment (ie, BDC-1001 or BDC-1001 in combination with 
pertuzumab) as described in Section 5.2.  To ensure subject safety, dosing of the first 3 subjects 
enrolled in the combination treatment arm will receive study treatment staggered by a minimum 
of 48 hours, and these subjects will be observed for at least 6 hours following the first dose of 
study treatment.  Any subject with acute changes in vital signs will be observed until the events 
have resolved or are stabilized. 
All subjects in both treatment arms will be monitored for AEs and SAEs (Section 8.4.5.1).  Study 
data will be provided to the Safety Review Committee (SRC) for ongoing safety monitoring and 
detection of potential safety concerns (Section 3.1.1). 
Subjects will return to the site for study assessments at the visits listed in the Schedule of 
Assessments.  In the event of study treatment discontinuation, subjects will be asked to complete 
an End of Treatment (EOT) visit (Section 6.25.1), 14 days (± 7 days) after the last dose of study 
treatment (EOT), and then return for a Safety Follow-Up visit (SFU; Section 6.25.2), 28 days 
(+ 7 days) after last treatment.  Subjects who discontinue treatment will have long-term follow-
up (LTFU; Section 6.25.3) every 12 weeks (± 14 days) after last treatment. 
Maintenance Phase:  
As of this protocol Version 3.0 (01 Aug 2024), any subject(s) still receiving study treatment 
(BDC-1001) will transition to the Maintenance Phase and are to be followed as described in 
Table 2. Subjects remaining on study treatment will continue to receive the study drug until a 
criterion for discontinuation has been met (see Section 4.3).  Subjects are to undergo periodic 
safety assessments; the nature and frequency of these assessments are to be performed per local 
standard of care.  It is the Investigator’s responsibility to ensure that subject visits occur 
frequently enough and adequate assessments are performed to ensure subject safety.  
The study clinical database will be closed after the last subject remaining on treatment enters the 
Maintenance Phase.  All data collected prior to implementation of the Maintenance Phase will be 
reported in a clinical study report.  
An overview of the study is displayed in Figure 4. 
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Figure 4: 
Study Schema 
 
Abbreviations: HER2+ = human epidermal growth factor receptor 2-positive; q2w = every 2 weeks; q3w = every 3 weeks;  
R = randomization 
3.1.1. 
Study Oversight 
An SRC, with membership including Investigators or sub-Investigators from sites that have 
enrolled a subject under active investigation, Medical Monitor, and Statistician, or designees, 
will be established to oversee the safety of the study.  The SRC will review safety data, with a 
focus on SAEs and use of the Toxicity Monitoring Safety Stopping Rules (see Section 8.4.5.1).  
The SRC will be responsible for safeguarding the interests of trial subjects and assessing the 
risk:benefit of the study including the safety of the interventions during the trial. 
The SRC will meet periodically based on enrollment, the meeting frequency will be at least 
every 6 months.  Additional meetings may be conducted ad hoc to address additional safety or 
study conduct issues. 
Details of the membership, responsibilities, and procedures of the SRC will be included in an 
SRC Charter. 
3.1.2. 
Number of Subjects 
Approximately 66 evaluable subjects may be enrolled into this study. 
3.1.3. 
Duration of Treatment 
All subjects will be treated for a median duration of approximately 12 months, until disease 
progression according to Response Evaluation Criteria in Solid Tumors version 1.1 
(RECIST v1.1 and iRECIST), unacceptable toxicity, or withdrawal for any reason. Subjects with 
confirmed PD (using the scan at first PD as the new baseline) will be discontinued from study 
treatment; although if a subject is experiencing clinical benefit (is clinically stable), they may 
remain in the study after consultation with the medical monitor.  Clinically stable is defined as 
follows:  
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1. Subject is without worsening symptoms attributable to disease progression,  
2. Subject maintains Eastern Cooperative Oncology Group (ECOG) performance status 
(PS), and 
3. Subject tolerates study treatment (ie, no related SAE or Grade ≥ 3 AE that requires study 
drug discontinuation) per Investigator clinical judgement. 
Maintenance Phase:  
As of this protocol Version 3.0 (01 Aug 2024), any subject still receiving study treatment (BDC-
1001) will transition to the Maintenance Phase and are to be followed as described in Table 2.  
Subjects remaining on study treatment will continue to receive the study drug until a criterion for 
discontinuation has been met (see Section 4.3).  Subjects are to undergo periodic safety 
assessments; the nature and frequency of these assessments are to be performed per local 
standard of care.  It is the Investigator’s responsibility to ensure that subject visits occur 
frequently enough and adequate assessments are performed to ensure subject safety.  
3.1.4. 
Duration of Study 
The planned overall study duration is approximately 4 years. 
The definition of the end of the study is when the last subject has completed their SFU.  The 
Sponsor or regulatory authorities may terminate the study at any time at their discretion.  
3.2. 
Rationale for Study Design, Dose Selection, and Study Population  
3.2.1. 
Rationale for Study Design 
This is an open-label, Phase 2 study of BDC-1001 as single agent and in combination with 
pertuzumab to evaluate the preliminary anti-tumor activity, safety, tolerability, PK, 
pharmacodynamics, and immunogenicity of BDC-1001 administered as single agent and in 
combination with pertuzumab in subjects with HER2+ MBC previously treated with trastuzumab 
deruxtecan (ENHERTU®).  
The target dose and regimen of BDC-1001 for this study is 20 mg/kg q2w.  This target dose and 
regimen are well tolerated as a single agent (see Section 1.2.1.2 for details).   
Pertuzumab will be given at the approved dose (840 mg on Week 1, followed by 420 mg q3w 
thereafter). 
Bayesian toxicity monitoring will be used to monitor treatment related SAE rates to ensure 
subject safety (Section 8.4.5.1). 
3.2.2. 
Rationale for Selection of BDC-1001 Recommended Dose 
The dose and regimen of BDC-1001 for this study will be the RP2D of BDC-1001 of 20 mg/kg 
q2w, as determined in the ongoing FIH study BBI-20201001 [NCT04278144].  BDC-1001 will 
be administered in combination with the approved dose of pertuzumab (described above).   
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This starting dose for BDC-1001 is based on the dose escalation phase of Study BBI-20201001, 
which enrolled subjects with a wide range of HER2-expressing solid tumor types, including 
tumor types to be evaluated in the dose expansion phase.  The evaluated dosing levels and dosing 
frequencies ranged from 0.15 mg/kg up to 20 mg/kg and q1w, q2w, and q3w, respectively, to 
assess safety, tolerability, and clinical activity to determine the RP2D.  
As of 23 January 2024, no clinically meaningful differences in the safety profile of BDC-1001 
monotherapy were observed across the different dosing levels and dosing frequencies tested 
regarding the percentage of subjects requiring dose interruptions, dose reductions, and drug 
discontinuations for AEs, as well as the percentage of subjects with SAEs (Section 1.2.1.2).  
BDC-1001 monotherapy is well tolerated and no safety signals or trends could be observed.  
Therefore, from a safety and tolerability perspective, these doses and regimens are considered 
acceptable for further evaluation. 
The most clinically meaningful efficacy was observed at a dose of BDC-1001 20 mg/kg q2w. 
Among 7 subjects treated with BDC-1001 20 mg/kg q2w monotherapy, 1 CR (14%), 1 PR (14%) 
and 3 SDs (43%) were observed (Li et al, 2023b). 
Population PK results confirmed linear PK characteristics of BDC-1001 at 5 mg/kg q3w and 
above, with population mean clearance of 1.6 L/day and median terminal half-life of 4.3 days 
(range: 1.2-12).  The population mean volume of central distributional compartment was 
estimated to be 4.3 liters, which is close to the physiological volume of serum/plasma in humans 
(~3.5 liters); the volume of peripheral distributional compartment was estimated to be 2.6 liters; 
together, these estimates suggest BDC-1001 distribution in humans is consistent with the 
conventional knowledge that mAb therapeutics distribute primarily within the vascular space, 
with modest extravasation into the peripheral tissues.  At 20 mg/kg q2w monotherapy, where 
most clinically meaningful efficacy was observed, the median steady-state trough serum 
concentration (Cmin) of BDC-1001 has reached or exceeded 10 µg/mL, which was the Cmin level 
in the preclinical xenograft model where significant regression of tumors was observed. 
 
 
 
 
 
 
  
 
 
 
 
 
 
   
Exposure-response of BDC-1001 demonstrated a positive association between anti-tumor 
activity and Cmin, peak serum concentration (Cmax), and area under the concentration-time curve 
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(AUC) in the BDC-1001 q2w treated subjects.  However, this positive association was not 
observed for subjects treated with BDC-1001 q3w and was weaker in q1w subjects.  At 
20 mg/kg q2w, where most clinically meaningful efficacy was observed, the median steady-state 
Cmin of BDC-1001 has reached or exceeded 10 µg/mL, which was the Cmin level in the preclinical 
xenograft model where significant regression of tumors was observed.   
The results from the dose escalation phase of Study BBI-20201001 support BDC-1001 20 mg/kg 
q2w as a dose for further evaluation. 
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4. 
SELECTION OF STUDY POPULATION 
Potential subjects must sign an informed consent form (ICF) before any study specific screening 
tests may be conducted.  
Screening tests are described in Section 6.1.  
4.1. 
Inclusion Criteria 
Subjects must meet all of the following criteria to be eligible for enrollment in the study: 
1. Be able to understand and sign the informed consent form 
2. Be age 18 years or older at the time of informed consent 
3. All subjects must agree to have a biopsy prior to enrollment.  If, in the judgement of the 
Investigator, a biopsy is not safely accessible or clinically feasible an archival tumor 
tissue sample must be submitted in lieu of a freshly collected specimen 
4. Histologically confirmed adenocarcinoma of the breast that is HER2+ (per 2018 
ASCO/CAP HER2 testing guidelines) by Clinical Laboratory Improvement Amendments 
(CLIA) certified laboratory assessment  
5. Have received 2 or more prior lines of anti-HER2-directed therapies, at least 1 of them is 
in the metastatic setting and 1 of the prior therapies needs to be trastuzumab deruxtecan 
(ENHERTU®).  Prior neo-adjuvant or adjuvant therapy that resulted in relapse within 
12 months of completion of therapy will be considered a line of treatment for metastatic 
disease 
6. Have experienced disease progression on or been otherwise unsuitable for (eg, did not 
tolerate) the most recent therapy  
7. Have measurable disease according to RECIST v1.1 criteria 
8. Have ECOG PS of 0 or 1 
9. Have life expectancy of greater than 12 weeks per the Investigator 
10. Adequate organ function defined as follows: 
a. Hematology: 
i. 
Absolute neutrophil count ≥ 1500 cells/mm3 
ii. 
Platelet count ≥ 75,000 cells/mm3  
iii. 
Hemoglobin ≥ 9 g/dL (and without transfusion within 7 days) 
b. Renal: 
i. 
Creatinine clearance ≥ 30 mL/min on the basis of the Cockcroft-Gault glomerular 
filtration rate estimation:  
[(140-age) × (weight in kg) × (0.85 if female)] / [72 × (serum creatinine 
in mg/dL)] 
c. Coagulation: 
i. 
International normalized ratio (INR) and prothrombin time (PT) ≤ 1.5 × ULN 
unless receiving anticoagulation therapy 
ii. 
Activated partial thromboplastin time (aPTT) only needs to be assessed if 
evaluated per standard of care.  If evaluated, aPTT ≤ 1.5 × upper limit of normal 
(ULN), unless undergoing anticoagulation therapy 
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d. Hepatic: 
i. 
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
≤ 3 × ULN (or ≤ 5 × ULN in subjects with known hepatic metastases) 
ii. 
Total bilirubin ≤ 1.5 × ULN (isolated value > 1.5 × ULN is acceptable if direct 
bilirubin is <35%) 
11. Women of childbearing potential should agree to not donate eggs and must use a highly 
effective contraceptive measure (a method that can achieve a failure rate of less than 1% 
per year) during treatment and until 7 months after the end treatment.  Highly effective, 
alternative non-hormonal contraceptive measures are preferred, include the following: 
a. Intrauterine device  
b. Vasectomized partner  
c. Sexual abstinence  
d. Bilateral tubal occlusion  
12. Potent men that are partners of women of childbearing potential must be willing to use 
condoms in combination with a second highly effective method of female contraception 
(as above) during the study and agree not to donate sperm from Screening through 
7 months after completion of study.  A male partner will be considered as potent unless 
surgically sterilized (with documentation of sterility). 
4.2. 
Exclusion Criteria 
A subject must not meet any of the following criteria to be eligible for this study: 
1. Central nervous system metastases with the exception of disease that is asymptomatic, 
clinically stable (without evidence of progression for at least 4 weeks confirmed by 
imaging during study Screening), and has not required steroids for at least 28 days before 
starting study treatment 
2. Cardiac disease including the following: 
a. Congestive heart failure (New York Heart Association classes II–IV) 
b. Left ventricular ejection fraction (LVEF) < 50% by echocardiogram (ECHO) or 
multi-gated acquisition (MUGA) scan 
c. QT corrected - Fridericia's correction formula (QTcF) prolongation of 
> 480 milliseconds (ms) based on a 12-lead electrocardiogram (ECG)  
d. Serious or uncontrolled cardiac arrhythmia within 6 months before starting study 
treatment 
e. Myocardial infarction, unstable angina pectoris, or coronary angioplasty, stenting, or 
surgery within 6 months before starting study treatment 
f. Serious or uncontrolled hypertension (≥ 180 mmHg systolic or ≥ 120 mmHg 
diastolic) within 6 months before starting study treatment 
g. Pericarditis or pericardial effusion that is symptomatic within 6 months before 
starting study treatment 
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3. Pulmonary disease including idiopathic pulmonary fibrosis, interstitial lung disease, 
pneumonitis requiring steroids, or symptomatic pleural effusion within 6 months before 
starting study treatment OR ongoing requirement for supplemental oxygen 
4. Hepatic disease resulting in symptomatic ascites, encephalopathy, coagulopathy, 
esophageal/gastric varices, or persistent jaundice 
5. Arterial thrombotic event, stroke, or transient ischemia attack within 6 months before 
starting study treatment 
6. Bleeding diathesis or uncontrolled bleeding within 7 days before starting study treatment 
7. Bone marrow transplant or solid organ transplant 
8. Infection including the following: 
a. Infection requiring systemic therapy within 7 days before starting study treatment 
b. Active human immunodeficiency virus (HIV) as defined by the protocol 
(Section 6.14.3) 
c. Positive hepatitis B surface antigen test at Screening or within 3 months of starting 
study treatment, a subject whose hepatitis B surface antigen (HBsAg) is negative and 
hepatitis B core antibody (HBcAb) is positive may be enrolled if a hepatitis B virus 
(HBV) DNA test is negative and either the subject is treated with potent antiviral 
therapy or is retested for HBsAg and HBV DNA every month 
d. Positive hepatitis C antibody test and confirmatory ribonucleic acid (RNA) test at 
Screening or within 3 months of starting study treatment.  Exceptions include subjects 
that (1) have hepatitis C virus (HCV) viral load below the assay limit-of-quantitation 
and (2) completed curative antiviral therapy or are compliant with ongoing antiviral 
therapy 
9. Autoimmune disease requiring systemic disease-modifying or immunosuppressive 
therapy within 2 years before starting study treatment.  Exceptions include disease 
managed with only replacement therapies (eg, thyroxine, etc.) 
10. Malignancy within 2 years before starting study treatment other than the disease under 
study.  Exceptions include indolent or definitively treated disease not expected to require 
treatment during the study, affect the safety of subjects, or affect the endpoints of the trial 
11. Any medical condition requiring corticosteroids (> 10 mg daily oral prednisone or 
equivalent) or other systemic immunosuppressive therapy within 28 days before starting 
study treatment.  Exceptions include inhaled or topical steroids 
12. Residual toxicity from previous treatment including the following: 
a. Toxicity related to prior treatment not resolved to Grade ≤ 1 
Exceptions to the above criterion include toxicities that do not pose a risk to vital 
organ systems (eg, alopecia, etc.) or toxicities that are stable as managed by 
replacement therapies (eg, hypothyroidism, etc.) 
13. Prior anticancer therapies including: 
a. Small molecule TLR7/8 agonist or TLR7/8 agonist that has been conjugated to 
tumor-targeting antibody such as ISACs within 12 months before starting study 
treatment 
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b. An investigational agent or anticancer therapy within 28 days before starting study 
treatment or within 5 estimated elimination half-lives, whichever is shorter.  
Gonadotropin-releasing hormone agonists for ovarian suppression in premenopausal 
women are permitted 
14. History of severe hypersensitivity to any ingredient of BDC-1001 or pertuzumab 
15. Received live/attenuated virus vaccine within 28 days before starting study treatment 
16. Major surgery within 28 days of starting study treatment 
17. Radiation therapy within 2 weeks of C1D1 
18. Actively enrolled in another clinical study, unless it is an observational 
(noninterventional) clinical study or the follow-up component of an interventional study 
19. Subject is a lactating mother or pregnant as confirmed by pregnancy tests within 48 hours 
prior to start of study treatment 
20. Subject is unwilling or unable to follow protocol requirements 
21. Recurrent ascites requiring routine intervention >Q3 months 
22. Any condition that, in the opinion of the Investigator, would interfere with evaluation of 
BDC-1001 and pertuzumab or interpretation of the subject’s safety or study results 
4.3. 
Subject Discontinuation 
Subjects may withdraw from study treatment or from the study at any time, for any reason.  
Subjects who withdraw from treatment should be encouraged to complete the SFU visit (see 
Schedule of Assessments – Maintenance Phase [Table 2]).  
If a subject withdraws consent from participation, the Investigator should make reasonable 
efforts to document the reason(s) for withdrawal of consent, while fully respecting the subject’s 
rights.  
If a subject is discontinued from the study for any other reason, the primary reason for 
discontinuation must be recorded in the subject’s source documents. 
4.3.1. 
Removal of Subjects from the Treatment or Study 
Subjects may be removed from study treatment at any time without the subject’s consent if the 
Investigator or Sponsor determines that it is not in the best interest of the subject to continue 
participation. 
A subject will be discontinued from the study for any of the following reasons: 
• 
A female subject has a pregnancy that is confirmed  
• 
Sponsor or regulatory authorities close the study  
A subject may be discontinued from the study, after discussion between the Investigator, 
Sponsor, and the Medical Monitor for any of the following reasons: 
• 
A subject develops a life-threatening SAE that puts them at significant risk.  
• 
A subject has a prolonged interruption of study treatment (> 6 weeks from planned 
dose) or holding of BDC-1001 for > 12 weeks if due to a treatment-related AE, unless 
continued treatment is approved by the Medical Monitor.  Note: subjects will be 
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withdrawn from study treatment if an immune-related toxicity does not resolve to 
Grade 1 or baseline within 12 weeks of study drug interruption. 
• 
A subject is noncompliant with study requirements.  
If a subject is discontinued due to an AE or pregnancy, the Sponsor must also be notified within 
24 hours, as appropriate. 
If a subject discontinues due to an AE or other medical reason, the subject must continue to be 
followed at regular intervals until the AE normalizes, is determined to be chronic by the 
Investigator, or returns to the subject’s baseline condition.  Additional follow-up schedule for 
these subjects will be made on an individual basis by the Sponsor and the Investigator together. 
The visit schedule for follow-up after discontinuation is described in the Schedule of 
Assessments. 
4.3.2. 
Lost to Follow-Up 
Subjects will be considered as lost to follow-up if they miss 3 consecutive study contacts 
(telephone calls and/or clinic visits). 
4.3.3. 
Replacement of Subjects 
Subjects that discontinue study treatment before their first radiographic tumor assessment 
(minimum of 4 weeks after C1D1) will be replaced. 
4.4. 
Method of Assigning Subjects 
This is an open-label study that will be randomized as described in Section 4.5. 
Subjects will be considered enrolled once the Investigator or designee completes assessment of 
subject eligibility and confirms that the subject meets all inclusion and exclusion criteria for the 
trial. 
4.5. 
Randomization Procedures 
Eligible subjects will be randomly assigned to treatment according to Interactive Response 
Technology, in a 1:1 ratio to receive BDC-1001 as a single agent or in combination with 
pertuzumab. 
Eligible subjects will be randomly assigned in a 1:1 ratio to receive BDC-1001 as a single agent 
or BDC-1001 in combination with pertuzumab.   
4.5.1. 
Blinding 
There will be no blinding used in this study. 
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5. 
ENROLLMENT PROCEDURES 
5.1. 
Method of Assigning Subjects 
This is an open-label study that will be randomized as described in Section 4.5. 
Subjects will be considered enrolled once the Investigator or designee completes assessment of 
subject eligibility and confirms that the subject meets all inclusion and exclusion criteria for the 
trial.  
5.1.1. 
Description of BDC-1001 
  
 
 
 
5.1.2. 
Description of Pertuzumab 
The pertuzumab dosage form is a sterile, clear to slightly opalescent, colorless to pale brown 
liquid for intravenous (IV) infusion.  Each single-dose vial contains 420 mg of pertuzumab 
(14.0 mL/vial) at a concentration of 30 mg/mL in 20 mM L-histidine acetate, 120 mM sucrose 
and 0.02% polysorbate 20 at pH 6.0.   
5.1.3. 
Preparation/Handling/Storage/Accountability  
Refer to the current Pharmacy Manual. 
5.1.3.1. 
Labelling and Packaging 
Refer to the current Pharmacy Manual. 
5.1.3.2. 
Storage and Stability 
BDC-1001 drug product should be stored in accordance with the current Pharmacy Manual. 
Pertuzumab should be stored in accordance with the current pertuzumab Investigator’s Brochure 
and the current Pharmacy Manual. 
5.1.3.3. 
Acquisition and Accountability 
Refer to the current Pharmacy Manual. 
5.1.3.4. 
Return of BDC-1001 and Pertuzumab 
Refer to the current Pharmacy Manual. 
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5.2. 
Dosing and Administration 
BDC-1001 will be administered either as a single agent or in combination with pertuzumab. In 
the combination arm, treatment for the first 3 subjects will be staggered by a minimum of 
48 hours.  The 3 subjects will be observed for at least 6 hours after the first dose of study 
treatment.  Subjects with acute changes in vital signs will be observed until the events have 
resolved or stabilized.  Please note that no observation period is required after administration of 
study drugs except in the first dose for the first 3 subjects in the combination arm.  
5.2.1. 
Premedication 
All subjects should be premedicated prior to administration of BDC-1001 for potential IRRs with 
paracetamol and diphenhydramine (eg, 1000 mg paracetamol, 50 mg diphenhydramine) or 
according to institutional standards. 
On dosing days when pertuzumab is administered without BDC-1001, premedication for 
pertuzumab is only required if a subject experiences IRR during the previous dose. 
Corticosteroids and other immunomodulators remain excluded for study treatment infusions. 
5.2.2. 
BDC-1001 Administration 
BDC-1001 will be administered q2w at a dose of 20 mg/kg IV by infusion pump over 60 minutes 
(± 15 minutes).  BDC-1001 will be administered before pertuzumab on days that both BDC-1001 
and pertuzumab are administered. 
Vital signs must be assessed prior to administration of BDC-1001.  Subjects that have any 
persistent low-grade IRR may prolong the infusion time to 90-120 minutes (including flushing 
time).  
Refer to the current Pharmacy Manual for specific instructions for the storage and preparation 
and administration of BDC-1001. 
5.2.3. 
Pertuzumab Administration 
Pertuzumab will be administered as an IV infusion according to the package insert (ie, initial 
dose of 840 mg over 60 minutes followed every 3 weeks by a dose of 420 mg over 30 to 
60 minutes).  On days that both BDC-1001 and pertuzumab are administered, pertuzumab will be 
administered 30 to 60 minutes after the end of BDC-1001 infusion. 
Refer to the current Pharmacy Manual for specific instructions for the storage and preparation 
and administration of pertuzumab.  
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5.2.4. 
Dose Modifications 
5.2.4.1. 
Dose Interruptions 
BDC-1001 and/or pertuzumab may be interrupted at the discretion of the Investigator for up to 
1 cycle (6 weeks for reasons other than a treatment-related AE) from the planned date of 
administration.  Treatment may be held for up to 12 weeks after a treatment-related AE, unless 
continued treatment is approved by the Medical Monitor.  In the combination arm, pertuzumab 
must be administered in combination with BDC-1001, not as a single agent. Thus, both 
BDC-1001 and pertuzumab treatment must be interrupted in a subject who receives combination 
treatment when BDC-1001 treatment interruption is warranted.  
If a subject is assessed as requiring a dose delay longer than 6 weeks, the subject may be 
withdrawn from study treatment (Section 4.3.1).  After a 6-week interruption, study treatment 
may be resumed if the Investigator and Sponsor agree that it is in the best interest of the subject.  
Pertuzumab may be restarted according to the package insert (ie, initial dose of 840 mg over 60 
minutes followed every 3 weeks by a dose of 420 mg over 30 to 60 minutes).  BDC-1001 and/or 
pertuzumab may be held for up to 12 weeks if due to a treatment-related AE, unless continued 
treatment is approved by the Medical Monitor.  The Investigator may consider dose interruptions 
or discontinuation of BDC-1001 based on other events not listed in Table 4 according to clinical 
judgement, in consultation with the Medical Monitor. 
Table 4: 
BDC-1001 Dose Interruption and Resumption Parameters 
Toxicities 
Dose Interruption Criteria 
(within 3 days before 
administration) 
Dose Resumption Rules 
Infusion-Related Reactions 
Refer to Section 5.3 and Appendix A 
Immune-Related Events 
Refer to Section 5.3.2 
Cardiac Toxicity 
Refer to Section 5.3.3 
All other non-hematological 
toxicities 
• NCI-CTCAE v5.0 Grade ≥ 3  
• Grade ≥ 3 fatigue lasting 
≥ 48 hours 
• Grade 3 electrolyte abnormality 
with clinical symptoms or 
lasting ≥ 48 hours 
• Grade 3 nausea/vomiting or 
diarrhea lasting ≥ 48 hours with 
adequate antiemetic and other 
supportive 
Resolved to Grade 1 or baseline 
values 
Hematological laboratory 
abnormalities 
• Febrile neutropenia 
• Grade 4 thrombocytopenia, 
Grade 3 with bleeding  
• NCI-CTCAE v5.0 Grade ≥ 3; 
the treatment interruption with 
BDC-1001 will be at the 
discretion of the Investigator. 
Treatment with BDC-1001 will be 
resumed at the discretion of the 
Investigator 
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Abbreviations: CTCAE = Common Terminology Criteria for Adverse Events; DLT = dose-limiting toxicity; NCI = 
National Cancer Institute 
5.2.4.2. 
BDC-1001 Dose Reductions 
No intrasubject dose escalations or reductions are permitted for BDC-1001.  
5.2.4.3. 
Pertuzumab Dose Reductions 
No intrasubject dose escalations or reductions are permitted for pertuzumab.  
5.3. 
Management of Specific Safety Concerns 
5.3.1. 
Infusion-Related Reactions 
All subjects should be premedicated for potential IRRs as described in Section 5.2.1. 
If an IRR is observed during BDC-1001 administration, the infusion rate should be reduced 
(infusion duration may increase to 120 minutes) or the infusion should be interrupted or 
discontinued based on the symptoms.  The management of IRR is summarized in Appendix A.  
Any medications used to treat Grade 1 or 2 IRR may be continued for subsequent infusions per 
institutional protocol. 
Corticosteroids and other immunomodulators remain excluded as prophylactic medication.  
Additional details on allowable concomitant medications are provided in Section 5.4. 
Prophylactic or supportive treatment of study treatment-induced AEs will be otherwise as per 
Investigator’s discretion and institutional guidelines. 
Refer to the pertuzumab Investigator’s Brochure for safety management recommendations of 
pertuzumab-related IRRs. 
5.3.2. 
Immune-Related Events 
For guideline on diagnosis, monitoring, and management of immune-related toxicity, please refer 
the following additional assessments and National Comprehensive Cancer Network Guidelines-
Management of Immunotherapy-Related Toxicities (Thompson et al, 2023): 
• 
Observation of immune-related clinical signs and symptoms 
• 
Thyroid-stimulating hormone (TSH)/ triiodothyronine (T3)/ thyroxine (T4)  
• 
Pulse oximetry at every cycle 
Dosing adjustments will be made for BDC-1001 as described in Table 5.  Subjects may continue 
pertuzumab treatment pending approval from the Medical Monitor. 
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Table 5: 
Dose Modifications Guidelines for BDC-1001 and Pertuzumab 
Immune-Related 
Adverse Reactions 
Severity 
Treatment Modification 
Pneumonitis  
Grade 2  
Withhold until adverse reactions recover 
to Grade 1 or baseline a  
Grade 3 or 4, or recurrent Grade 2  
Permanently discontinue  
Colitis 
Grade 2 or 3  
Withhold until adverse reactions recover 
to Grade 1 or baseline a  
Grade 4 or recurrent Grade 3  
Permanently discontinue  
Nephritis 
Grade 2 with creatinine > 1.5 to ≤ 3 times 
ULN 
Withhold until adverse reactions recover 
to Grade 1 or baseline a  
Grade ≥ 3 with creatinine > 3 times ULN 
Permanently discontinue 
Endocrinopathies 
• Symptomatic hypophysitis, Type 1 
diabetes associated with Grade ≥ 3 
hyperglycemia (glucose > 250 mg/dL 
or > 13.9 mmol/L) or associated with 
ketoacidosis  
• Hyperthyroidism Grade ≥ 3 
• Withhold until adverse reactions 
recover to Grade 1 or baseline a  
• For subjects with Grade 3 or Grade 4 
endocrinopathy that improved to 
Grade 2 or lower and is controlled with 
hormone replacement, if indicated.  
Otherwise, treatment should be 
discontinued. 
• Hypothyroidism may be managed with 
replacement therapy without treatment 
interruption. 
Hepatitis 
Grade 2 with AST or ALT > 3 to 5 times 
ULN or total bilirubin > 1.5 to 3 times 
ULN  
Withhold until adverse reactions recover 
to Grade 1 or baseline a 
Grade ≥ 3 with AST or ALT > 5 times 
ULN or total bilirubin > 3 times ULN 
Permanently discontinue 
In subjects with liver metastasis and 
elevated LFTs, Grade 2 AST or ALT 
> 3 to 5 times baseline, or total 
bilirubin > 1.5 to 3 times baseline 
Permanently discontinue 
Skin reactions 
Grade 3 or suspected SJS or TEN 
Withhold until adverse reactions recover 
to Grade 1 or baseline a 
Grade 4 or confirmed SJS or TEN 
Permanently discontinue 
Other immune-
related adverse 
reactions 
• Based on severity and type of reaction 
(Grade 2 or Grade 3) 
Withhold until adverse reactions recover 
to Grade 1 or baseline a 
• Grade 3 or 4 myocarditis 
• Grade 3 or 4 encephalitis 
• Grade 3 or 4 Guillain-Barré syndrome  
• Grade 4 or recurrent Grade 3 
Permanently discontinue 
Infusion-related 
reactions 
Grade 3 or 4  
Permanently discontinue 
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; LFTs=liver function transferases; 
SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; ULN = upper limit of normal 
Note: Toxicity grades follow the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 
(NCI-CTCAE v5.0). 
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a 
If treatment-related toxicity does not resolve to Grade 1 or baseline within 12 weeks after last dose, or if corticosteroid dosing 
cannot be reduced to ≤ 10 mg prednisone or equivalent per day within 12 weeks, all therapies should be permanently 
discontinued.  
All therapies should be permanently discontinued for Grade 4 or ≥ 1 recurrence of Grade 3 
immune-related adverse reactions, unless otherwise specified in Table 5.  
5.3.3. 
Cardiac Toxicity 
Decreases in LVEF have been reported with drugs that block HER2 activity, and subjects who 
have received prior anthracyclines or prior radiotherapy to the chest area may be at higher risk of 
a LVEF decrease.  Changes in LVEF should be managed with the actions outlined in Table 6.  
To monitor for potential anti-HER2 related toxicities the following additional assessments will 
be performed at baseline and regularly throughout the study in accordance with the Schedule of 
Assessments: 
• 
ECG 
• 
ECHO or MUGA tests.  These assessments will be performed at screening, 6 weeks 
after the first study treatment, then every 3 months thereafter during treatment if no 
abnormal findings are noted.  In the presence of symptoms, monitoring should begin 
immediately. 
Table 6: 
Management of LVEF Changes (Based on Absolute Changes) 
Symptomatic 
CHF 
LVEF < 45%  
LVEF  45% to 49% and 
Decrease is ≥ 10% From 
Baseline 
LVEF > 49% or > 45% 
and Decrease is < 10% 
from Baseline 
Discontinue 
study treatment 
Interrupt study treatment 
dosing. 
Repeat LVEF assessment 
within 3 weeks. 
Interrupt study treatment 
dosing. 
Repeat LVEF assessment 
within 3 weeks. 
Continue study treatment. 
Abbreviations: CHF = congestive heart failure; LVEF = left ventricular ejection fraction 
Note: LVEF decreases are all in absolute percentages. 
Study treatment may be resumed if the LVEF has recovered to greater than 49%, or to 45% to 
49% associated with less than a 10% absolute decrease below pretreatment values.  
If after a repeat assessment within approximately 3 weeks, the LVEF has not improved, or has 
declined further, study treatment should be discontinued, unless the Investigator deems that the 
benefits for the individual subject outweigh the risks and with the approval from Medical 
Monitor. 
5.3.4. 
Cytokine Release Syndrome 
Although cytokine release syndrome (CRS) has not been observed to date in preclinical studies, 
3 subjects had Grade 1 CRS that was related to treatment in the ongoing study BBI-20201001.  
One subject received 12 mg/kg BDC-1001 in the monotherapy arm and 2 subjects received 
20 mg/kg in the expansion arm.  Data from experimental clinical studies of other 
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immune-modulating agents have demonstrated potential CRS events.  Therefore, guidelines for 
the grading and management of CRS have been provided in Appendix B. 
5.4. 
Prior and Concomitant Medications 
5.4.1. 
Recording of Use of Concomitant Medications 
The Investigator or qualified designee will review prior medication use and will record them in 
the electronic case report form (eCRF).  Concomitant medications will be recorded in accordance 
with the Schedule of Assessments.  
5.4.2. 
Prohibited Concomitant Therapy 
Prohibited prior and concomitant medications are excluded in accordance with the eligibility 
criteria (Section 4) except as necessary to manage AEs.  Subjects are not allowed to receive 
concomitant therapies as described in Sections 5.4.2.1 and 5.4.2.2. 
5.4.2.1. 
Anti-Cancer Therapy 
The following anticancer medications and treatments are prohibited during the study: 
• 
Any concurrent, systemic anti-neoplastic therapy (ie, chemotherapy, immunotherapy, 
or standard or investigational agents for treatment of advanced HER2-expressing 
solid tumors) other than BDC-1001 and pertuzumab as specified in this protocol. 
• 
Any non-palliative radiation therapy.  Radiation therapy administered with palliative 
intent (ie, for pain, bleeding, spinal cord compression, brain metastasis, new or 
impending pathologic fracture, superior vena-cava syndrome, or obstruction) is 
permitted for non-target lesions. During irradiation, study treatment will be 
interrupted and resumption will be discussed with the medical monitor. 
• 
Any complementary medications (eg, herbal supplements or traditional Chinese 
medicines) intended to treat the disease under study. 
5.4.2.2. 
Immunomodulatory Therapy 
Subjects should not be using immunomodulating agents, including, but not limited to, steroids, 
TNFα inhibitors, cyclophosphamide, methotrexate, azathioprine, and thalidomide.  
Systemic corticosteroids, IL-6, and TNFα inhibitors may be administered in the treatment of AEs 
at the judgement of the Investigator after consultation with the Medical Monitor.  
Low-dose glucocorticoids up to 10 mg per day prednisone or equivalent are allowed.  The use of 
inhaled corticosteroids and mineralocorticoids (eg, fludrocortisone) for subjects with orthostatic 
hypotension or adrenocortical insufficiency is allowed.  Megestrol administered as appetite 
stimulant is acceptable while the subject is enrolled in the study.  
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5.5. 
Study Treatment Compliance 
All study treatment will be administered at the study site. 
At each study visit, the subject should be reminded of the significance of returning to the study 
site for the next scheduled visit.  Attendance and assessments will be recorded in the eCRF.  
5.5.1. 
Concomitant Medications 
All subjects should be premedicated for potential IRRs as described in Section 5.2.1.  Subjects 
should not be premedicated with corticosteroids or immunomodulators. 
Subjects who experience infusion-associated symptoms may be treated symptomatically with 
ibuprofen, diphenhydramine, acetaminophen, and/or cimetidine or other H2 receptor antagonists, 
as per standard practice.  Serious infusion-associated events should be managed with supportive 
therapies as clinically indicated (such as supplemental oxygen and E2 adrenergic agonists).  
Systemic corticosteroids may be administered at the discretion of the Investigator for the 
management of AEs.  
Gonadotropin-releasing hormone agonists for ovarian suppression in premenopausal women are 
permitted. 
Approved COVID-19 vaccines are allowed but should be administered at least 72 hours prior to 
any BDC-1001 treatment and not on the day of treatment.  All other inactivated vaccines are 
allowed at any time, except on the day of treatment.  Live/attenuated vaccines are not allowed at 
any time during treatment. 
5.6. 
Discontinuation of Study Treatment / Withdrawal from Study 
Subjects will be advised that they are free to discontinue study treatment or withdraw from the 
study at any time.  Treatment beyond disease progression will be allowed with the approval of 
the Sponsor, provided the subject is clinically stable (Section 3.1.3).  Discontinuation of study 
treatment allows further study assessments to be collected.  Withdrawal from the study results in 
no further collection of assessments.  
An individual subject may discontinue from study treatment or withdraw from the study for any 
of the following reasons: 
• 
Completed dosing as specified in the protocol 
• 
Radiological progression per RECIST v 1.1 
• 
Clinical progression 
• 
AE 
• 
Physician decision 
• 
Lost to follow-up 
• 
Study terminated by sponsor 
• 
Death 
• 
Protocol deviation 
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• 
Pregnancy 
• 
Withdrawal of consent 
• 
Patient decision 
6. 
STUDY ASSESSMENTS AND PROCEDURES 
Descriptions of assessments and related guidance/instructions are provided in the sections below. 
All assessments and procedures should be conducted in accordance with the Schedule of 
Assessments.  
Additional guidance for study assessments and procedures is provided in the following 
appendices and the current pertuzumab Investigator’s Brochure:  
• 
Appendix A - Infusion Reaction Guideline  
• 
Appendix B - Management of Cytokine Release Syndrome  
• 
Appendix C - RECIST v1.1 Criteria for Tumor Response 
• 
 
 
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• 
Appendix D - iRECIST Criteria for Tumor Response 
• 
Appendix E- Statistical Consideration for Defining Date of iRECIST PD 
In the Maintenance Phase, study assessments and procedures will be performed per local 
standard of care.  See Table 2 for schedule and procedures. 
6.1. 
Screening Period and Enrollment Description  
A signed and dated ICF must be obtained before any study-related procedures or assessments are 
conducted.  
All subjects will be screened for eligibility to participate in the study.  Screening assessments are 
outlined in the Schedule of Assessments.  The Screening Period is up to 28 days prior to C1D1, 
beginning with the day informed consent is obtained.  If subjects need to be rescreened, a limited 
set of Screening tests may be used by the Investigator in consultation with the Medical Monitor.  
If Screening assessments are performed on Study Day 1, they can be considered to be Day 1 data 
and there is no need to repeat them. 
6.2. 
Informed Consent 
The subject’s written informed consent must be obtained prior to his/her participation in the 
study and should be documented in the subject’s medical records.  Additional guidance and 
information regarding informed consent is provided in Section 9.1.2. 
6.3. 
Eligibility Criteria Review  
Eligibility criteria (inclusion criteria [Section 4.1] and exclusion criteria [Section 4.2]), will be 
checked during the Screening Period and will be confirmed on Day 1 before the initial study 
drug treatment. Assessments will include laboratory results, ECGs, and other assessments to 
meet protocol eligibility requirements.  
6.4. 
Physical Examination, Weight, and Height  
A physical examination will be assessed in accordance with the Schedule of Assessments.  A full 
physical examination is required at Screening.  All other physical examinations can be 
symptom-directed.  Physical examinations, including ECOG PS, will include evaluation of the 
body systems/organs: general appearance; dermatological; head and eyes; ears, nose, mouth, and 
throat; neck, thyroid, pulmonary; cardiovascular; abdominal; gastrointestinal, genitourinary 
(optional); lymphatic; extremities; musculoskeletal/extremities; neurological and psychiatric.   
Weight and height will also be recorded in kilograms and centimeters, respectively. 
6.5. 
Study Treatment Administration 
Study treatment should be administered as directed in Section 5.2, and at the days and times 
outlined in the Schedule of Assessments. 
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6.6. 
Medical History and Demographics 
The subject’s medical history and demographic information will be obtained by the Investigator 
or qualified designee during the Screening Period.  
Demographic information includes age, gender, and self-reported race/ethnicity. 
Medical history includes clinically significant diseases, surgeries, cancer history (including prior 
cancer therapies and procedures, as well as classification by origin, tissue type, grade, stage, 
markers, and mutations if available), reproductive status, medications (including over-the-
counter or prescription medicines, vitamins, and/or herbal supplements) taken within 14 days 
prior to planned first dose administration must be recorded in the eCRF, and all active conditions 
or any condition diagnosed within the prior 10 years that are considered to be clinically 
significant by the Investigator.  Substance use will also be recorded.   
Tumor history, including, but not limited to, results of tumor mutational burden, programmed 
death ligand 1 (by immunohistochemistry), actional genomic mutations such as HER2 
amplification/mutation, PIK3CA mutation, etc., and microsatellite stability/instability testing 
should be recorded, if known. 
6.7. 
ECOG Performance Status 
ECOG PS will be assessed in accordance with the Schedule of Assessments and will be assessed 
using the grading scale shown in Table 7.  
Table 7: 
ECOG Performance Status 
ECOG Grade 
Description 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light housework, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities.  Up and 
about more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled. Cannot carry on any selfcare.  Totally confined to bed or chair 
5 
Dead 
Abbreviations: ECOG = Eastern Cooperative Oncology Group 
Source: (Oken et al. 1982) 
6.8. 
Vital Signs 
Vital signs will be measured in accordance with the Schedule of Assessments.  These 
assessments include respiratory rate, pulse rate, body temperature, and systolic and diastolic 
blood pressure while the subject is in a supine or seated position.  
The timing of pre- and post-infusion vital sign and ECG collections is presented in Table 8.  For 
subjects with clinically normal ECGs, measurements are not required after Cycle 2 for EOI 
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unless infusion reactions occur or unless clinically indicated. Moreover, ECGs at EOI are not 
required unless infusion reactions occur. 
Table 8: 
Timing of Vital Signs and ECG Collections 
BDC-1001 or Pertuzumab dose only days 
Before infusion 
Maximum 2 hours 
End of infusion 
+ 5 minutes 
Combination dose days 
Before BDC-1001 infusion 
Maximum 2 hours 
End BDC-1001 infusion 
+ 5 minutes 
End of Pertuzumab infusion 
+ 5 minutes 
Before infusion, assessment of blood pressure and pulse rate will be preceded by at least 5 minutes of rest for the 
participant in a quiet setting without distractions (eg, television, mobile phone).  Vital signs and ECGs are not 
required after Cycle 2 for EOI unless infusion reactions occur or unless clinically indicated. 
6.9. 
Electrocardiograms 
Standard supine or semi-recumbent 12-lead ECGs will be performed at the time points outlined 
in the Schedule of Assessments.  All ECG measurements should be performed from a 
supine/semi-recumbent position.  Standard ECG parameters will be measured, including RR, PR, 
QRS, QT, and QTcF (to be specified in the eCRF).  All ECG measurements must be evaluated 
by the Investigator or delegated physician for the presence of abnormalities and clinical 
significance. ECGs are not required after Cycle 2 for EOI unless infusion reactions occur or 
unless clinically indicated.   
The timing of pre- and post-infusion ECG collections is presented in Table 8. 
6.10. Echocardiograms or Multi-gated Acquisition Scans 
Standard ECHOs or MUGAs will be performed. These assessments will be performed at 
screening, 6 weeks after the first study treatment, then every 3 months thereafter during 
treatment if no abnormal findings are noted.  In the presence of symptoms, monitoring should 
begin immediately (Schedule of Assessments).  Left ventricular ejection fraction will be 
measured by either ECHO or MUGA.  All ECHOs or MUGAs must be evaluated by the 
Investigator or delegated physician for the presence of abnormalities and clinical significance. 
6.11. Pulse Oximetry 
Pulse oximetry is a general method for measuring subject oxygenation in the clinic.  Peripheral 
capillary oxygen saturation will be monitored by pulse oximetry at the time points outlined in the 
Schedule of Assessments.  By detecting signs of early hypoxemia, pulse oximetry may lead to a 
more rapid treatment of serious hypoxemia (from possible pneumonitis, for example) and 
prevention of serious complications. 
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6.12. Prior and Concomitant Medications 
The Investigator or qualified designee will record medication, if any, taken by the subject during 
the trial.  Concomitant medications will be recorded at the time points outlined in the Schedule 
of Assessments.  Refer to Section 5.4 for detailed information regarding allowed and prohibited 
concomitant medications. 
6.13. Adverse Events 
AEs will be managed as described in Section 7 and in accordance with Schedule of Assessments.  
Investigators will assess the severity of AEs according to National Cancer Institute Common 
Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0), unless otherwise 
specified. 
6.14. Viral Screening  
6.14.1. 
Hepatitis B Screening 
Subjects with active HBV infection are defined as having a positive HBsAg.  A subject whose 
HBsAg is negative and HBcAb is positive may be enrolled if an HBV DNA test is negative and 
either the subject is treated with potent antiviral therapy or is retested for HBsAg and HBV DNA 
every month.  The test will be performed by local laboratory. 
6.14.2. 
Hepatitis C Screening 
Subjects with active HCV infection are defined as having a positive HCV antibody test followed 
by a positive HCV RNA test at Screening.  The HCV RNA test will be performed only for 
subjects who have a positive HCV antibody test.  Subjects who are positive for HCV antibody 
are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.  The test will be 
performed by local laboratory. 
6.14.3. 
HIV Screening 
Subjects with active HIV infection are defined as those as having a positive HIV antibody test.  
The test will be performed by local laboratory. 
6.15. Pregnancy Testing  
6.15.1. 
Pregnancy Testing  
Pregnancy is an exclusion criterion and women of childbearing potential must not be considering 
pregnancy during the study and for at least 7 months following the last dose of BDC-1001 or 
pertuzumab administered during the study.  Pregnancy tests should be performed for any woman 
of childbearing potential.  Pregnancy tests are not required for postmenopausal subjects 
(12 months since last menstruation) or subjects who have no possibility of pregnancy due to 
sterilization surgery, etc.  Serum ß-human chorionic gonadotropin (evaluated by local laboratory) 
will be evaluated at Screening.  Pregnancy testing will be performed at C1D1 before infusion, 
every 4 weeks during treatment, and at the EOT visit.  Positive urine pregnancy test will be 
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confirmed with a serum pregnancy test.  Testing may be determined 48 hours before 
administration of study treatment. 
In the Maintenance Phase, subjects are to be followed as described in Table 2. 
6.15.2. 
Pregnancy On-Study 
In the event of suspected pregnancy, a confirmatory serum pregnancy test should be performed.  
Subjects who become pregnant during the study must discontinue study treatment. 
The Investigator or designee must report any pregnancy that occurs during the study within 
24 hours of awareness using the same procedure as described for reporting SAEs (Section 7.2.4).  
The subject will be asked to provide information on the outcome of the pregnancy, including 
premature termination should the case arise.  Follow-up will be in accordance with regulatory 
guidance and at least 6 to 8 weeks after the estimated delivery date.  
6.16. Clinical Laboratory Safety Assessments 
Clinical laboratory tests will be conducted in accordance with the Schedule of Assessments.  
Laboratory values will be assigned toxicity grades, when available, using the NCI CTCAE v5.0 
scale.  Laboratory tests may be determined up to 48 hours before each dose during treatment.  
Comparable analytes may be collected according to local standards (eg. blood urea nitrogen 
[BUN] vs. urea, etc.) following notification of the Sponsor. 
The Investigator must review laboratory reports before treatment, document this review, and 
record any clinically significant changes occurring during the study as an AE (see Section 7.1).  
All laboratory reports must be filed in the source documents.  
In the Maintenance Phase, safety assessments will be performed per local standard of care.  See 
Table 2 for schedule and procedures.  
6.16.1. 
Chemistry 
Chemistry tests will be performed by a local laboratory and will include the following: 
• 
BUN, uric acid, total bilirubin, AST, ALT, alkaline phosphatase, lactate 
dehydrogenase, bicarbonate (total CO2), sodium, potassium, chloride, magnesium, 
calcium, phosphate, creatinine, amylase, total protein, and albumin. 
6.16.2. 
Hematology 
Hematology tests will be performed by a local laboratory and will include the following at all 
timepoints: 
• 
Red blood cell count, hemoglobin, hematocrit, and indices per local standards 
(eg, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and 
red blood cell distribution width).  
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• 
White blood cell count with differential (eg, absolute and percent neutrophils, 
lymphocytes, monocytes, eosinophils, basophils).  
• 
Platelet count. 
6.16.3. 
Coagulation 
Coagulation laboratory tests will be performed by local laboratory. 
Coagulation laboratory tests include: PT (or INR) and aPTT reported according to local 
standards.   
6.16.4. 
Urinalysis 
Urinalysis or urine dipstick should be conducted as outlined in the Schedule of Assessments.  
Urine tests will be performed by local laboratory include tests for pH, specific gravity, glucose, 
ketones, protein, leukocytes, nitrite, and bilirubin.   
6.17. Thyroid Function Testing 
TSH and free T4 will be conducted in accordance with the Schedule of Assessments.  TSH and 
free T4 may be determined up to -48 hours before the dose.  The tests will be performed by local 
laboratory. 
6.18. Serum Tumor Markers 
Serum tumor markers (eg, cancer antigen [CA27.29 and CA15-3, etc.]), will be tested by local 
laboratory per standard of care according to the Schedule of Assessments. 
Tumor markers may be used for exploratory determination of anti-tumor activity.  
6.19. Pharmacokinetics 
Serum will be collected from all subjects enrolled in the study for assessment of BDC-1001 PK.  
PK sampling should be conducted in accordance with the Schedule of Assessments.   
The actual time of study treatment administration and the exact time of blood sampling must be 
recorded in source document. 
Refer to the current version of the Laboratory Manual for detailed information. 
6.20. Immunogenicity (Anti-BDC-1001 Antibodies) 
Serum will be collected from all subjects enrolled in the study for assessment of anti-BDC-1001 
antibodies (ADAs).  ADA sampling will be conducted in accordance with the Schedule of 
Assessments.   
Refer to the current version of the Laboratory Manual for detailed information. 
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6.21. Exploratory Biomarker Assessments  
Exploratory biomarker analysis will be performed as part of this study to allow exploration of the 
mode of action, pharmacodynamic biomarker characterization of BDC-1001, and to potentially 
identify subjects most likely to benefit from treatment with BDC-1001 in the future. 
Blood will be collected for biomarker evaluation (including, but not limited to, immune cell 
activation, changes in blood based-biomarkers, and other biomarkers that are related to 
BDC-1001 mechanism of action and tumor immune biology) according to the Schedule of 
Assessments.  Samples will be processed to obtain their derivatives and may be evaluated for 
immune-related, tumor type-related, and other exploratory biomarkers.   
Any remaining samples collected for PK, biomarker assays, and immunogenicity assessment 
may be used for exploratory biomarker profiling, identification, and pharmacodynamic assay 
development purposes as appropriate if subject consents to future research. 
Refer to the current version of the Laboratory Manual for detailed information. 
6.22. Tumor Specimens 
6.22.1. 
Fresh Tissue Biopsy  
Screening fresh tumor tissue biopsy is required for all subjects.  
An on-treatment biopsy may be collected if safely accessible and clinically feasible, at the 
discretion of the Investigator.  An optional additional biopsy may be collected preferably at time 
of progression, response or at any time during the study. 
For freshly collected biopsy specimens, acceptable samples include those outlined below, 
provided there are tissue architecture regardless of needle gauge or retrieval method: 
• 
Core needle biopsy sample collection for deep tumor tissue; at least 3 cores  
• 
Excisional, incisional, punch, or forceps biopsy sample collection for cutaneous, 
subcutaneous, or mucosal lesions 
• 
Tumor tissue resections 
The following specimens are not acceptable: fine-needle aspiration (defined as samples that do 
not preserve tissue architecture and yield cell suspension and/or cell smears), brushing, cell 
pellets from pleural effusion, and lavage samples as well as tumor tissue that have been 
decalcified. 
Any remaining tumor samples may be used for future research including exploratory biomarker 
profiling, identification, and pharmacodynamic assay development purposes as appropriate if 
subject consents to future research. 
Refer to the current version of the Laboratory Manual for detailed information. 
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6.22.2. 
Archival Tissue 
Archival tumor tissue sample will be submitted if a fresh biopsy is not collected at Screening.  
Representative tumor specimens in paraffin blocks are preferred.  If an archival block is 
unavailable, unstained serial sections on slides must be submitted. 
The following specimen types are acceptable: resections, core needle biopsies, excisional, 
incisional, punch, or forceps biopsies.  For core needle biopsy specimens, preferably, at least 
3 cores embedded in a single paraffin block should be submitted for evaluation.  Fine-needle 
aspiration (defined as samples that do not preserve tissue architecture and yield cell suspension 
and/or cell smears), brushing, cell pellet from pleural effusion, and lavage samples are not 
acceptable.  Tumor tissue that has been decalcified is not acceptable. 
The submitted tumor tissue should be of good quality based on total and viable tumor content.  
An archival tumor specimen should be submitted if available.   
6.23. Tumor Assessments 
Tumor response will be assessed in accordance with the Schedule of Assessments.  All subjects 
will be evaluated for response of tumor lesions (CR, PR, SD, PD) by RECIST v1.1 criteria 
(Eisenhauer et al. 2009).  Subjects with a response of PD will also be evaluated by  Immunotherapy 
Response Evaluation Criteria in Solid Tumors (iRECIST) criteria (Seymour et al. 2017), and both 
results will be entered in the eCRF.  The iRECIST criteria are required to confirm PD. 
Subjects who experience an objective response (ie, CR or PR) should have a confirmatory 
assessment performed at least 4 weeks (+ 7 days) after the initial response.  
Subjects who have radiographic progression and have continued on study per iRECIST should 
have scans performed 4 to 6 weeks following immune unconfirmed progressive disease (iUPD) to 
immune confirmed progressive disease (iCPD).  The date of disease progression will be defined 
according to Appendix E (see Section 8.4.7, as well). 
Tumor imaging modality will be CT or magnetic resonance imaging (MRI).  The same imaging 
modality should be used for tumor assessments at Screening and those that will be performed every 
6 weeks (± 7 days) during the first 24 weeks after C1D1 and after that every 12 weeks (± 7 days) 
regardless of any delays in dosing.  The assessment will be conducted before Day 1 of each cycle 
if possible.  CT or MRI scans of the chest, abdomen and pelvis are mandatory.  However, if there 
is no brain metastasis at the time of Screening, brain CT or MRI should only be done when 
symptoms associated with brain metastasis occur.  If there are central nervous system metastases 
(eg, spinal cord, brain) and a CT or MRI is performed at Screening, then these lesions must be 
evaluated according to the schedule of assessment. 
CT and MRI scans will be performed using institutional standard operating procedures (SOPs).  
The same scan modality and machine should be used throughout the study for each subject, if 
possible.  Scans will be read by institutional radiologists and reported.  The reports will be filed in 
source documents and the results entered into the eCRF. 
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Tumor measurement will be conducted while the subject remains on study until progression of 
disease, withdrawal of consent, death, or loss to follow-up. 
Tumor assessment images will be collected and may be reviewed at the Sponsor’s discretion. 
During the Maintenance Phase, tumor assessments will be performed per local standard of care 
and will not be captured in the study database or submitted for central review. 
6.24. Survival Information 
The survival status of each subject will be monitored during study treatment and after 
discontinuation of study treatment for any reason (not applicable for subjects who have 
withdrawn from the study).  
During the study, the Medical Monitor may request that a survival report be conducted to obtain 
an accurate number of deaths across the study.  The Medical Monitor will provide instructions on 
these survival reports immediately before they commence as well as a timeline for contacting 
subjects.  
The cause of death will be recorded for subjects who die, if available. 
6.25. Procedures at End of Treatment and Follow-Up 
6.25.1. 
End of Treatment 
The date of EOT is defined as the date of the last dose of study drug administration.   
The EOT assessments, outlined in Schedule of Assessments, will be performed 14 days 
(± 7 days) after the last day of study drug administration.  If the required assessments at EOT 
have been performed during the treatment period, they do not need to be replicated. 
The same imaging tumor modality used at the time of Screening by CT or MRI scans should be 
performed.  CT or MRI scans of the chest, abdomen, and pelvis are mandatory.  However, if 
there is no brain metastasis at the time of Screening, brain CT or MRI should only be done when 
symptoms associated with brain metastasis occur (Section 6.23).  
The reason for treatment discontinuation should be recorded. 
For women deemed of childbearing potential, a pregnancy test should be conducted 
(Section 6.15.1).  
6.25.2. 
Safety Follow-Up 
The SFU visit assessments, outlined in the Schedule of Assessments, should occur 28 days 
(+7 days) after the last study treatment.  If the subject begins another anticancer therapy before 
the end of the 28 days (-7 days), every effort will be made to complete all the SFU assessments 
prior to beginning the new therapy.  In case of unresolved AEs, the Investigator will follow the 
AEs until the event has resolved or the condition has stabilized.  Every attempt will be made to 
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follow AEs through resolution. If assessments at EOT or treatment period are performed within 
this period, they can be considered to be the SFU data and there is no need to repeat them. 
6.25.3. 
Long-Term Follow-Up / End of Study 
All subjects who discontinue study treatment will be followed for:  
• 
Assessment of treatment-related AEs/SAEs until their resolution to baseline or 
Grade ≤ 1 
• 
Survival via a clinic visit or telephone call until any of the following: death, 
withdrawal of consent, lost to follow-up, the Sponsor notifies sites that survival 
follow-up is no longer required, or termination of the trial by the Sponsor 
Subjects discontinuing treatment for reasons other than radiographic progression will continue to 
have tumor assessments using the same modality that was used during study treatment.  These 
should occur every 12 weeks (± 14 days) for up to 2 years after the EOT, until any of the 
following occur: the subject has radiographic progression, the subject starts a new therapy for 
their cancer, the subject is lost to follow-up, the subject dies, the subject withdraws consent, the 
Sponsor notifies sites that tumor assessment is no longer required during LTFU, or the trial is 
terminated by the Sponsor.  Completion of LTFU (up to 2 years) is not required for a subject to 
be considered as having completed the clinical study. 
6.25.4. 
Treatment after the End of Study 
Upon completion of the study, the Sponsor will follow local regulatory/International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines 
for any follow-up treatment provided to subjects.  Each Investigator is responsible for ensuring 
that appropriate post-study care is provided for each subject’s medical condition. 
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7. 
ADVERSE EVENTS 
Adverse events should be collected/recorded in accordance with the Schedule of Assessments. 
AEs and SAEs will be collected from first dose of study drug to the end of the SFU period.  
SAEs that occur during screening will be collected only if the event is related to a study 
mandated procedure from Screening to the first dose of study drug. 
7.1. 
Adverse Event Definitions  
7.1.1. 
Adverse Event 
An AE is any unfavorable and unintended medical occurrence (including an abnormal laboratory 
finding) temporally associated with the use of an investigational product or protocol-imposed 
intervention whether or not considered related to the investigational product. 
The following are AEs: 
• 
Abnormal medical occurrence (eg, symptom, sign, laboratory test result, ECG, 
radiological scan, etc.) that emerges during the protocol-specified AE reporting 
period and is considered clinically significant by the Investigator 
• 
Worsening of a chronic or pre-existing medical condition in frequency or severity that 
is considered clinically significant by the Investigator 
• 
Complications that occur as a result of protocol-mandated interventions (eg, invasive 
procedures such as biopsies) 
The following are NOT AEs: 
• 
Signs/symptoms, laboratory abnormalities related to the natural disease course (ie, 
disease progression). Signs/symptoms of clinical sequelae resulting from disease 
progression will be reported as AEs/SAEs if they fulfill the AE/SAE definition.  
• 
Hospitalization or death due to disease progression 
• 
Planned or elective admissions to a hospital  
7.1.2. 
Serious Adverse Event 
An SAE is any AE that at any dose: 
• 
Results in death, 
• 
Is life-threatening, 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization, 
• 
Results in persistent or significant disability/incapacity, 
• 
Is a congenital anomaly/birth defect, or, 
• 
Is an important medical event. 
Note: The term “life-threatening” in the definition of “serious” refers to an event in which the 
subject was at risk of death at the time of the event; it does not refer to an event which 
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hypothetically might have caused death if it were more severe (ICH E2A Guideline. Clinical 
Safety Data Management: Definitions and Standards for Expedited Reporting, Oct 1994). 
7.2. 
Detecting and Reporting Adverse Events and Serious Adverse Events  
AE information that should be reported to the Sponsor includes, but is not limited to, the 
following: 
• 
Change in the event’s outcome, including recovery 
• 
New signs or symptoms or a change in the diagnosis 
• 
Change in causality based on new information 
• 
Significant new diagnostic test results 
• 
Additional narrative information on the clinical course of the event 
Adverse events (including AEs, SAEs) will be elicited by asking the subject a non-leading 
question.  A consistent methodology of non-directive questioning for eliciting AEs at all subject 
evaluation time points should be adopted. 
All AEs occurring after the first dose of study drug and up to the SFU visit will be recorded on 
the AE eCRF.  Medical conditions (including laboratory values/vital signs that are out of range) 
that were diagnosed or known to exist prior to the first dose of study drug will be recorded as 
part of medical history.  
At each visit, the Investigator should determine whether any AEs have occurred by evaluating 
the subject.  AEs may be directly observed, reported spontaneously by the subject, or elicited by 
questioning the subject.  Subjects should be questioned in a general way, without asking about 
the occurrence of any particular symptoms.  The Investigator must assess all AEs to determine 
seriousness, severity, and causality, in accordance with the definitions in Section 7.1.  The 
Investigator’s assessment must be clearly documented in the site’s source documentation with 
the Investigator’s signature.  All laboratory values must be evaluated by the Investigator as to 
clinical significance, consistent with institutional policies.  All abnormal laboratory values 
considered clinically significant by the Investigator and without a corresponding diagnosis must 
be recorded as an AE on the eCRF.  Abnormal laboratory findings attributed to the underlying 
disease are not considered clinically significant unless judged by the Investigator to be more 
severe or frequent than expected for the subject’s condition. 
Always report diagnosis as the AE or SAE term.  When a diagnosis is unavailable, report the 
primary sign or symptom as the AE or SAE term with additional details included in the narrative 
until a diagnosis becomes available.  
If the signs and symptoms are distinct and do not lead to a common diagnosis, they should be 
reported as individual entries of AE or SAE.  For serious events due to hospitalization, the reason 
for hospitalization must be reported as the SAE.  A pre-planned procedure or treatment requiring 
hospitalization for preexisting conditions which does not worsen in severity should not be 
reported as SAEs (refer to Section 7.1 for definitions).   
Any other serious, untoward event that occurs subsequent to the reporting period that the 
Investigator assesses as related to either study drug should be reported and managed as an SAE.  
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Investigator should follow subjects with AEs until the target event has resolved, to baseline or 
the condition has stabilized.  In case of unresolved AEs including significant abnormal 
laboratory values at the end of study assessment, these events will be followed up until resolution 
or until they are no longer clinically relevant. 
24-hour medical and safety coverage is available at 
 in United States, at 
 
 in France, at 
 in Italy, and at 
 in Spain. 
Maintenance Phase:  
To continue to collect important safety information on subject(s) in the Maintenance Phase, 
reporting of SAEs and other reportable events (pregnancy and overdose) will continue per 
protocol (see Table 2).  
Further, the following AEs, whether serious or not, will be reported using the same process as for 
reporting SAEs as described in Section 7.2.4 (though SAE reporting timeline requirements do 
not apply to non-serious events reported in these categories):  
• Adverse events, whether serious or not, leading to study treatment discontinuation  
• Adverse events, whether serious or not, leading to study treatment to be interrupted or 
delayed.  
Other non-serious AEs will not be collected by the Sponsor as they are unlikely to meaningfully 
change the safety profile established in the earlier phases of this study. 
7.2.1. 
Grading and Intensity 
All AEs will be graded according to the NCI CTCAE v5.0 and general guidelines outlined in 
Table 9. 
Table 9: 
NCI CTCAE v5.0 Definitions of Severity for Adverse Reactions 
Toxicity 
Grade / Details 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; no interventions 
required  
(an AE that is easily tolerated by the subject, causes minimal discomfort, and does not interfere with 
everyday activities) 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; some limitation of activities  
(an AE that is sufficiently discomforting to interfere with normal everyday activities; intervention 
may be needed) 
Grade 3 
Severe or medically significant but not immediately life-threatening; hospitalization or prolongation 
of hospitalization required; disabling; limitation of subject's ability to care for him/herself 
(an AE that prevents normal everyday activities; treatment or other intervention usually needed) 
Grade 4 
Life-threatening consequences; urgent intervention required  
(an event that puts the subject at immediate or potential risk of death, requires hospitalization, or 
which drastically impacts a subject’s well-being) 
Grade 5 
Death related to adverse event (fatal) 
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7.2.2. 
Relationship to Study Treatment / Causality 
The Investigator should assess causal relationship between an AE and the study treatment on the 
basis of his/her clinical judgment and the following definitions.  The causality assessment should 
be made based on the available information and can be updated as new information becomes 
available. 
Related: 
The AE follows a reasonable temporal sequence from study treatment administration and cannot 
be reasonably explained by the subject’s clinical state or other factors (eg, disease under study, 
concurrent diseases, and concomitant medications). 
• 
The AE follows a reasonable temporal sequence from study treatment administration 
and is a known reaction to the drug under study or its chemical group, or is predicted 
by known pharmacology. 
Not Related: 
• 
The AE does not follow a reasonable temporal sequence from study drug 
administration or can be reasonably explained by the subject’s clinical state or other 
factors (eg, disease under study, concurrent diseases, and concomitant medications). 
7.2.3. 
Outcome and Action Taken 
The outcome or action taken with respect to study treatment will be recorded on the eCRFs. 
7.2.4. 
Serious Adverse Event Reporting Requirements 
SAEs must be reported to the Sponsor within 24 hours of knowledge by the Investigator or staff. 
During the Maintenance Phase, SAE reporting will be done via the paper Safety Report Form. 
No data will be entered in the eCRF. The study clinical database will be closed after the last 
subject remaining on treatment enters the Maintenance Phase. 
7.3. 
Follow-up of Adverse Events and Serious Adverse Events 
• 
The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
Sponsor or designee to elucidate the nature and/or causality of the AE or SAE as fully 
as possible.  This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care professionals 
• 
If a subject dies during participation in the study or during a recognized follow-up 
period, the Investigator will provide the Sponsor or designee with a copy of any 
postmortem findings including histopathology if available 
• 
New or updated information will be recorded in the originally completed eCRF. For 
the Maintenance Phase, the information will be recorded using the paper Safety 
Report Form. 
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• 
The Investigator will submit any updated SAE data to the Sponsor or designee within 
24 hours of receipt of the information  
• 
All SAEs and non-serious Grade 3 or higher AEs must be followed until the event has 
resolved to the baseline or Grade 1, stabilized, or until the Investigator assesses it as 
non-resolvable/persisting or until last contact with the subject.  Other AEs still 
ongoing after discontinuation of the study treatment should be followed at least until 
last scheduled SFU visit, 28 days (+ 7 days) after the last dose of study drug 
administration. 
7.4. 
Pregnancy Reporting 
Pregnancies must be reported to the Sponsor within 24 hours of knowledge by the Investigator or 
staff.  For the Maintenance Phase, pregnancy reporting will be done via paper Pregnancy Report 
Form. 
7.5. 
Overdose Reporting 
An overdose in this study is defined as any of the following: 
• 
Any single dose of BDC-1001 that is ≥ 10% more than the assigned dose 
• 
An infusion duration that is < 45 minutes (not including flushing) 
For an overdose, the Investigator should contact the Medical Monitor immediately and document 
the quantity of the excess dose as well as the duration of the overdose in the eCRF.  Decisions 
regarding any treatments, dose interruptions or dose modifications should be made by the 
Investigator, in consultation with the Medical Monitor.   
For the Maintenance Phase, the Investigator should contact the Medical Monitor immediately in 
the event of an overdose and document the quantity of the excess dose as well as the duration of 
the overdose in a Safety Report Form. 
Overdose will not be reported as an AE/SAE although resulting symptoms should be reported. 
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8. 
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN 
A full Statistical Analysis Plan (SAP) will provide specific details on the analytical methods and 
data displays. 
8.1. 
Endpoints 
Study endpoints are outlined in Table 3. 
8.2. 
Determination of Sample Size 
Approximately 66 evaluable subjects will be randomized 1:1 to either the BDC-1001 
monotherapy arm or the BDC-1001 plus pertuzumab arm.  Within each arm, a Simon 2-stage 
design will be used to evaluate ORR.  It is assumed under the null hypothesis, that ORR will be 
≤ 20% (not considered clinically compelling) for both arms.  Based on the probability of 
accepting the poor drug (one-sided alpha level) at 5%, 80% power, P0 and P1 at 20% and 40% 
respectively, 18 subjects will be enrolled into the first stage.  If at least 5 objective responses are 
observed in an arm, the study will continue to enroll a total of 33 evaluable subjects to that arm.  
The null hypothesis will be rejected if at least 11 objective responses are observed out of the 
33 subjects in an arm. 
8.3. 
Analysis Populations 
8.3.1. 
Safety Analysis Set 
The Safety Analysis Set is defined as enrolled subjects who receive at least 1 dose of BDC-1001 
with or without pertuzumab.  The Safety Analysis Set will be used primarily for the analysis of 
safety, PFS, and OS data.  
8.3.2. 
Full Analysis Set (FAS) 
The Full Analysis Set (FAS) will be used primarily for the analysis of anti-tumor activity-related 
data.  The FAS will include subjects who meet the following criteria: 
• 
Receive at least 1 dose of BDC-1001 with or without pertuzumab 
• 
Have 1 or more measurable lesion(s) at baseline as assessed and at least 
1 postbaseline evaluable scan using RECIST v1.1 criteria at least 4 weeks after 
C1D1. 
8.3.3. 
Pharmacokinetic Analysis Set (PKAS) 
The Pharmacokinetic Analysis Set (PKAS) will include subjects who meet the following criteria: 
• 
Receive any dose of BDC-1001 with or without pertuzumab 
• 
Have 1 or more post-infusion PK datapoint 
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8.3.4. 
Pharmacodynamic Analysis Set (PDAS) 
The Pharmacodynamic Analysis Set (PDAS) will include subjects who meet the following 
criteria: 
• 
Receive any dose of BDC-1001 with or without pertuzumab 
• 
Have 1 or more set of biomarker data  
8.4. 
Statistical Methods 
8.4.1. 
Demographics and Baseline Characteristics 
Descriptive summaries of demographic and baseline characteristics will be tabulated for both 
Safety Analysis Set and FAS.  Subjects will be tabulated by study arm. 
8.4.2. 
Prior and Concomitant Medications 
Concomitant medications will be coded by the World Health Organization (WHO) Drug 
Dictionary to Anatomical Therapeutic Classification (ATC) and preferred drug name.  Prior and 
concomitant medications will be summarized by ATC level and preferred drug name and listed. 
8.4.3. 
Study Drug Exposure 
Descriptive statistics will be used to summarize study drug exposure including duration of 
treatment, cumulative dose of study drug, and number and percent of subjects with dose 
modifications (ie, dose interruption and permanent dose discontinuations). 
8.4.4. 
General Principles 
All individual subject data may be presented in the subject data listings. 
Continuous data will be summarized using the following summary statistics: the number of 
observations (N), mean, standard deviation, median, minimum, and maximum.  Categorical data 
will be summarized using counts and percentages.  All summaries will be presented by study arm 
and overall, when appropriate. 
8.4.5. 
Safety Analyses 
Safety will be assessed through summaries of AEs, SAEs, changes in laboratory test results, 
changes in vital signs and ECGs, and exposure to BDC-1001 and pertuzumab.  All safety 
analyses will be conducted in the Safety Analysis Set. 
Treatment-emergent AEs are defined as AEs that start on or after the first administration of study 
treatment.  The reported AE term will be assigned a standardized preferred term using Medical 
Dictionary for Regulatory Activities (MedDRA). 
TEAEs will be summarized based on the number and percentage of subjects experiencing the 
event by MedDRA system organ class and preferred term.  The causal relationship between the 
occurrence of an AE and study treatment will be judged by the Investigator.  In the event that a 
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subject experiences repeated episodes of the same AE, the event with the greatest severity grade 
and strongest causal relationship to study treatment will be used for purposes of incidence 
tabulations. 
AEs-summaries include: 
• 
All TEAEs 
• 
TEAEs by relationship (yes, no) to study treatment and maximum severity grade 
(according to NCI CTCAE v5.0) 
• 
TEAE by severity that are defined by NCI CTCAE v5.0 
• 
TEAEs with action of study treatment interrupted  
• 
TEAEs with action of study treatment discontinued 
• 
SAEs by relationship (yes, no) to study treatment 
• 
Immune-related AE 
Hematology and serum chemistries will be summarized in a descriptive manner. 
Laboratory values will be assigned toxicity grades, when available, using the NCI CTCAE v5.0 
scale.  Directional shifts in laboratory toxicity grades (comparing baseline grade with worst 
post-baseline grade) will be analyzed using standard shift tables, presenting number and 
proportion of subjects and their maximum grade shift.  For analytes without a toxicity grading 
scale, the shift table will present directional shifts from baseline to above or below the laboratory 
standard normal range using the maximum increase and/or decrease observed throughout the 
course of treatment/observation. 
8.4.5.1. 
Monitoring of Safety Data 
Continuous safety monitoring by an SRC will be adopted for each arm based on the rate of SAEs 
attributable to study treatment.  Continuous safety monitoring will be conducted to ensure ongoing 
evaluation of subject safety.   
A Bayesian toxicity monitoring rule will be implemented.  Specifically, if the probability (true 
study treatment related SAE rate > 30%) is > 70% in any given arm, the enrollment to that arm 
will be halted pending the SRC review.  A beta (0.5, 0.5) prior for the true study treatment-related 
SAE rate is utilized.  Table 10 shows the stopping boundaries for this safety monitoring rule in up 
to 33 subjects per treatment arm.  
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Table 10: 
Bayesian Toxicity Monitoring Safety Stopping Rules  
Number of Subjects 
Early Stop if Number of Subjects with Related SAE 
3-5 
≥ 2 
6-7 
≥ 3 
8-10 
≥ 4 
11-13 
≥ 5 
14-16 
≥ 6 
17-19 
≥ 7 
20-22 
≥ 8 
23-26 
≥ 9 
27-29 
≥ 10 
30-32 
≥ 11 
33 
≥ 12 
 
Reach Max N 
Abbreviations: N = number of subjects; SAE = serious adverse event 
An ad hoc meeting will be conducted to review accumulated safety data, including SAEs, if a 
threshold in Table 10 is crossed and the timing doesn’t fall in the regular SRC review meeting 
schedules (as set forth in the SRC Charter).  If the SRC considers the safety profile inadequate for 
BDC-1001 as monotherapy or in combination with pertuzumab, then enrollment to either or both 
arms may be stopped.  The SRC may also recommend stopping the entire study based on the safety 
review at any time. 
In addition to the stopping rules, if any subject dies due to an event attributable by the Investigator 
or Sponsor to BDC-1001 and/or pertuzumab, enrollment will be interrupted in all arms that include 
the implicated study treatment (ie, BDC-1001 or BDC-1001 + pertuzumab), pending review by 
the SRC. 
The SRC may recommend that enrollment and/or study treatment be interrupted for either or both 
arms should emerging safety data suggest an unacceptable risk. 
Although the decision of whether to close an arm will be made primarily based on the safety 
monitored continuously using Bayesian toxicity monitoring, the totality of data (including safety, 
efficacy, and PK, if available) will also be reviewed and considered in the final decision made by 
the Sponsor.  The decision will be communicated to sites in writing if the Sponsor determines one 
or both arms is to be closed. 
The SRC will not be providing oversight for the Maintenance Phase. 
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8.4.6. 
Pharmacokinetic and Pharmacodynamic Analyses 
Individual and mean serum BDC-1001 exposure (eg, Cmax and Cmin) will be tabulated and plotted 
by arm and compared to those in the Phase 1 study using a population PK analysis approach.  
Intersubject variability and drug accumulation will be evaluated.  
PK data from this study may also be used for separate pharmacokinetic/pharmacodynamic 
analyses; the results will be reported separately, if conducted. 
Exploratory pharmacodynamic analyses will include assessments of pharmacodynamic 
biomarkers in both tumor tissue and blood.  
The relationship between BDC-1001 concentration and selected efficacy and safety outcomes 
may be explored.  The correlation between biomarkers and clinical outcomes may be analyzed.   
PK and PD assessments will no longer be collected for subjects in the Maintenance Phase. 
8.4.7. 
Anti-Tumor Activity Analyses 
The anti-tumor activity endpoints of ORR, duration of response (DOR) and disease control rate 
will be analyzed and summarized for the subjects in FAS.  The endpoints of PFS and OS will 
also be analyzed and summarized for subjects in the Safety population.  Additional details will 
be provided in the SAP.   
The primary endpoint of ORR is defined as the proportion of subjects with best overall response 
of confirmed CR or PR as determined by the treating Investigator using RECIST v1.1 criteria 
(Appendix C RECIST v1.1 Criteria for Tumor Response).  Confirmed CR or PR will be defined 
as a repeat assessment performed no less than 4 weeks after the criteria for response is first met. 
The iRECIST criteria are required to confirm PD only and will not be performed at each tumor 
assessment. 
Duration of response (DOR) will be calculated for subjects who achieve confirmed CR or PR.  
For such subjects, DOR is defined as the duration from the start date of CR or PR (whichever 
response status is observed first) and subsequently confirmed, to the earliest of documented date 
of PD per RECIST v 1.1 or death.  
Disease control rate is defined as the best overall response rate of confirmed CR, PR, or stable 
disease lasting 24 or more weeks (≥ 2 tumor assessments) following the initiation of BDC-1001.   
Progression-free survival (PFS) is defined as the duration from the date of first study treatment 
administration (C1D1) to the earliest date of documented PD per RECIST v1.1 or death.  A death 
will be considered a PFS event.   
Overall survival (OS) is defined as the duration from the date of first study treatment 
administration to the date of death, irrespective of cause.  
Time-to-event endpoints of DOR, PFS, and OS will be summarized descriptively using the 
Kaplan-Meier method with 95% CIs calculated.  The right-censored criteria will be described in 
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SAP, and the progression or censoring date will be determined based on described conventions.  
Median duration of study follow-up will also be presented. 
Subjects will not be followed for OS in the Maintenance Phase. 
8.4.8. 
Biomarker Analysis 
Exploratory biomarker analyses may include assessments of pharmacodynamic biomarkers in 
both tumor tissue and blood, when appropriate for data collected.  Biomarkers that may correlate 
with anti-tumor activity or immunomodulatory effects of BDC-1001 will be explored, as 
appropriate.  
BDC-1001 biological activity will be assessed by exploring pharmacodynamic or predictive 
biomarkers that may correlate with activity or help to identify subjects likely to respond to 
BDC-1001 and/or BDC-1001 plus pertuzumab combination treatment, when appropriate for data 
collected.  The correlation between biomarkers and clinical outcomes may be analyzed. 
8.4.9. 
Immunogenicity Analysis 
Incidence, titer, and time-course of ADA response will be reported by arm.  The potential 
correlation of immunogenicity with PK, pharmacodynamic, and safety parameters may be 
assessed. 
The incidence of ADA formation in each dose group will be summarized by frequency counts 
and percentages.  The impact of positive results on PK, safety and biological activity will be 
assessed when appropriate for data collected.   
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9. 
STUDY ADMINISTRATION 
9.1. 
Ethical Conduct of Study 
This study will be conducted under applicable local legal and regulatory requirements, as well as 
the guiding principles of the World Medical Association Declaration of Helsinki, and will 
include current Good Clinical Practice (GCP) according to ICH guidelines.  
Specifically, this study is based on adequately performed laboratory and animal experimentation; 
the study will be conducted under a protocol reviewed and approved by an independent ethics 
committee (IEC); the study will be conducted by scientifically and medically qualified persons; 
the anticipated benefits of the study are in proportion to the risks; the rights and welfare of the 
subjects will be respected; the physicians conducting the study do not find the hazards to 
outweigh the potential benefits; and each subject will provide written informed consent before 
any protocol-specific tests or evaluations are performed. 
9.1.1. 
Approval by Independent Ethics Committee or Institutional Review Board 
Before initiating the study, the Investigator must obtain written confirmation from the 
IEC/institutional review board (IRB) that the IEC/IRB is properly constituted and compliant with 
all requirements and local regulations.  The Investigator will provide the IEC/IRB with all 
appropriate material, such as the protocol, current BDC-1001 and pertuzumab Investigator’s 
Brochures, site- or country-specific ICF, and other written information provided to the subjects.  
IEC/IRB approval of the protocol, informed consent document, and all recruiting materials are 
obtained in writing by the Investigator and copies are received by the Sponsor.  A copy of the 
IEC/IRB confirmation will be provided to the Sponsor.  IEC/IRB approval will be obtained for 
any substantial protocol amendments and informed consent revisions before implementing the 
changes.  The Investigator will provide appropriate reports on the progress of the study to the 
IEC/IRB and to the Sponsor or designee in accordance with applicable local regulations. 
9.1.2. 
Subject Informed Consent 
The subject’s written informed consent must be obtained prior to his/her participation in the 
study and should be documented in the subject’s medical records.  The ICF should be signed and 
personally dated by the subject and by the person who conducted the informed consent 
discussion, consistent with local institutional policies.  The original signed ICF should be 
retained in accordance with institutional policy, and a copy of the signed consent form should be 
provided to the subject.  The date that informed consent was given should be recorded on the 
eCRF. 
The ICF should provide an adequate explanation of the aims, methods, anticipated benefits, and 
potential hazards of the study and before any protocol-specific Screening procedures or any 
study treatments are administered.  The written ICF should be prepared in the local language(s) 
of the potential subject population, consistent with national and local regulations and GCP. 
In obtaining and documenting informed consent, the Investigator should comply with the 
applicable regulatory requirements, and should adhere to GCP and to the ethical principles that 
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have their origin in the Declaration of Helsinki.  The consent form and any revision(s) should be 
approved by the IRB prior to being provided to potential subjects. 
If the subject cannot read, then according to ICH GCP Guideline, Section 4.8.9, an impartial 
witness should be present during the entire informed consent discussion.  This witness should 
sign the ICF after the subject has orally consented to the subject’s participation and, if possible, 
signed the ICF.  By signing the ICF, the witness attests that the information in the ICF and any 
other written information was adequately explained to and apparently understood by the subject 
and that informed consent was freely given by the subject. 
Suggested model text for the ICF for the study and any applicable subparts (genomic, PK, etc.) is 
provided in the Sponsor ICF template for the Investigator to prepare the documents to be used at 
his or her site. 
For studies in the United States, an additional consent is required for the Health Insurance 
Portability and Accountability Act (HIPAA). 
The consent form should be signed and personally dated by the subject or legally acceptable 
representative prior to his/her participation in the study. 
9.1.3. 
Investigator Reporting Requirements  
In accordance with applicable regulatory requirements, the Investigator is obligated to inform the 
IRB/IEC of progress of the study and notify the IRB/IEC of study closure.  The Investigator 
must also provide the Sponsor with copies of IRB/IEC correspondence that relate to study 
approvals, updates, or changes.  The Investigator is also responsible for forwarding to the 
IRB/IEC reports of any SAEs from other studies conducted with the same investigational 
product that were provided by the Sponsor. 
9.1.4. 
Sponsor Safety Reporting to Regulatory Authorities / Investigator Sites 
The Sponsor or its representative is required to report certain study events in an expedited 
manner to the Food and Drug Administration, the European Medicines Agency’s EudraVigilance 
electronic system and all country Regulatory Authorities where the study is being conducted, 
according to local applicable regulations.  The sponsor or designee shall notify the Investigator 
sites of serious, related, and unexpected AE(s) per local country requirements. 
9.1.5. 
Serious Adverse Event Notification to the Institutional Review Board/ 
Independent Ethics Committee  
Suspected unexpected serious adverse reactions will be reported to the IRB/IEC according to 
their institutional policy by the Investigator or Sponsor (or Sponsor designee) according to 
country requirements.  Copies of each report and documentation of IRB/IEC notification and 
acknowledgement of receipt will be kept in the Investigator’s study file.  
9.1.6. 
Confidentiality 
All information concerning BDC-1001 or pertuzumab is considered confidential by the Sponsor. 
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Subject confidentiality will be maintained per local legal and regulatory requirements and ICH 
GCP guidelines.  To comply with GCP guidelines and requirements, subject records will be 
reviewed during monitoring visits and audits conducted by the Sponsor, Sponsor's 
representatives, or health authorities.  During these activities, every reasonable effort will be 
made to keep medical information, including subject identifying information, as confidential as 
possible as required by law. 
9.2. 
Regulatory: Data Quality Control and Quality Assurance 
All subject data relating to the study will be recorded in the eCRF unless defined differently with 
the site.  The Investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the eCRF. 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered into the eCRF. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of subjects are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study agreements, 
ICH GCP, and all applicable regulatory requirements. 
9.2.1. 
Compliance with Laws and Regulations 
This study will be conducted in accordance with the ICH E6 Guideline for GCP, and applicable 
local country laws and guidelines. 
9.2.2. 
Study Monitoring and Data Collection 
The Sponsor or contract research organization monitor are responsible for contacting and visiting 
the Investigator for the purpose of inspecting the facilities and, upon request, inspecting the 
various records of the study (eg, eCRFs, source data, and other appropriate documents). 
The monitor is responsible for visiting clinical site(s) at regular intervals throughout the study to 
verify adherence to the protocol, accuracy, completeness, consistency of data, and adherence to 
ICH GCP and local regulations on the conduct of clinical research.  In accordance with ICH 
GCP and the Sponsor’s audit plans, this study may be selected for audit by representatives from 
Sponsor.  Inspection of site facilities and review of study-related records will occur in order to 
evaluate the study conduct and compliance with the protocol, ICH GCP, and applicable 
regulatory requirements. 
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The monitor is responsible for inspecting eCRFs and ensuring completeness of the study 
essential documents.  The monitor should have access to subject medical records and other 
study-related records needed to verify the eCRFs. 
The monitor will communicate deviations from the protocol, SOPs, GCP, and applicable 
regulations to the Investigator and will ensure actions that are taken to prevent recurrence of the 
detected deviations are documented. 
The Investigator agrees to cooperate with the monitor to ensure that any issues detected during 
the course of these monitoring visits are addressed, documented, and resolved. 
The study clinical database will be closed after the last subject remaining on treatment enters the 
Maintenance Phase. All data collected prior to implementation of the Maintenance Phase will be 
reported in a clinical study report. Data from the safety database will be summarized or listed 
separately. 
9.2.3. 
Audit and Inspection 
The Sponsor or third-party designee (contract or consultant) Clinical Quality Assurance (CQA) 
auditors, which is independent of and separate monitoring or quality control functions, may audit 
clinical Investigator sites to evaluate trial conduct and compliance with the protocol, SOPs, GCP 
and applicable regulatory requirements. 
If regulatory authorities request an inspection, the Investigator must inform the Sponsor 
immediately that such request has been made. 
9.2.4. 
Protocol Adherence 
This protocol defines the study objectives, the study procedures, and the data to be collected on 
study participants.  Additional assessments required to ensure safety of subjects should be 
administered as deemed necessary on a case-by-case basis.  Under no circumstances is a site 
Investigator allowed to collect additional data or conduct any additional procedures for any 
research-related purpose involving any investigational drugs under the protocol.  Investigators 
ascertain that they will apply diligence to avoid protocol deviations.  If an Investigator feels a 
protocol deviation would improve the conduct of the study, this deviation must be considered as 
a protocol amendment.  Unless such an amendment is agreed upon by the Sponsor and approved 
by the IRB/IEC and health authorities, where required, it cannot be implemented. 
9.2.5. 
Protocol Deviations 
The Investigator should conduct the study in compliance with the protocol agreed to by Sponsor 
and, if required, by the regulatory authority(ies), and which was given favorable opinion by the 
IRB/IEC. 
If a subject was ineligible or received the incorrect dose or investigational treatment, and had at 
least 1 administration of study treatment, information should be collected for safety purposes. 
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A deviation to any protocol procedure or waiver to any stated criteria is not allowed in this study 
except where necessary due to potential hazard(s) to the subject.  The Sponsor must be notified 
of all intended or unintended deviations to the protocol (eg, inclusion/exclusion criteria, dosing, 
missed study visits) on an expedited basis. 
The Investigator, or person designated by the Investigator, should document and explain any 
deviation from the approved procedures in the protocol. 
The Investigator should notify the IRB/IEC of deviations from the protocol in accordance with 
local procedures. 
9.2.6. 
Records Retention 
The Investigator must retain records and documents, including signed ICF, pertaining to the 
conduct of this study.  ICH Guideline for GCP (refer to Section 4.9 of the guideline) and US 
FDA regulations (21 CRF 312.62) require that records and documents pertaining to the conduct 
of this study and the distribution of study treatment, including ICFs, laboratory test results, and 
medication inventory records, must be retained by the Principal Investigator for (i) 2 years after 
the last marketing application approval in an ICH region, (ii) after at least 2 years have elapsed 
since formal discontinuation of clinical development of BDC-1001, or (iii) for a longer period as 
required by national or local law (at least 25 years from study completion in the EU).  No records 
may be destroyed without the written approval of the Sponsor.  No records may be transferred to 
another location or party without written notification to the Sponsor. 
9.2.7. 
Investigator Reporting Policy 
A study site may not publish results of a study until after a coordinated multicenter publication 
has been submitted for publication.  Thereafter, the study site will have the opportunity to 
publish the results of the study, provided that the Sponsor has had the opportunity to review and 
comment on the study site’s proposed publication prior to its being submitted for publication 
with the prior advice of Sponsor’s Legal Affairs and with proper regard to the protection of 
subjects’ identities. 
9.3. 
Termination 
The Sponsor plans to terminate this study following completion of the study objectives.  
However, the Sponsor may terminate the study at any time by sending a written notice of the 
termination reasons to the Investigator.  If an Investigator or the Investigator’s IEC/IRB intends 
to terminate participation in the study, the Investigator must inform the Sponsor immediately and 
provide the rationale for such termination. 
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Litiere, J. Dancey, A. Chen, F. S. Hodi, P. Therasse, O. S. Hoekstra, L. K. Shankar, J. D. 
Wolchok, M. Ballinger, C. Caramella, E. G. de Vries, and Recist working group. 2017. 
'iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics', 
Lancet Oncol, 18: e143-e52. 
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Singh, M., H. Khong, Z. Dai, X. F. Huang, J. A. Wargo, Z. A. Cooper, J. P. Vasilakos, P. Hwu, 
and W. W. Overwijk. 2014. 'Effective innate and adaptive antimelanoma immunity 
through localized TLR7/8 activation', J Immunol, 193: 4722-31. 
Thompson J.A., B.J. Schneider, J. Brahmer, M.A. Zaid, A. Achufusi, P. Armand, M. K. 
Berkenstock, B. Bermas, T. Braaten, L.E. Budde, S. Chokshi, M. Davies, C. Deng, A. 
Awotiwon, L. Hang, Y, Gesthaler, M. Jain, P. Jain,  B.H. Kaffenberter, M. Khalil, M.G. 
Lechner, T. Li, A. Marr, S. McGettigan, J. McPherson, T. Medina, N.A. Mohindra, A.J. 
Olszanski, O. Oluwole, S. P. Patel, J. Prosek, S. Reddy, P. Reid, J. Ryan, M. Ryder, B. 
Santomasso, S. Shofer, J. A. Sosman, U. Wang, V. G. Zaha, S. Zucker. 2023. 
Management of Immunotherapy-Related Toxicities, Version1.2024, NCCN Clinical 
Practice Guidelines in Oncology. Accessed 13 March 2024. 
https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf. 
World Health Organization. 2021. 'Breast Cancer', Accessed March 20. 
https://www.who.int/news-room/fact-sheets/detail/breast-cancer. 
 
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11. 
APPENDICES 
Appendix A: Infusion Reaction Guideline 
 
From Rosello, Blasco et al., Management of infusion reactions to systemic anticancer therapy: ESMO Clinical 
Practice Guidelines, Ann Oncol, 2018 (Rosello et al. 2018) 
 
 
 
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Appendix B: Management of Cytokine Release Syndrome  
 
 
 
Source: (Lee et al. 2019) 
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From ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with 
Immune Effector Cells (Lee et al. 2019). 
 
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Appendix C: RECIST v1.1 Criteria for Tumor Response 
Table 11: 
RECIST v1.1 Criteria for Tumor Response 
Disease Response Criteria for Target and Non-target Lesions 
Evaluation of Target lesions 
Complete Response (CR): 
Disappearance of all target lesions.  Pathologic nodes must have a 
reduction in the short axis to < 10 mm. 
Partial Response (PR): 
At least a 30% decrease in the sum of the diameters of target lesions, 
taking as reference the baseline sum diameters. 
Stable Disease (SD): 
Neither sufficient shrinkage to qualify for PR nor sufficient increase 
to qualify for PD, taking as reference the smallest sum LD since the 
treatment started. 
Progressive Disease (PD): 
At least a 20% increase in the sum of the diameters of target lesions, 
taking as reference the smallest sum on study recorded since the 
treatment started or the appearance of 1 or more new lesions.  In 
addition to 20% increase, the sum must also demonstrate an absolute 
increase of at least 5 mm. 
Evaluation of Non-target Lesions 
Complete Response (CR): 
Disappearance of all non-target lesions and normalization of tumor 
marker level. 
Incomplete Response/ Stable Disease 
(SD): 
Persistence of 1 or more non-target lesion(s) or/and maintenance of 
tumor marker level above the normal limits. 
Progressive Disease (PD): 
Appearance of 1 or more new lesions and/or unequivocal 
progression of existing non-target lesions. 
Abbreviations: CR = complete response; LD = longest diameter PD = progressive disease; PR = partial response; 
SD = stable disease 
Source: (Eisenhauer et al. 2009). 
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Table 12: 
RECIST v1.1 Overall Response Criteria 
Subjects with Target and Non-target Lesions 
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR / Non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all 
evaluated 
No 
PR 
SD 
Non-PD or not all 
evaluated 
No 
SD 
Not evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
Subjects with Non-target Lesions Only 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR / Non-PD 
No 
Non-CR / Non-PD 
Not all evaluated 
No 
NE 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
Abbreviations: CR = complete response; NE = unevaluable; PD = progressive disease; PR = partial response; 
SD = stable disease 
Source: (Eisenhauer et al. 2009). 
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Table 13: 
Best Overall Response When Confirmation of CR and PR Required 
Overall Response 
First Time Point 
Overall Response 
Subsequent Time 
Point 
Best Overall Response 
CR 
CR 
CR 
CR 
PR 
Stable, PD, or PRa 
CR 
Stable 
Stable provided that minimum criteria for Stable duration met.  
Otherwise PD. 
CR 
PD 
Stable provided that minimum criteria for Stable duration met.  
Otherwise PD. 
CR 
NE 
Stable provided that minimum criteria for Stable duration met.  
Otherwise PD. 
PR 
CRb 
PR 
PR 
PR 
PR 
PR 
Stable 
Stable 
PR 
PD 
Stable provided that minimum criteria for Stable duration met.  
Otherwise PD. 
PR 
NE 
Stable provided that minimum criteria for Stable duration met.  
Otherwise PD. 
NE 
NE 
NE 
Abbreviations: CR = complete response; NE = non-evaluable; PD = progressive disease; PR = partial response 
a 
If a CR is truly met at a first time point, then any disease seen at a subsequent time point, even disease meeting 
PR criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR).  
Best response will depend on whether minimum duration of Stable Disease is met.  However, sometimes ‘CR’ 
may be claimed when subsequent scans suggest small lesions were likely still present and in fact the subject has 
PR, not CR, at the first time point.  Under these circumstances, the original CR will be changed to PR and the 
best response is PR. 
b 
Every effort will be made to confirm the CR.  For such cases where CR is not subsequently confirmed, then best 
overall response is PR.   
Source: (Eisenhauer et al. 2009) 
 
 
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Appendix D: iRECIST Criteria for Tumor Response 
Table 14: 
iRECIST Criteria for Tumor Response 
RESPONSE CATEGORY 
CRITERIA  
Complete Response (iCR) 
All lesions resolved 
Partial Response (iPR) 
At least a 30% decrease in the sum of the diameters of target lesions, 
taking as reference the baseline sum diameters. 
Progressive Disease (iPD) 
At least a 20% increase in the sum of the diameters of target lesions, 
taking as reference the smallest sum on study recorded since the 
treatment started or the appearance of 1 or more new lesions. In 
addition to 20% increase, the sum must also demonstrate an absolute 
increase of at least 5 mm 
Wait up to 12 weeks to confirm PD to account for flare 
Stable Disease (iSD) 
Does not meet other criteria 
Abbreviations: iCR = immune complete response; iPD = immune progressive disease iPR = immune partial 
response; iSD = immune stable disease  
Source: (Seymour et al. 2017) 
Table 15: 
iRECIST Guidelines for Progression Evaluation 
Any factor below on the confirmatory scan (after iUPD) indicates iCPD 
Target Lesions 
SoD increases ≥ 5 mm from iUPD TL 
SoD does not have to increase 20% from iUPD 
Non-Target Lesions 
Any further increase in size (qualitative assessment) from an iUPD 
NTL 
Does not have to meet “unequivocal” standard 
New Lesions 
There are ANY additional new lesions 
OR 
Size of previously detected new lesions increases 
Target NL: NL iSoD increases ≥ 5 mm 
NT NL: any significant growth 
Any factor below indicates progression (iUPD) after iSD/iPR/iCR 
Target Lesions 
SoD crosses PD threshold (1st time, or again) 
Based on the nadir (ie, smallest value ever) 
Non-Target Lesions 
New unequivocal progression 
OR 
If already showed PD, and did not regress, ANY growth 
New Lesions 
New lesions of ANY size appear for the first time, or additional new 
lesions appear 
If new lesions had previously appeared, and are still present, 
ANY growth 
Target NL: NL iSoD increases ≥ 5 mm 
NT NL: visible growth 
Note: track nadir for target NL iSoD and total # of new lesions 
Abbreviations: TL = target lesion; NL = new lesion; NT NL = non-target new lesion; iCPD = immune confirmed 
progressive disease; iUPD = immune unconfirmed progressive disease; SoD = sum of diameters for all target 
lesions; iSoD = immune sum of diameters for new lesion target  
Source: (Seymour et al. 2017) 
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Appendix E: Statistical Consideration for Defining Date of iRECIST PD 
• 
iUPD subsequently confirmed: The date used is the first UPD date. 
• 
iUPD never confirmed: 
▪  If a subsequent iSD, iPR or iCR is seen, the initial iUPD is ignored 
▪  Otherwise, iUPD date is used 
Abbreviations: iCR = immune confirmed response; iPR = immune partial response; iSD = immune stable disease; 
iUPD = immune unconfirmed progressive disease; UPD = unconfirmed progressive disease
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Appendix F: Summary of Changes from Version 2.0 to 3.0 
The protocol was revised to introduce a Maintenance Phase to allow any subject still receiving 
study drug to continue to receive BDC-1001.  Other administrative changes, clarification, and 
formatting changes were made throughout the protocol. 
 
Protocol Version 
Summary of Changes 
3.0 
Incorporate a Maintenance Phase to allow any subject(s) still receiving study treatment to 
continue on the study: 
• 
Synopsis, Table 2 (Overview of Schedule of Assessments – Maintenance Phase – 
Q2W Dosing), Sections 3.1, 3.1.3, 4.3, 6, 6.15.1, 6.16, 6.23, 7.2, 7.2.4, 7.3, 7.4, 
7.5,  8.4.5.1, 8.4.6, 8.4.7, and 9.2.2 
Update records retention requirements to comply with health authorities: 
• Section 9.2.6 
Other administrative changes, clarification, and formatting changes were made throughout 
the protocol. 
 
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Document Approvals
Approved Date: 01 Aug 2024
Approval Task
Verdict:  Approved
01-Aug-2024 15:37:49 GMT+0000
Approval Task
Verdict:  Approved
01-Aug-2024 16:31:25 GMT+0000
Number: CLIN-00059    Approved Date: 01 Aug 2024