HER2-positive Breast Cancer, HER2-positive Colorectal Cancer, HER2-positive Endometrial Cancer, HER2-positive Gastroesophageal Cancer, HER2-positive Solid Tumors
Conditions
Keywords
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
Brief summary
A first-in-human study using BDC-1001 as a single agent and in combination with nivolumab in HER2 expressing advanced malignancies
Detailed description
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. Bolt amended the protocol to transition any subjects still receiving BDC-1001 to continue receiving BDC-1001 in the Maintenance Phase. Subjects remaining on BDC-1001 will continue to receive BDC-1001 until a criterion for discontinuation has been met.
Interventions
DRUGBDC-1001
Immune stimulating antibody conjugate (ISAC), consisting of an anti-HER2 monoclonal antibody conjugated to a TLR 7/8 dual agonist
DRUGNivolumab
Programmed death receptor-1 (PD 1)-blocking antibody
Sponsors
Bristol-Myers Squibb
Bolt Biotherapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multiple ascending dose and dose-expansion of BDC-1001 administered as a single agent or in combination with nivolumab.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events (AEs) and serious adverse events (SAEs) | 2 years | Escalation period |
| Incidence and nature of dose-limiting toxicities (DLTs) | up to 21 days | Escalation period |
| Incidence of potential-immune related toxicities | 2 years | Escalation period |
| Maximum tolerable dose (MTD) or a tolerated dose below MTD | 2 years | Escalation period |
| Objective response rate (ORR) of confirmed complete or partial responses (CR, PR) | 2 years | Expansion period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK (Vz) of BDC-1001 | 2 years | Escalation period |
| PK (t1/2) of BDC-1001 | 2 years | Escalation period |
| Objective response rate (ORR) using RECIST 1.1 | 2 years | Escalation period |
| Duration of response (DOR) | 2 years | Escalation and expansion periods |
| PK (Cmax) of BDC-1001 | 2 years | Escalation and expansion periods |
| Progression Free Survival (PFS) | 2 years | Escalation and expansion periods |
| Incidence of anti-BDC-1001 antibodies | 2 years | Escalation and expansion periods |
| Incidence of adverse events (AEs) and serious adverse events (SAEs) | 2 years | Expansion period |
| Incidence of potential-immune related toxicities | 2 years | Expansion period |
| Disease control rate (DCR) of confirmed CR, PR, or stable disease (SD) lasting 4 or more weeks | 2 years | Escalation and expansion periods |
| PK (Cmin) of BDC-1001 | 2 years | Escalation and expansion periods |
| PK (AUC0-t) of BDC-1001 | 2 years | Escalation period |
| PK (AUC0-inf) of BDC-1001 | 2 years | Escalation period |
| PK (CL) of BDC-1001 | 2 years | Escalation period |
Countries
France, South Korea, Spain, United States
Outcome results
None listed