A First-in-human Study Using BDC-1001 As a Single Agent and in Combination with Nivolumab in Advanced HER2-Expressing Solid Tumors
- Conditions
- HER2-positive Colorectal CancerHER2-positive Solid TumorsHER2-positive Endometrial CancerHER2-positive Breast CancerHER2-positive Gastroesophageal Cancer
- Interventions
- Registration Number
- NCT04278144
- Lead Sponsor
- Bolt Biotherapeutics, Inc.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 175
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Single agent BDC-1001 BDC-1001 Escalating doses followed by expansion targeting HER2-expressing advanced malignancies Combination BDC-1001 plus nivolumab BDC-1001 Escalating doses followed by expansion targeting HER2-expressing advanced malignancies Combination BDC-1001 plus nivolumab Nivolumab Escalating doses followed by expansion targeting HER2-expressing advanced malignancies
- Primary Outcome Measures
Name Time Method Incidence of adverse events (AEs) and serious adverse events (SAEs) 2 years Escalation period
Incidence of potential-immune related toxicities 2 years Escalation period
Incidence and nature of dose-limiting toxicities (DLTs) up to 21 days 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 Outcome Measures
Name Time Method PK (CL) of BDC-1001 2 years Escalation period
PK (AUC0-t) of BDC-1001 2 years Escalation period
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
Progression Free Survival (PFS) 2 years Escalation and expansion periods
Disease control rate (DCR) of confirmed CR, PR, or stable disease (SD) lasting 4 or more weeks 2 years Escalation and expansion periods
Incidence of adverse events (AEs) and serious adverse events (SAEs) 2 years Expansion period
PK (AUC0-inf) of BDC-1001 2 years Escalation period
Duration of response (DOR) 2 years Escalation and expansion periods
Incidence of potential-immune related toxicities 2 years Expansion period
PK (Cmax) of BDC-1001 2 years Escalation and expansion periods
PK (Cmin) of BDC-1001 2 years Escalation and expansion periods
Incidence of anti-BDC-1001 antibodies 2 years Escalation and expansion periods
Trial Locations
- Locations (21)
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Stanford University
🇺🇸Palo Alto, California, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
South Texas Accelerated Research Therapeutics
🇺🇸San Antonio, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Institut Bergonie
🇫🇷Bordeaux, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Samsung Medical Center
🇰🇷Seoul, Gangnam-gu, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Songpa-gu, Korea, Republic of
Hospital del Mar
🇪🇸Barcelona, Cataluna, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Cataluna, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain