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

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

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).

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: BB-1701

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Besançon, France
    • CHU Besancon - Hôpital Jean Minjoz
  • Montpellier, France
    • Institut Regional du Cancer de Montpellier
  • Plérin, France
    • Centre Armoricain de Radiotherapie Imagerie & Oncologie (CARIO)
  • Saint-Herblain, France
    • Institut de Cancerologie de Ouest (ICO) - Saint-Herblain
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan
      • Nagoya University Hospital
  • Hiroshima
    • Hiroshima, Hiroshima, Japan
      • Hiroshima City Hiroshima Citizens Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan
      • Hokkaido University Hospital
  • Hyōgo
    • Nishinomiya-shi, Hyōgo, Japan
      • Hyogo Medical University Hospital
  • Kagoshima-ken
    • Kagoshima, Kagoshima-ken, Japan
      • Sagara Hospital, Social Medical Corporation Hakuaikai
  • Kanagawa
    • Yokohama, Kanagawa, Japan
      • Kanagawa Cancer Center
  • Kyoto
    • Sakyo-ku, Kyoto, Japan
      • Kyoto University Hospital
  • Miyagi
    • Sendai, Miyagi, Japan
      • Tohoku University Hospital
  • Okayama-ken
    • Okayama, Okayama-ken, Japan
      • Okayama University Hospital
  • Saitama
    • Hidaka-shi, Saitama, Japan
      • Saitama Medical University International Medical Center
    • Kitaadachi-gun, Saitama, Japan
      • Saitama Cancer Center
  • Tokyo
    • Chuo-Ku, Tokyo, Japan
      • National Cancer Center Hospital (NCCH)
    • Chuou-ku, Tokyo, Japan
      • St. Luke's International Hospital
    • Koto Ku, Tokyo, Japan
      • The Cancer Institute Hospital of Japanese Foundation for Cancer Research
    • Shinagawa Ku, Tokyo, Japan
      • Showa Medical University
• Spain
  • Barcelona, Spain
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain
    • Hospital Beata Maria Ana
  • Madrid, Spain
    • HM Universitario Sanchinarro
• United States
  • California
    • Los Alamitos, California, United States, 90720
      • Cancer and Blood Specialty Clinic
    • Los Angeles, California, United States, 90095
      • UCLA Center for East-West Medicine
    • San Francisco, California, United States, 94143-2208
      • UCSF
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital
  • Florida
    • Orlando, Florida, United States, 32804
      • AdventHealth Cancer Institute - Orlando
    • Tampa, Florida, United States, 33612-9416
      • Moffitt Cancer Center
  • Indiana
    • Fort Wayne, Indiana, United States, 48604
      • Fort Wayne Medical Oncology & Hematology
    • Indianapolis, Indiana, United States, 46227
      • Community Cancer Center South
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Mission Blood and Cancer
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5000
      • University of Michigan Hospital
  • Missouri
    • St Louis, Missouri, United States, 63110-1032
      • Washington University in St. Louis School of Medicine
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • NHO Revive Research Institute LLC
    • Omaha, Nebraska, United States, 68130-2042
      • Nebraska Cancer Specialist
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Astera Cancer Care
    • Florham Park, New Jersey, United States, 07932-1049
      • Summit Medical Group
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • New Mexico Oncology Hematology Consultants
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195-0001
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic - Fairview Hospital - Cancer Center (Moll Cancer Center)
    • Cleveland, Ohio, United States, 44124
      • Cleveland Clinic - Hillcrest Hospital - Hillcrest Cancer Center
  • Oregon
    • Salem, Oregon, United States, 97301
      • Oregon Oncology Specialists
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213-3108
      • UPMC CancerCenter at Magee - Womens Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29607-5253
      • St. Francis Cancer Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
  • Tennessee
    • Germantown, Tennessee, United States, 38138-1762
      • The West Clinic, PLLC dba West Cancer Cente
  • Washington
    • Puyallup, Washington, United States, 98373-1428
      • Northwest Medical Specialties

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1, Dose Optimization, Cohort 1; HER2-positive or HER2-low, unresectable or metastatic BC.	Drug: BB-1701; BB-1701 will be administered as an intravenous infusion, every 3 weeks (21-day cycle).
Experimental: Part 1, Dose Optimization, Cohort 2; HER2-positive or HER2-low, unresectable or metastatic BC.	Drug: BB-1701; BB-1701 will be administered as an intravenous infusion, every 3 weeks (21-day cycle).
Experimental: Part 1, Dose Optimization, Cohort 3; HER2-positive or HER2-low, unresectable or metastatic BC.	Drug: BB-1701; BB-1701 will be administered as an intravenous infusion, every 3 weeks (21-day cycle).
Experimental: Part 2, Dose Expansion; HER2-positive or HER2-low, unresectable or metastatic BC.	Drug: BB-1701; BB-1701 will be administered as an intravenous infusion, every 3 weeks (21-day cycle).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
Part 1, Dose Optimization: Statistical Correlation Between Serum Concentrations of BB-1701 with ORR and AEs		Baseline up to 35 months
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)
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)
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)
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)
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)
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)
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
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
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
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
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
Part 1, Dose Optimization, Cmax: Maximum Observed Concentration of BB-1701, Total Antibody and Eribulin (Payload)		Baseline up to 35 months
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
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
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
Part 1, Dose Optimization, t1/2: Terminal Phase Elimination Half-life of BB-1701		Baseline up to 35 months
Part 1, Dose Optimization, CL: Total Body Clearance of BB-1701		Baseline up to 35 months
Part 1, Dose Optimization, Vss: Volume of Distribution at Steady State for BB-1701		Baseline up to 35 months
Part 1, Dose Optimization, Ctrough: Trough Concentration of BB-1701		Baseline up to 35 months

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Collaborators: Bliss Biopharmaceutical (Hangzhou) Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2024
• Primary Completion (Actual): March 18, 2026
• Study Completion (Actual): March 18, 2026

Study Registration Dates

• First Submitted: November 28, 2023
• First Submitted That Met QC Criteria: December 20, 2023
• First Posted (Actual): January 3, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Breast cancer; Breast carcinoma; Unresectable or metastatic breast cancer; HER2-positive or HER2-low unresectable or metastatic breast cancer; BB-1701
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: BB-1701-G000-205; 2023-506866-30 (Other Identifier: EU-CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No