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

HER2-positive Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04278144
• Other study ID #: BBI-20201001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: February 24, 2020
• Est. completion date: October 31, 2026

Study information

• Verified date: May 2024
• Source: Bolt Biotherapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 390
• Est. completion date: October 31, 2026
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Endometrial Neoplasms
• HER2-positive Breast Cancer
• HER2-positive Solid Tumors

Intervention

Drug:
• BDC-1001
Immune stimulating antibody conjugate (ISAC), consisting of an anti-HER2 monoclonal antibody conjugated to a TLR 7/8 dual agonist
• Nivolumab
Programmed death receptor-1 (PD 1)-blocking antibody

Locations

Country	Name	City	State
France	Institut Bergonie	Bordeaux
France	Institut Paoli Calmettes	Marseille
France	Hopital Pitie-Salpetriere	Paris
France	Centre Eugene Marquis	Rennes
France	Institut Gustave Roussy	Villejuif
Italy	Instituto Clinico Humanitas	Milan	Lombardia
Italy	Istituto Nazionale Tumori IRCCS Fondazione G. Pascale	Napoli	Campania
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul	Songpa-gu
Korea, Republic of	Samsung Medical Center	Seoul	Gangnam-gu
Spain	Hospital del Mar	Barcelona	Cataluna
Spain	Hospital Universitario Vall d'Hebron	Barcelona	Cataluna
Spain	Institut Catala D'Oncologia	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	START Midwest	Grand Rapids	Michigan
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Stanford University	Palo Alto	California
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Bolt Biotherapeutics, Inc.	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  France,  Italy,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events (AEs) and serious adverse events (SAEs)	Escalation period	2 years
Primary	Incidence and nature of dose-limiting toxicities (DLTs)	Escalation period	up to 21 days
Primary	Incidence of potential-immune related toxicities	Escalation period	2 years
Primary	Maximum tolerable dose (MTD) or a tolerated dose below MTD	Escalation period	2 years
Primary	Objective response rate (ORR) of confirmed complete or partial responses (CR, PR)	Expansion period	2 years
Secondary	PK (Cmax) of BDC-1001	Escalation and expansion periods	2 years
Secondary	PK (Cmin) of BDC-1001	Escalation and expansion periods	2 years
Secondary	PK (AUC0-t) of BDC-1001	Escalation period	2 years
Secondary	PK (AUC0-inf) of BDC-1001	Escalation period	2 years
Secondary	PK (CL) of BDC-1001	Escalation period	2 years
Secondary	PK (Vz) of BDC-1001	Escalation period	2 years
Secondary	PK (t1/2) of BDC-1001	Escalation period	2 years
Secondary	Objective response rate (ORR) using RECIST 1.1	Escalation period	2 years
Secondary	Duration of response (DOR)	Escalation and expansion periods	2 years
Secondary	Disease control rate (DCR) of confirmed CR, PR, or stable disease (SD) lasting 4 or more weeks	Escalation and expansion periods	2 years
Secondary	Progression Free Survival (PFS)	Escalation and expansion periods	2 years
Secondary	Incidence of anti-BDC-1001 antibodies	Escalation and expansion periods	2 years
Secondary	Incidence of adverse events (AEs) and serious adverse events (SAEs)	Expansion period	2 years
Secondary	Incidence of potential-immune related toxicities	Expansion period	2 years