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

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

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

Study Overview

• Status: Terminated
• Conditions: HER2-positive Breast Cancer; HER2-positive Colorectal Cancer; HER2-positive Solid Tumors; HER2-positive Gastroesophageal Cancer; HER2-positive Endometrial Cancer
• Intervention / Treatment: Drug: BDC-1001; Drug: Nivolumab

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.

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• South Korea
  • Gangnam-gu
    • Seoul, Gangnam-gu, South Korea, 06351
      • Samsung Medical Center
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital
  • Songpa-gu
    • Seoul, Songpa-gu, South Korea, 05505
      • Asan Medical Center
• Spain
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • Hospital Universitario Vall d'Hebron
    • Barcelona, Catalonia, Spain, 08003
      • Hospital del Mar
  • Madrid
    • Madrid, Madrid, Spain, 28041
      • Hospital Universitario 12 de Octubre
    • Madrid, Madrid, Spain, 28034
      • Hospital Universitario Ramon y Cajal
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bolt Biotherapeutics, Inc.
• Collaborators: Bristol-Myers Squibb
• Investigators: Study Director: Bolt Clinical Development, Bolt Biotherapeutics

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2020
• Primary Completion (Actual): December 10, 2024
• Study Completion (Actual): February 14, 2025

Study Registration Dates

• First Submitted: February 12, 2020
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (Actual): February 20, 2020

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Breast Cancer; Head and Neck Cancer; Non-Small Cell Lung Cancer; HER2; Immunotherapy; Gastric Cancer; Colorectal Cancer; Endometrial Cancer; Biliary Tract Cancer; Gastrointestinal Cancer; Stomach Cancer; Urothelial Cancer; ERBB2; Gastroesophageal junction; TLR7/8 agonist
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Respiratory Tract Diseases; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Rectal Diseases; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Biliary Tract Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Lung Neoplasms; Genital Neoplasms, Female; Skin Diseases; Breast Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Uterine Neoplasms; Skin and Connective Tissue Diseases; Stomach Neoplasms; Biliary Tract Neoplasms; Colorectal Neoplasms; Breast Neoplasms; Gastrointestinal Neoplasms; Carcinoma, Non-Small-Cell Lung; Head and Neck Neoplasms; Endometrial Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab
• Other Study ID Numbers: BBI-20201001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No