Back to resultsBI-1607 in Combination With Trastuzumab in Subjects With HER2-positive Advanced Solid Tumors (CONTRAST)
Primary Purpose
HER2-positive Breast Cancer, HER2-positive Gastric Cancer, HER2-positive Metastatic Breast Cancer
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BI-1607
BI-1607
Trastuzumab
Sponsored by
About this trial
This is an interventional treatment trial for HER2-positive Breast Cancer focused on measuring HER2-positive, solid tumours
Eligibility 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:
- 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]).
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.
Sites / Locations
- Evang. Kliniken Essen-Mitte
- Krankenhaus Nordwest
- Hospital Vall d'HebronRecruiting
- Complejo hospitalario Ruber Juan BravoRecruiting
- Churchill HospitalRecruiting
- Southampton General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Phase I -Dose escalation
Phase 2a - Expansion cohorts
Arm Description
Dose escalation study of BI-1607 combined with trastuzumab in HER2+ advanced or metastatic solid tumors.
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
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
Assessment of the pharmacokinetic (PK) profile of BI-1607 when administered every 3 weeks in combination with trastuzumab
The PK parameters will include area under the serum concentration-time curve, maximum concentration, time to maximum concentration, and terminal half-life
Assessment of the immunogenicity of BI-1607 when administered in combination with trastuzumab
Antidrug antibody response to BI-1607 in blood serum
Assessment of the CD32b receptor occupancy (RO) of BI-1607 on B cells when administered in combination with trastuzumab
RO on circulating B lymphocytes
Assessment of the possible antitumor activity of BI-1607 in combination with trastuzumab
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
Full Information
NCT ID
NCT05555251
First Posted
September 22, 2022
Last Updated
November 15, 2022
Sponsor
BioInvent International AB
1. Study Identification
Unique Protocol Identification Number
NCT05555251
Brief Title
BI-1607 in Combination With Trastuzumab in Subjects With HER2-positive Advanced Solid Tumors
Acronym
CONTRAST
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 28, 2022 (Actual)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
December 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioInvent International AB
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
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)
Allocation
Non-Randomized
Enrollment
116 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Phase I -Dose escalation
Arm Type
Experimental
Arm Description
Dose escalation study of BI-1607 combined with trastuzumab in HER2+ advanced or metastatic solid tumors.
Arm Title
Phase 2a - Expansion cohorts
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
BI-1607
Intervention Description
administered at different doses in Phase I by intravenous infusions every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
BI-1607
Intervention Description
administered at the recommended dose in Phase 2a by intravenous infusions every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Other Intervention Name(s)
Herceptin
Intervention Description
administered at 8mg/kg for the first infusion and at 6mg/kg in subsequent infusions by intravenous infusions every 3 weeks.
Primary Outcome Measure Information:
Title
Assessment of the safety and tolerability profile of BI-1607 in combination with trastuzumab
Description
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
Time Frame
End of treatment visit or 30 days after last dose of study drug.
Title
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.
Description
Occurrence of DLTs
Time Frame
22 days
Secondary Outcome Measure Information:
Title
Assessment of the pharmacokinetic (PK) profile of BI-1607 when administered every 3 weeks in combination with trastuzumab
Description
The PK parameters will include area under the serum concentration-time curve, maximum concentration, time to maximum concentration, and terminal half-life
Time Frame
90 days after the last dose of BI-1607
Title
Assessment of the immunogenicity of BI-1607 when administered in combination with trastuzumab
Description
Antidrug antibody response to BI-1607 in blood serum
Time Frame
90 days after the last dose of BI-1607
Title
Assessment of the CD32b receptor occupancy (RO) of BI-1607 on B cells when administered in combination with trastuzumab
Description
RO on circulating B lymphocytes
Time Frame
30 days after the last dose of BI-1607
Title
Assessment of the possible antitumor activity of BI-1607 in combination with trastuzumab
Description
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
Time Frame
1 year after the last treatment
Other Pre-specified Outcome Measures:
Title
Exploratory: investigate expression levels of Fc receptors, and other immunological markers on immune cells infiltrating the tumor
Description
Expression levels of Fc receptors (eg, CD32b) and other markers of immunological activity using immunohistochemistry (IHC) and/or nucleotide-based assays using tissue samples
Time Frame
1 day
Title
Exploratory: investigate the genetic background of subjects with respect to FcgammaR isoforms and explore a potential correlation of the genetic background with clinical responses
Description
Determination of Fcgamma receptor isoforms using nucleotide-based assays on genetic material extracted from whole blood
Time Frame
1 day
Title
Exploratory: explore any exposure-response and/or exposure-safety relationship between BI-1607 serum concentrations and clinical outcome
Description
Correlation of BI-1607 PK and antitumor activity measures, as well as to safety measures of interest
Time Frame
1 day
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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:
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]).
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anna Ropenga, PhD
Phone
+46462868550
Email
anna.ropenga@bioinvent.com
First Name & Middle Initial & Last Name or Official Title & Degree
Andres McAllister, MD, PhD
Phone
+46462868550
Email
andres.mcallister@bioinvent.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andres McAllister, MD, PhD
Organizational Affiliation
BioInvent International AB
Official's Role
Study Director
Facility Information:
Facility Name
Evang. Kliniken Essen-Mitte
City
Essen
ZIP/Postal Code
45136
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sherko Kuemmel, MD
Facility Name
Krankenhaus Nordwest
City
Frankfurt
ZIP/Postal Code
60488
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thorsten Goetze, MD
Facility Name
Hospital Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elena Garralda Cabanas, MD
Facility Name
Complejo hospitalario Ruber Juan Bravo
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Javier Cortes Castan, MD
Facility Name
Churchill Hospital
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Simon Lord, MD
Facility Name
Southampton General Hospital
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Simon Crabb, MD
12. IPD Sharing Statement
Learn more about this trial
BI-1607 in Combination With Trastuzumab in Subjects With HER2-positive Advanced Solid Tumors
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