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BI-1607 in Combination With Trastuzumab in Subjects With HER2-positive Advanced Solid Tumors (CONTRAST)

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ClinicalTrials.gov Identifier: NCT05555251
Recruitment Status : Recruiting
First Posted : September 26, 2022
Last Update Posted : November 17, 2022
Sponsor:
Information provided by (Responsible Party):
BioInvent International AB

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.


Condition or disease Intervention/treatment Phase
HER2-positive Breast Cancer HER2-positive Gastric Cancer HER2-positive Metastatic Breast Cancer Metastatic Gastroesophageal Junction Adenocarcinoma Metastatic Gastric Adenocarcinoma Drug: BI-1607 Drug: Trastuzumab Phase 1 Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 116 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2a Open-label Clinical Trial of BI-1607, an Fc-Engineered Monoclonal Antibody to CD32b (FcγRIIB), in Combination With Trastuzumab in Subjects With HER2-positive Advanced Solid Tumors
Actual Study Start Date : July 28, 2022
Estimated Primary Completion Date : March 2025
Estimated Study Completion Date : December 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Trastuzumab

Arm Intervention/treatment
Experimental: Phase I -Dose escalation
Dose escalation study of BI-1607 combined with trastuzumab in HER2+ advanced or metastatic solid tumors.
Drug: BI-1607
administered at different doses in Phase I by intravenous infusions every 3 weeks.

Drug: Trastuzumab
administered at 8mg/kg for the first infusion and at 6mg/kg in subsequent infusions by intravenous infusions every 3 weeks.
Other Name: Herceptin

Experimental: 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
Drug: BI-1607
administered at the recommended dose in Phase 2a by intravenous infusions every 3 weeks.

Drug: Trastuzumab
administered at 8mg/kg for the first infusion and at 6mg/kg in subsequent infusions by intravenous infusions every 3 weeks.
Other Name: Herceptin




Primary Outcome Measures :
  1. Assessment of the safety and tolerability profile of BI-1607 in combination with trastuzumab [ Time Frame: End of treatment visit or 30 days after last dose of study drug. ]
    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

  2. 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. [ Time Frame: 22 days ]
    Occurrence of DLTs


Secondary Outcome Measures :
  1. Assessment of the pharmacokinetic (PK) profile of BI-1607 when administered every 3 weeks in combination with trastuzumab [ Time Frame: 90 days after the last dose of BI-1607 ]
    The PK parameters will include area under the serum concentration-time curve, maximum concentration, time to maximum concentration, and terminal half-life

  2. Assessment of the immunogenicity of BI-1607 when administered in combination with trastuzumab [ Time Frame: 90 days after the last dose of BI-1607 ]
    Antidrug antibody response to BI-1607 in blood serum

  3. Assessment of the CD32b receptor occupancy (RO) of BI-1607 on B cells when administered in combination with trastuzumab [ Time Frame: 30 days after the last dose of BI-1607 ]
    RO on circulating B lymphocytes

  4. Assessment of the possible antitumor activity of BI-1607 in combination with trastuzumab [ Time Frame: 1 year after the last treatment ]
    Best tumor response, objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, progression-free survival (PFS), time to response, duration of response (DOR) and OS


Other Outcome Measures:
  1. Exploratory: investigate expression levels of Fc receptors, and other immunological markers on immune cells infiltrating the tumor [ Time Frame: 1 day ]
    Expression levels of Fc receptors (eg, CD32b) and other markers of immunological activity using immunohistochemistry (IHC) and/or nucleotide-based assays using tissue samples

  2. Exploratory: investigate the genetic background of subjects with respect to FcgammaR isoforms and explore a potential correlation of the genetic background with clinical responses [ Time Frame: 1 day ]
    Determination of Fcgamma receptor isoforms using nucleotide-based assays on genetic material extracted from whole blood

  3. Exploratory: explore any exposure-response and/or exposure-safety relationship between BI-1607 serum concentrations and clinical outcome [ Time Frame: 1 day ]
    Correlation of BI-1607 PK and antitumor activity measures, as well as to safety measures of interest



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main 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]).

Main 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05555251


Contacts
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Contact: Anna Ropenga, PhD +46462868550 anna.ropenga@bioinvent.com
Contact: Andres McAllister, MD, PhD +46462868550 andres.mcallister@bioinvent.com

Locations
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Germany
Evang. Kliniken Essen-Mitte Not yet recruiting
Essen, Germany, 45136
Principal Investigator: Sherko Kuemmel, MD         
Krankenhaus Nordwest Not yet recruiting
Frankfurt, Germany, 60488
Principal Investigator: Thorsten Goetze, MD         
Spain
Hospital Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Principal Investigator: Elena Garralda Cabanas, MD         
Complejo hospitalario Ruber Juan Bravo Recruiting
Madrid, Spain, 28034
Principal Investigator: Javier Cortes Castan, MD         
United Kingdom
Churchill Hospital Recruiting
Oxford, United Kingdom, OX3 7LE
Principal Investigator: Simon Lord, MD         
Southampton General Hospital Not yet recruiting
Southampton, United Kingdom, SO16 6YD
Principal Investigator: Simon Crabb, MD         
Sponsors and Collaborators
BioInvent International AB
Investigators
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Study Director: Andres McAllister, MD, PhD BioInvent International AB
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Responsible Party: BioInvent International AB
ClinicalTrials.gov Identifier: NCT05555251    
Other Study ID Numbers: 21-BI-1607-01
First Posted: September 26, 2022    Key Record Dates
Last Update Posted: November 17, 2022
Last Verified: September 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by BioInvent International AB:
HER2-positive
solid tumours
Additional relevant MeSH terms:
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Breast Neoplasms
Adenocarcinoma
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Trastuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents