A Study of BB-1701 in Previously Treated Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive or HER2-low Unresectable or Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title:

An Open-label, Multicenter, Phase 2 Dose Optimization and Expansion Study to Evaluate the Safety and Efficacy of BB-1701, an Anti-human Epidermal Growth Factor Receptor 2 (Anti-HER2) Antibody-drug Conjugate (ADC), in Previously Treated Subjects With HER2-positive or HER2-low Unresectable or Metastatic Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06188559
• Other study ID #: BB-1701-G000-205
• Secondary ID: 2023-506866-30
• Status: Recruiting
• Phase: Phase 2
• Start date: April 10, 2024
• Est. completion date: October 26, 2026

Study information

• Verified date: May 2024
• Source: Eisai Inc.
• Contact: Eisai Medical Information
• Phone: 1-888-274-2378
• Email: esi_oncmedinfo[@]eisai.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of the Dose Optimization (Part 1) of this study is to assess the safety and tolerability of BB-1701 and to determine the recommended dose (RD) of BB-1701 for Dose Expansion (Part 2). The primary purpose of Dose Expansion (Part 2) is to assess the antitumor activity of BB-1701 at RD in the selected population(s) of breast cancer (BC).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 135
• Est. completion date: October 26, 2026
• Est. primary completion date: October 26, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Male or female, aged >=18 years at the time of informed consent.

• Metastatic or unresectable BC that is histologically confirmed to be either HER2-positive (defined as an immunohistochemistry [IHC] status of 3+, or a positive in situ hybridization [ISH] test [fluorescence, chromogenic, or silver-enhanced ISH] if IHC status is 2+) or HER2-low (defined as an IHC status of 1+, or 2+ and negative ISH) per the American Society of Clinical Oncology/College of American Pathology guidelines as documented prior to trastuzumab deruxtecan (T-DXd) treatment.

• Must have previously received T-DXd.

• Sufficient tumor tissue is required for HER2 status testing at a central laboratory.

• Measurable disease per RECIST 1.1 as assessed by the investigator. Participants with bone only disease may be eligible if there is a measurable soft tissue component associated with the bone lesion.

• Must have previously received at least 1 but no more than 3 prior chemotherapy-based regimes in the unresectable or metastatic setting. If recurrence occurred during or within 6 months of (neo) adjuvant chemotherapy, this would count as 1 line of chemotherapy.

• If HR-positive HER2-low BC, must have previously received endocrine therapy and is not expected to further benefit from it.

• ECOG PS 0 or 1.

• Life expectancy of at least 3 months.

• Adequate organ function and laboratory parameters.

Exclusion Criteria

• Presence of brain or subdural metastases, unless participant has completed local therapy and has discontinued the use of corticosteroids for this indication for at least 2 weeks prior to starting treatment in this study.

• Diagnosed with meningeal carcinomatosis.

• Received anticancer therapy (chemotherapy or other systemic anticancer therapies, immunotherapy, radiation therapy, etc) or an investigational drug or device within the past 28 days or 5 half-lives, whichever is shorter.

• Prior treatment with eribulin.

• Any prior allergic reactions of Grade >=3 to monoclonal antibodies or contraindication to the receipt of corticosteroids or any of the excipients (investigators should refer to the prescribing information for the selected corticosteroid).

• Residual toxic effects of prior therapies or surgical procedures that is Grade >=2 (except alopecia or anemia).

• Grade >=2 peripheral neuropathy or history of Grade >=3 peripheral neuropathy or discontinued any prior treatment due to peripheral neuropathy.

• Active pneumonitis/interstitial lung disease (ILD) or any clinically significant lung disease (example, chronic obstructive pulmonary disease), history of Grade >=2 pneumonitis/ILD, or received radiotherapy to lung fields within 12 months of Cycle 1 Day 1 of study treatment.

• Congestive heart failure greater than (>) New York Heart Association Class II or left ventricular ejection fraction (LVEF) less than (<) 50 percent (%) measured by multigated acquisition scan (MUGA) or echocardiogram.

• Has a corrected QT interval prolongation per Fridericia formula (QTcF) >470 millisecond (ms) (for both males and females) based on screening triplicate 12-lead ECG.

• Concomitant active infection requiring systemic treatment, except:

• If known to be human immunodeficiency virus (HIV)-positive, must be on anti-HIV therapy for at least 4 weeks and have a clusters of differentiation 4+ T-cell (CD4+) count >=350 cells per microliter (cells/mcL) and an HIV viral load <400 copies per milliliter (copies/mL).

• If meets the criteria for anti-hepatitis B virus (HBV) therapy, must agree to take anti-HBV therapy, if known to be HBV-positive as defined by positive hepatitis B surface antigen or hepatitis B core antibody. HBV viral load must be undetectable.

• If known to be hepatitis C virus (HCV)-positive must have completed curative therapy for HCV. HCV viral load must be undetectable.

• Known history of active bacillus tuberculosis (TB).

• Any medical or other condition which, in the opinion of the investigator would preclude the participant's participation in the clinical study.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• BB-1701
BB-1701 will be administered as an intravenous infusion, every 3 weeks (21-day cycle).

Locations

Country	Name	City	State
Japan	Sagara Hospital, Social Medical Corporation Hakuaikai	Kagoshima Shi	Kagoshima
Japan	The Cancer Institute Hospital of Japanese Foundation for Cancer Research	Koto Ku	Tokyo
Japan	Nagoya University Hospital	Nagoya Shi	Aichi
Japan	Okayama University Hospital	Okayama Shi	Okayama
Japan	Tohoku University Hospital	Sendai Shi	Miyagi
Japan	Showa University	Shinagawa Ku	Tokyo
Japan	Kanagawa Cancer Center	Yokohama Shi	Kanagawa
United States	New Mexico Oncology Hematology Consultants	Albuquerque	New Mexico
United States	Mission Blood and Cancer	Des Moines	Iowa
United States	Astera Cancer Care	East Brunswick	New Jersey
United States	Fort Wayne Medical Oncology & Hematology	Fort Wayne	Indiana
United States	NHO Revive Research Institute LLC	Lincoln	Nebraska
United States	Cancer and Blood Specialty Clinic	Los Alamitos	California
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Nebraska Cancer Specialist	Omaha	Nebraska
United States	Northwest Medical Specialties	Puyallup	Washington
United States	Oregon Oncology Specialists	Salem	Oregon
United States	Avera Cancer Institute	Sioux Falls	South Dakota

Sponsors (2)

Lead Sponsor	Collaborator
Eisai Inc.	Bliss Biopharmaceutical (Hangzhou) Co., Ltd

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1, Dose Optimization: Number of Participants With Adverse Events (AEs)	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product; Any new disease or exacerbation of an existing disease; any deterioration in non-protocol-required measurements of a laboratory value or other clinical test (example, electrocardiogram [ECG] or x-ray) that results in symptoms, a change in treatment, or discontinuation of study drug; Recurrence of an intermittent medical condition (example, headache) not present pretreatment (baseline); An abnormal laboratory test result should be considered an AE if the identified laboratory abnormality leads to any type of intervention, withdrawal of study drug, or withholding of study drug, whether prescribed in the protocol or not. An AE does not necessarily have a causal relationship with the medicinal product.	Baseline up to 35 months
Primary	Part 1, Dose Optimization: Number of Participants With Clinically Significant Laboratory Values	Clinical laboratory parameters includes hematology, chemistry, and urinalysis.	Baseline up to 35 months
Primary	Part 1, Dose Optimization: Number of Participants With Clinically Significant Vital Sign Values	Vital sign parameters includes systolic and diastolic blood pressure (BP), pulse, respiratory rate, body temperature.	Baseline up to 35 months
Primary	Part 1, Dose Optimization: Number of Participants With Clinically Significant 12-lead ECGs Values	Number of participants with clinically significant 12-lead ECGs values will be reported.	Baseline up to 35 months
Primary	Part 1, Dose Optimization: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)	Number of participants with ECOG PS will be reported.	Baseline up to 35 months
Primary	Part 1, Dose Optimization: Objective Response Rate (ORR)	ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or confirmed partial response (PR) by investigator assessment per Response Evaluation Criteria for Solid Tumours (RECIST) version (v) 1.1.	From date of first dose of study drug until first documentation of CR or PR (up to 35 months)
Primary	Part 2, Dose Expansion: Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Assessment per RECIST v1.1	ORR is defined as the percentage of participants achieving a confirmed CR or confirmed PR based on BICR assessment per RECIST v1.1.	From date of first dose of study drug until first documentation of CR or PR (up to 35 months)
Secondary	Part 1, Dose Optimization: Duration of Response (DOR)	DOR defined as the time from the onset date of documented CR or PR for confirmed responses by investigator per RECIST v1.1 to the date of disease progression (PD) or death, whichever occurs first.	From the date of documented CR or PR to the date of PD or death, whichever occurs first (up to 35 months)
Secondary	Part 1, Dose Optimization: Progression-free Survival (PFS)	PFS is defined as the time from the date of first dose to the date of the first documentation of PD by investigator per RECIST v1.1 or death, whichever occurs first.	From the date of first dose to the date of the first documentation of PD or death, whichever occurs first (up to 35 months)
Secondary	Part 1, Dose Optimization: Overall Survival (OS)	Overall survival (OS) is defined as the time from the date of first dose to the date of death. OS will be based on Kaplan-Meier estimates.	From the date of first dose to the date of death (up to 35 months)
Secondary	Part 1, Dose Optimization: Disease Control Rate (DCR)	DCR is defined as the percentage of participants with CR, PR, or stable disease (SD) (greater than or equal to [>=] 5 weeks from the first dose) by investigator per RECIST v1.1.	From the date of first dose until PD or death, whichever occurs first (up to 35 months)
Secondary	Part 1, Dose Optimization: Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants with CR, PR, or durable SD (duration of SD >=23 weeks) by investigator per RECIST v1.1.	From the date of first dose until PD or death, whichever occurs first (up to 35 months)
Secondary	Part 1, Dose Optimization: Time to Response (TTR)	TTR is defined as the time from the date of first dose to the day of the first documented CR or PR for confirmed responses by investigator per RECIST v1.1	From the date of first dose to the day of the first documented CR or PR (up to 35 months)
Secondary	Part 1, Dose Optimization, Cmax: Maximum Observed Concentration of BB-1701, Total Antibody and Eribulin (Payload)		Baseline up to 35 months
Secondary	Part 1, Dose Optimization, Tmax: Time to Reach Maximum Observed Concentration (Cmax) of BB-1701, Total Antibody and Eribulin (Payload)		Baseline up to 35 months
Secondary	Part 1, Dose Optimization, AUC(0-t): Area Under the Concentration-time Curve From Zero Time to Time of Last Quantifiable Concentration of BB-1701, Total Antibody and Eribulin (Payload)		Baseline up to 35 months
Secondary	Part 1, Dose Optimization, AUC(0-inf): Area Under the Concentration-time Curve From Zero Time to Infinity of BB-1701, Total Antibody and Eribulin (Payload)		Baseline up to 35 months
Secondary	Part 1, Dose Optimization, t1/2: Terminal Phase Elimination Half-life of BB-1701		Baseline up to 35 months
Secondary	Part 1, Dose Optimization, CL: Total Body Clearance of BB-1701		Baseline up to 35 months
Secondary	Part 1, Dose Optimization, Vss: Volume of Distribution at Steady State for BB-1701		Baseline up to 35 months
Secondary	Part 1, Dose Optimization, Ctrough: Trough Concentration of BB-1701		Baseline up to 35 months
Secondary	Part 1, Dose Optimization: Statistical Correlation Between Serum Concentrations of BB-1701 with ORR and AEs		Baseline up to 35 months
Secondary	Part 2, Dose Expansion: Duration of Response (DOR) Based on BICR Assessment by RECIST v1.1	DOR is defined as the time from the onset date of documented CR or PR for confirmed responses based on BICR by RECIST v1.1 to the date of PD or death, whichever occurs first.	From the date of documented CR or PR to the date of PD or death, whichever occurs first (up to 35 months)
Secondary	Part 2, Dose Expansion: Disease Control Rate (DCR) Based on BICR Assessment per RECIST v1.1	DCR is defined as the percentage of participants with CR, PR, or stable disease (SD) (>=5 weeks from the first dose) based on BICR per RECIST v1.1.	From the date of first dose until first documentation of CR or PR or SD (up to 35 months)
Secondary	Part 2, Dose Expansion: Time to Response (TTR) Based on BICR Assessment per RECIST v1.1	TTR is defined as the time from the date of first dose to the day of the first documented CR or PR for confirmed responses based on BICR per RECIST v1.1	From the date of first dose to the day of the first documented CR or PR (up to 35 months)
Secondary	Part 2, Dose Expansion: Clinical Benefit Rate (CBR) Based on BICR Assessment per RECIST v1.1	CBR is defined as the percentage of participants with CR, PR, or durable SD (duration of SD >=23 weeks) based on BICR per RECIST v1.1.	From the date of first dose until PD or death, whichever occurs first (up to 35 months)
Secondary	Part 2, Dose Expansion: Progression-free Survival (PFS) Based on BICR Assessment per RECIST v1.1	PFS is defined as the time from the date of first dose to the date of the first documentation of PD based on BICR per RECIST v1.1 or death, whichever occurs first.	From the date of first dose to the date of the first documentation of PD or death, whichever occurs first (up to 35 months)
Secondary	Part 2, Dose Expansion: Overall Survival (OS)	Overall survival (OS) is defined as the time from the date of first dose to the date of death. OS will be based on Kaplan-Meier estimates.	From the date of first dose to the date of death (up to 35 months)
Secondary	Part 2, Dose Expansion: Number of Participants With AEs	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product; Any new disease or exacerbation of an existing disease; any deterioration in non-protocol-required measurements of a laboratory value or other clinical test (example, ECG or x-ray) that results in symptoms, a change in treatment, or discontinuation of study drug; Recurrence of an intermittent medical condition (example, headache) not present pretreatment (baseline); An abnormal laboratory test result should be considered an AE if the identified laboratory abnormality leads to any type of intervention, withdrawal of study drug, or withholding of study drug, whether prescribed in the protocol or not. An AE does not necessarily have a causal relationship with the medicinal product.	Baseline up to 35 months
Secondary	Part 2, Dose Expansion: Number of Participants With Clinically Significant Laboratory Values	Clinical laboratory parameters includes hematology, chemistry, and urinalysis.	Baseline up to 35 months
Secondary	Part 2, Dose Expansion: Number of Participants With Clinically Significant Vital Sign Values	Vital sign parameters includes systolic and diastolic BP, pulse, respiratory rate, body temperature.	Baseline up to 35 months
Secondary	Part 2, Dose Expansion: Number of Participants With Clinically Significant 12-lead ECGs Values	Number of participants with clinically significant 12-lead ECGs values will be reported.	Baseline up to 35 months
Secondary	Part 2, Dose Expansion: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)	Number of participants with ECOG PS will be reported.	Baseline up to 35 months