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

NCT05555251 | Terminated Phase 1 DMC

• 1 other identifier: 21-BI-1607-01
• Study Type: interventional
• Target: 18
• Locations: 3 countries
• Sites: 6

Brief Summary

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.

Conditions

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

Keywords

HER2-positive; solid tumours

Outcome Measures

Primary Outcomes (2)

• Assessment of the safety and tolerability profile of BI-1607 in combination with trastuzumab

  Adverse events (AEs) and serious adverse events (SAEs) (graded according to the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0) and their causality in relation to BI-1607 or to the combination with trastuzumab

  End of treatment visit or 30 days after last dose of study drug.

• Identify Dose limiting toxicities, determine the maximum tolerate dose of BI-1607 and propose a recommended Phase 2 dose (RP2D) for evaluation of BI-1607 in combination with trastuzumab.

  Occurrence of DLTs

  22 days

Secondary Outcomes (4)

• Assessment of the pharmacokinetic (PK) profile of BI-1607 when administered every 3 weeks in combination with trastuzumab

  90 days after the last dose of BI-1607

• Assessment of the immunogenicity of BI-1607 when administered in combination with trastuzumab

  90 days after the last dose of BI-1607

• Assessment of the CD32b receptor occupancy (RO) of BI-1607 on B cells when administered in combination with trastuzumab

  30 days after the last dose of BI-1607

• Assessment of the possible antitumor activity of BI-1607 in combination with trastuzumab

  1 year after the last treatment

Other Outcomes (3)

• Exploratory: investigate expression levels of Fc receptors, and other immunological markers on immune cells infiltrating the tumor

  1 day

• Exploratory: investigate the genetic background of subjects with respect to FcgammaR isoforms and explore a potential correlation of the genetic background with clinical responses

  1 day

• Exploratory: explore any exposure-response and/or exposure-safety relationship between BI-1607 serum concentrations and clinical outcome

  1 day

Study Arms (2)

Phase I -Dose escalation

EXPERIMENTAL

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

Drug: BI-1607; Drug: Trastuzumab

Phase 2a - Expansion cohorts

EXPERIMENTAL

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

Drug: BI-1607; Drug: Trastuzumab

Interventions

BI-1607 DRUG

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

Phase I -Dose escalation

Trastuzumab DRUG

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

Also known as: Herceptin

Phase 2a - Expansion cohorts; Phase I -Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• BioInvent International AB: lead

Study Sites (6)

Evang. Kliniken Essen-Mitte

Essen, 45136, Germany

Location

Krankenhaus Nordwest

Frankfurt, 60488, Germany

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Complejo hospitalario Ruber Juan Bravo

Madrid, 28034, Spain

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

• 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 mAb (BI-1607) Targeting FcgammaRIIB: Preclinical Data and First-in-Human Studies in Patients with HER2-Positive Advanced Solid Tumors. Clin Cancer Res. 2025 Dec 1;31(23):4953-4963. doi: 10.1158/1078-0432.CCR-25-1348.

  PMID: 41071338 DERIVED

MeSH Terms

Interventions

Trastuzumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Andres McAllister, MD, PhD

  BioInvent International AB

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 22, 2022
• First Posted: September 26, 2022
• Study Start: July 28, 2022
• Primary Completion: February 7, 2024
• Study Completion: February 7, 2024
• Last Updated: December 16, 2024

Record last verified: 2024-12

Locations

DE (2); ES (2); GB (2)