BI-1607 in Combination with Trastuzumab in Subjects with HER2-positive Advanced Solid Tumors

NCT ID: NCT05555251

Last Updated: 2024-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-28

Study Completion Date

2024-02-07

Brief Summary

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HER2+ breast and gastric cancer patients' survival is significantly improved by trastuzumab alone or in combination with chemotherapy. However, many patients remain uncured and develop resistance to trastuzumab resulting in relapse or progression of the disease. BI-1607, a human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) targets CD32b (Fc Gamma Receptor IIB), it is intended to enhance the efficacy and overcome resistance to existing cancer treatments such as trastuzumab.

This is a Phase 1/2a, first-in-human, open-label, multicenter, dose-escalation, consecutive-cohort study of BI-1607 in combination with trastuzumab in subjects with HER2+ advanced solid tumors whose tumor has progressed after standard therapy.

Detailed Description

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This is a Phase 1/2a, first-in-human, open-label, multicenter, dose-escalation, consecutive-cohort study of BI-1607 in combination with trastuzumab in subjects with HER2+ advanced solid tumors whose tumor has progressed after standard therapy.

The Phase 1 part of the trial is a dose escalation study of BI-1607 combined with trastuzumab in HER2+ advanced or metastatic solid tumors, the aim is to assess safety and tolerability and to determine the recommended phase II dose of BI-1607 in combination with trastuzumab.

The selected dose of BI-1607 will be studied in a subsequent Phase 2a part of the trial along with trastuzumab in 2 open-label, expansion cohorts of 15 evaluable subjects each. The first cohort will enroll subjects with locally advanced or metastatic HER2+ breast cancer, and the second will recruit subjects with HER2+ metastatic gastric or gastroesophageal junction adenocarcinoma. The aim of the phase 2a is to collect additional safety data to further support the recommended dose, and to detect early signs of clinical activity.

Conditions

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HER2-positive Breast Cancer HER2-positive Gastric Cancer HER2-positive Metastatic Breast Cancer Metastatic Gastroesophageal Junction Adenocarcinoma Metastatic Gastric Adenocarcinoma

Keywords

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HER2-positive solid tumours

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

This is a Phase 1/2a, FIH, open-label, multicenter, dose-escalation, consecutive-cohort study of BI-1607 in combination with trastuzumab.

The study will consist of 2 Phases:

* Phase 1, the dose-escalation part of the study, the aim of which is to assess safety and tolerability and to determine the RP2D of BI-1607 in combination with trastuzumab in subjects with HER2+ advanced solid tumors.
* Phase 2a, comprising of 2 separate expansion cohorts treated at the RP2D of BI-1607 in combination with trastuzumab in subjects with locally advanced or metastatic HER2+ breast cancer and subjects with HER2+ metastatic gastric or gastroesophageal junction adenocarcinoma. The aim of Phase 2a is to collect additional safety data to further support RP2D, and to detect early signs of clinical activity.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase I -Dose escalation

Dose escalation study of BI-1607 combined with trastuzumab in HER2+ advanced or metastatic solid tumors.

Group Type EXPERIMENTAL

BI-1607

Intervention Type DRUG

administered at different doses in Phase I by intravenous infusions every 3 weeks.

Trastuzumab

Intervention Type DRUG

administered at 8mg/kg for the first infusion and at 6mg/kg in subsequent infusions by intravenous infusions every 3 weeks.

Phase 2a - Expansion cohorts

Dose expansion study of BI-1607 combined with trastuzumab in cohort 1: HER2 positive locally advanced or metastatic HER2+ breast cancer and cohort 2: metastatic gastric or gastroesophageal junction adenocarcinoma

Group Type EXPERIMENTAL

BI-1607

Intervention Type DRUG

administered at the recommended dose in Phase 2a by intravenous infusions every 3 weeks.

Trastuzumab

Intervention Type DRUG

administered at 8mg/kg for the first infusion and at 6mg/kg in subsequent infusions by intravenous infusions every 3 weeks.

Interventions

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BI-1607

administered at different doses in Phase I by intravenous infusions every 3 weeks.

Intervention Type DRUG

BI-1607

administered at the recommended dose in Phase 2a by intravenous infusions every 3 weeks.

Intervention Type DRUG

Trastuzumab

administered at 8mg/kg for the first infusion and at 6mg/kg in subsequent infusions by intravenous infusions every 3 weeks.

Intervention Type DRUG

Other Intervention Names

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Herceptin

Eligibility Criteria

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Inclusion Criteria

* Is willing and able to provide written informed consent for the trial.
* Is ≥18 years of age on day of signing informed consent.
* Has received standard of care or is intolerant to standard of care antineoplastic therapy. Subjects who are intolerant to trastuzumab cannot be enrolled in the study.
* Has at least 1 measurable disease lesion as defined by RECIST v1.1 criteria.
* Has a locally confirmed HER2+ tumor.
* Must have progressive disease after the last line of treatment. In addition, subjects must have received the following previous lines of treatment:

1. Prior lines of treatment including trastuzumab and chemotherapy.
2. At least one prior line of treatment with an antibody-drug conjugate (ADC) (eg, trastuzumab-emtansine \[TDM-1, or trastuzumab-deruxtecan\]).

Exclusion Criteria

* Needs doses of prednisolone \>10 mg daily (or equipotent doses of other corticosteroids) while on the trial other than as premedication.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has cardiac or renal amyloid light-chain amyloidosis.
* Has had clinically significant lung disease requiring systemic corticosteroid treatment within the last 6 months of enrollment.
* Has an active, known, or suspected autoimmune disease.
* Is at high medical risk because of nonmalignant systemic disease including severe active infections on treatment with antibiotics, antifungals, or antivirals.
* Has presence of chronic graft versus host disease.
* Has had an allogenic tissue/solid organ transplant.
* Has uncontrolled or significant cardiovascular disease.
* Has a known additional malignancy of another type, except for adequately treated cone-biopsied carcinoma in situ (eg, breast carcinoma, cervical cancer in situ), adequately controlled superficial bladder cancer, and basal or squamous cell carcinoma of the skin.
* Has a diagnosis of primary or acquired immunodeficiency disorder or is taking any other form of immunosuppressive therapy.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BioInvent International AB

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andres McAllister, MD, PhD

Role: STUDY_DIRECTOR

BioInvent International AB

Locations

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Evang. Kliniken Essen-Mitte

Essen, , Germany

Site Status

Krankenhaus Nordwest

Frankfurt, , Germany

Site Status

Hospital Vall d'Hebron

Barcelona, , Spain

Site Status

Complejo hospitalario Ruber Juan Bravo

Madrid, , Spain

Site Status

Churchill Hospital

Oxford, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

Countries

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Germany Spain United Kingdom

References

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Cortes J, Priego A, Garralda E, Rojas K, Lord SR, Goetze TO, Kuemmel S, Crabb SJ, Parra-Guillen ZP, Borggren M, Karlsson I, Lindahl D, Martensson L, Oldham R, Ropenga A, Teige I, Wallin J, Frendeus B, McAllister A. A First-in-Class Monoclonal Antibody (BI-1607) Targeting FcgammaRIIB: Preclinical Data and First-in-Human Studies in Patients with HER2-Positive Advanced Solid Tumors. Clin Cancer Res. 2025 Oct 10. doi: 10.1158/1078-0432.CCR-25-1348. Online ahead of print.

Reference Type DERIVED
PMID: 41071338 (View on PubMed)

Other Identifiers

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21-BI-1607-01

Identifier Type: -

Identifier Source: org_study_id