Clinical trial NCT04278144: A First-in-human Study Using BDC-1001 As a Single Agent and in Combination with Nivolumab in Advanced HER2-Expressing Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: HER2-positive Solid Tumors
HER2-positive Breast Cancer
HER2-positive Colorectal Cancer
HER2-positive Gastroesophageal Cancer
HER2-positive Endometrial Cancer
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
Lead sponsor: Bolt Biotherapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2020-02-20
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multiple ascending dose and dose-expansion of BDC-1001 administered as a single agent or in combination with nivolumab.
Primary purpose: TREATMENT

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.

Eligibility 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/exclusion criteria may apply.

Primary outcomes:
measure: Incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 2 years
measure: Incidence and nature of dose-limiting toxicities (DLTs)
timeFrame: up to 21 days
measure: Incidence of potential-immune related toxicities
timeFrame: 2 years
measure: Maximum tolerable dose (MTD) or a tolerated dose below MTD
timeFrame: 2 years
measure: Objective response rate (ORR) of confirmed complete or partial responses (CR, PR)
timeFrame: 2 years
Secondary outcomes:
measure: PK (Cmax) of BDC-1001
timeFrame: 2 years
measure: PK (Cmin) of BDC-1001
timeFrame: 2 years
measure: PK (AUC0-t) of BDC-1001
timeFrame: 2 years
measure: PK (AUC0-inf) of BDC-1001
timeFrame: 2 years
measure: PK (CL) of BDC-1001
timeFrame: 2 years
measure: PK (Vz) of BDC-1001
timeFrame: 2 years
measure: PK (t1/2) of BDC-1001
timeFrame: 2 years
measure: Objective response rate (ORR) using RECIST 1.1
timeFrame: 2 years
measure: Duration of response (DOR)
timeFrame: 2 years
measure: Disease control rate (DCR) of confirmed CR, PR, or stable disease (SD) lasting 4 or more weeks
timeFrame: 2 years
measure: Progression Free Survival (PFS)
timeFrame: 2 years
measure: Incidence of anti-BDC-1001 antibodies
timeFrame: 2 years
measure: Incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 2 years
measure: Incidence of potential-immune related toxicities
timeFrame: 2 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Bordeaux
country: France
facility: Institut Bergonie
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gangnam-gu
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Songpa-gu
city: Barcelona
country: Spain
facility: Hospital del Mar
state: Cataluna
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
state: Cataluna
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
Study officials:
affiliation: Bolt Biotherapeutics
name: Bolt Clinical Development
role: STUDY_DIRECTOR
References: