trastuzumab imbotolimod (BDC-1001)

This study is expected to initiate accrual in 2H 2023. For additional information, please contact Bolt Biotherapeutics at 1-650-665-9295 or info@boltbio.com.

Exploratory objectives will be pharmacodynamic biomarkers in tumor tissue and in peripheral blood, to help elucidate the mechanism of action and identify biomarkers associated with BDC-1001’s biological activity. Enrollment is ongoing in the United States, Europe, and South Korea

BDC-1001 was given IV q3w, q2w, or q1w as monotherapy (mono; n=94) and q2w or q1w with nivolumab 240mg q2w (combo; n=37). Conclusions Our novel ISAC BDC-1001 (mono/combo) led to tolerable, encouraging efficacy, translational biomarker data consistent with novel MOA in pts with pretreated HER2+ tumors, particularly at the 20mg/kg q2w RP2D. International phase 2 expansions in HER2+ colorectal, gastroesophageal, and endometrial cancers and a new phase 2 in breast cancer (BDC-1001 ± pertuzumab) have been initiated.

P2, N=66, Not yet recruiting, Bolt Biotherapeutics, Inc.

BDC-1001 incorporates a trastuzumab biosimilar (EG12014) conjugated to a proprietary TLR7/8 agonist using a non-cleavable linker and a cell membrane-impermeable payload. An international phase 1/2 study was initiated to evaluate the safety of BDC-1001 ± nivolumab (nivo) and to identify the recommended phase 2 dose (RP2D) considering PK/PD analyses and preliminary efficacy... BDC-1001 mono and combo were well-tolerated. Targeted serum exposure levels were achieved, and encouraging clinical activity was noted in heavily pretreated pts with various HER2 positive tumors, especially in the 20 mg/kg q2w cohorts. Immune biomarker changes from plasma and tumor were consistent with MoA of this ISAC.

P1/2, N=390, Recruiting, Bolt Biotherapeutics, Inc. | Trial completion date: Jul 2023 --> Oct 2026 | Trial primary completion date: Jan 2023 --> Jan 2025

Legal entity responsible for the study Bolt Biotherapeutics, Redwood City, CA. Funding Bolt Biotherapeutics, Redwood City, CA.

No abstract available

P1/2, N=390, Recruiting, Bolt Biotherapeutics, Inc. | N=607 --> 390

A 4-part, phase 1/2 dose-escalation/expansion study was initiated to evaluate BDC-1001 ± PD1 inhibitor pembrolizumab in pts with HER2-expressing solid tumors who had progressive disease on standard of care (NCT04278144) . In this first-in-human study, BDC-1001 appears to be well-tolerated up to the dose tested to date (5 mg/kg), with Cmax levels achieved as predicted by NHP modeling . Evidence of clinical activity have been observed, including in pts previously treated with anti-HER2 therapy . Dose escalation is ongoing and will be followed by combination dosing with CPI and the phase 2 component in selected tumors.

P1/2, N=607, Recruiting, Bolt Biotherapeutics, Inc. | N=390 --> 607

Exploratory objectives include pharmacokinetic parameters and pharmacodynamic biomarkers associated with drug exposure to help elucidate mechanism of action and identify biomarkers to improve selection of pts most likely to benefit from the single therapy or combination. Recruitment is ongoing (NCT04278144).

This global study is currently recruiting patients. Results N/A Conclusions N/A

Background Immune-stimulating antibody conjugates (ISACs) covalently attach immune stimulants to tumor-targeting antibodies such as trastuzumab. The molecular and cellular phenotype associated with ISAC-mediated activation is being evaluated in the on-going BDC-1001 Phase I/II clinical trial.2 ReferenceAckerman Set al, Poster# P756, SITC 20192. Phase 1/2 Study of BDC-1001 as a Single Agent and in Combination With Pembrolizumab in Patients With Advanced HER2-Expressing Solid Tumors; ClinicalTrials.gov (NCT04278144)

This global study is currently recruiting patients. Results N/A Conclusions N/A

Background Immune-stimulating antibody conjugates (ISACs) covalently attach immune stimulants to tumor-targeting antibodies such as trastuzumab. The molecular and cellular phenotype associated with ISAC-mediated activation is being evaluated in the on-going BDC-1001 Phase I/II clinical trial.2 ReferenceAckerman Set al, Poster# P756, SITC 20192. Phase 1/2 Study of BDC-1001 as a Single Agent and in Combination With Pembrolizumab in Patients With Advanced HER2-Expressing Solid Tumors; ClinicalTrials.gov (NCT04278144)

This global study is currently recruiting pts. For further information, visit ClinicalTrials.gov (NCT04278144).

P1/2, N=390, Recruiting, Bolt Biotherapeutics, Inc. | Phase classification: P1 --> P1/2

P1, N=390, Recruiting, Bolt Biotherapeutics, Inc. | Not yet recruiting --> Recruiting

P1, N=390, Not yet recruiting, Bolt Biotherapeutics, Inc.