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

Phase 2TerminatedNCT04278144

Bolt Biotherapeutics, Inc.175 enrolled

Overview

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

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

175

Conditions

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

Interventions

BDC-1001DRUG

Immune stimulating antibody conjugate (ISAC), consisting of an anti-HER2 monoclonal antibody conjugated to a TLR 7/8 dual agonist

NivolumabDRUG

Programmed death receptor-1 (PD 1)-blocking antibody

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (21)

Stanford University

Palo Alto, California, United States

Outcomes

Primary Outcomes

Incidence of adverse events (AEs) and serious adverse events (SAEs)

Escalation period

Time frame: 2 years

Incidence and nature of dose-limiting toxicities (DLTs)

Escalation period

Time frame: up to 21 days

Incidence of potential-immune related toxicities

Escalation period

Time frame: 2 years

Maximum tolerable dose (MTD) or a tolerated dose below MTD

Escalation period

Time frame: 2 years

Objective response rate (ORR) of confirmed complete or partial responses (CR, PR)

Expansion period

Time frame: 2 years

Secondary Outcomes

PK (Cmax) of BDC-1001

Escalation and expansion periods

Time frame: 2 years

PK (Cmin) of BDC-1001

Escalation and expansion periods

Time frame: 2 years

PK (AUC0-t) of BDC-1001

Escalation period

Time frame: 2 years

PK (AUC0-inf) of BDC-1001

Escalation period

Time frame: 2 years

PK (CL) of BDC-1001

Data from ClinicalTrials.gov

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