A First-in-human Study Using BDC-1001 as a Single Agent and in Combination With Nivolumab in Advanced HER2-Expressing Solid Tumors

Study Overview
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Brief Summary
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A first-in-human study using BDC-1001 as a single agent and in combination with nivolumab in HER2 expressing advanced malignancies

Detailed Description
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This study has four parts. Part 1 is a dose escalation of BDC-1001 as a single agent to determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), or maximum protocol dose (MPD) recommended for Part 3. In Part 3, the selected dose will be administered as monotherapy to patients with selected advanced malignancies. Part 2 is a dose escalation of BDC-1001 in combination with nivolumab to determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), or maximum protocol dose (MPD) recommended for Part 4. In Part 4, the selected dose will be administered in combination with nivolumab to patients with selected advanced malignancies.

Official Title
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Phase 1/2 Study of BDC-1001 as a Single Agent and in Combination With Nivolumab in Patients With Advanced HER2-Expressing Solid Tumors

Conditions
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HER2-positive Solid Tumors, HER2-positive Breast Cancer, HER2-positive Colorectal Cancer, HER2-positive Gastroesophageal Cancer, HER2-positive Endometrial Cancer

Intervention / Treatment
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* Drug: BDC-1001
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patient must have an advanced solid tumor with documented HER2-protein expression or gene amplification for which approved therapies have been exhausted or are not clinically indicated. Measurable disease as determined by RECIST v.1.1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Tumor tissue (archival or collected prior to the study start) available for exploratory biomarker evaluation. Key Exclusion Criteria: History of severe hypersensitivity to any ingredient of the study drug(s), including trastuzumab or other monoclonal antibody. Previous treatment with a TLR 7, TLR 8 or a TLR 7/8 agonist. Impaired cardiac function or history of clinically significant cardiac disease Human Immunodeficiency virus (HIV) infection, active hepatitis B infection, or hepatitis C infection. Active SARS-CoV-2 infection Untreated central nervous system (CNS), epidural tumor or metastasis, or brain metastasis. Other protocol defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multiple ascending dose and dose-expansion of BDC-1001 administered as a single agent or in combination with nivolumab.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single agent BDC-1001<br>Escalating doses followed by expansion targeting HER2-expressing advanced malignancies | Drug: BDC-1001<br>* Immune stimulating antibody conjugate (ISAC), consisting of an anti-HER2 monoclonal antibody conjugated to a TLR 7/8 dual agonist<br>|
| Experimental: Combination BDC-1001 plus nivolumab<br>Escalating doses followed by expansion targeting HER2-expressing advanced malignancies | Drug: BDC-1001<br>* Immune stimulating antibody conjugate (ISAC), consisting of an anti-HER2 monoclonal antibody conjugated to a TLR 7/8 dual agonist<br>Drug: Nivolumab<br>* Programmed death receptor-1 (PD 1)-blocking antibody<br>* Other names: Opdivo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) and serious adverse events (SAEs) | Escalation period | 2 years | 
| Incidence and nature of dose-limiting toxicities (DLTs) | Escalation period | up to 21 days | 
| Incidence of potential-immune related toxicities | Escalation period | 2 years | 
| Maximum tolerable dose (MTD) or a tolerated dose below MTD | Escalation period | 2 years | 
| Objective response rate (ORR) of confirmed complete or partial responses (CR, PR) | Expansion period | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK (Cmax) of BDC-1001 | Escalation and expansion periods | 2 years | 
| PK (Cmin) of BDC-1001 | Escalation and expansion periods | 2 years | 
| PK (AUC0-t) of BDC-1001 | Escalation period | 2 years | 
| PK (AUC0-inf) of BDC-1001 | Escalation period | 2 years | 
| PK (CL) of BDC-1001 | Escalation period | 2 years | 
| PK (Vz) of BDC-1001 | Escalation period | 2 years | 
| PK (t1/2) of BDC-1001 | Escalation period | 2 years | 
| Objective response rate (ORR) using RECIST 1.1 | Escalation period | 2 years | 
| Duration of response (DOR) | Escalation and expansion periods | 2 years | 
| Disease control rate (DCR) of confirmed CR, PR, or stable disease (SD) lasting 4 or more weeks | Escalation and expansion periods | 2 years | 
| Progression Free Survival (PFS) | Escalation and expansion periods | 2 years | 
| Incidence of anti-BDC-1001 antibodies | Escalation and expansion periods | 2 years | 
| Incidence of adverse events (AEs) and serious adverse events (SAEs) | Expansion period | 2 years | 
| Incidence of potential-immune related toxicities | Expansion period | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2, ERBB2, Immunotherapy, Gastric Cancer, Gastroesophageal junction, Breast Cancer, Stomach Cancer, Colorectal Cancer, Gastrointestinal Cancer, Non-Small Cell Lung Cancer, Biliary Tract Cancer, Head and Neck Cancer, Urothelial Cancer, Endometrial Cancer, TLR7/8 agonist