Clinical trial NCT06188559: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Breast cancer
Breast carcinoma
Unresectable or metastatic breast cancer
HER2-positive or HER2-low unresectable or metastatic breast cancer
BB-1701
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Bliss Biopharmaceutical (Hangzhou) Co., Ltd
First posted: 2024-01-03
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: For Dose Optimization (Part 1), this study is randomized and for Dose Expansion (Part 2), there will be no randomization.
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1, Dose Optimization: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline up to 35 months
measure: Part 1, Dose Optimization: Number of Participants With Clinically Significant Laboratory Values
timeFrame: Baseline up to 35 months
measure: Part 1, Dose Optimization: Number of Participants With Clinically Significant Vital Sign Values
timeFrame: Baseline up to 35 months
measure: Part 1, Dose Optimization: Number of Participants With Clinically Significant 12-lead ECGs Values
timeFrame: Baseline up to 35 months
measure: Part 1, Dose Optimization: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
timeFrame: Baseline up to 35 months
measure: Part 1, Dose Optimization: Objective Response Rate (ORR)
timeFrame: From date of first dose of study drug until first documentation of CR or PR (up to 35 months)
measure: Part 2, Dose Expansion: Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Assessment per RECIST v1.1
timeFrame: From date of first dose of study drug until first documentation of CR or PR (up to 35 months)
Secondary outcomes:
measure: Part 1, Dose Optimization: Duration of Response (DOR)
timeFrame: From the date of documented CR or PR to the date of PD or death, whichever occurs first (up to 35 months)
measure: Part 1, Dose Optimization: Progression-free Survival (PFS)
timeFrame: From the date of first dose to the date of the first documentation of PD or death, whichever occurs first (up to 35 months)
measure: Part 1, Dose Optimization: Overall Survival (OS)
timeFrame: From the date of first dose to the date of death (up to 35 months)
measure: Part 1, Dose Optimization: Disease Control Rate (DCR)
timeFrame: From the date of first dose until PD or death, whichever occurs first (up to 35 months)
measure: Part 1, Dose Optimization: Clinical Benefit Rate (CBR)
timeFrame: From the date of first dose until PD or death, whichever occurs first (up to 35 months)
measure: Part 1, Dose Optimization: Time to Response (TTR)
timeFrame: From the date of first dose to the day of the first documented CR or PR (up to 35 months)
measure: Part 1, Dose Optimization, Cmax: Maximum Observed Concentration of BB-1701, Total Antibody and Eribulin (Payload)
timeFrame: Baseline up to 35 months
measure: Part 1, Dose Optimization, Tmax: Time to Reach Maximum Observed Concentration (Cmax) of BB-1701, Total Antibody and Eribulin (Payload)
timeFrame: Baseline up to 35 months
measure: 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)
timeFrame: Baseline up to 35 months
measure: 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)
timeFrame: Baseline up to 35 months
measure: Part 1, Dose Optimization, t1/2: Terminal Phase Elimination Half-life of BB-1701
timeFrame: Baseline up to 35 months
measure: Part 1, Dose Optimization, CL: Total Body Clearance of BB-1701
timeFrame: Baseline up to 35 months
measure: Part 1, Dose Optimization, Vss: Volume of Distribution at Steady State for BB-1701
timeFrame: Baseline up to 35 months
measure: Part 1, Dose Optimization, Ctrough: Trough Concentration of BB-1701
timeFrame: Baseline up to 35 months
measure: Part 1, Dose Optimization: Statistical Correlation Between Serum Concentrations of BB-1701 with ORR and AEs
timeFrame: Baseline up to 35 months
measure: Part 2, Dose Expansion: Duration of Response (DOR) Based on BICR Assessment by RECIST v1.1
timeFrame: From the date of documented CR or PR to the date of PD or death, whichever occurs first (up to 35 months)
measure: Part 2, Dose Expansion: Disease Control Rate (DCR) Based on BICR Assessment per RECIST v1.1
timeFrame: From the date of first dose until first documentation of CR or PR or SD (up to 35 months)
measure: Part 2, Dose Expansion: Time to Response (TTR) Based on BICR Assessment per RECIST v1.1
timeFrame: From the date of first dose to the day of the first documented CR or PR (up to 35 months)
measure: Part 2, Dose Expansion: Clinical Benefit Rate (CBR) Based on BICR Assessment per RECIST v1.1
timeFrame: From the date of first dose until PD or death, whichever occurs first (up to 35 months)
measure: Part 2, Dose Expansion: Progression-free Survival (PFS) Based on BICR Assessment per RECIST v1.1
timeFrame: From the date of first dose to the date of the first documentation of PD or death, whichever occurs first (up to 35 months)
measure: Part 2, Dose Expansion: Overall Survival (OS)
timeFrame: From the date of first dose to the date of death (up to 35 months)
measure: Part 2, Dose Expansion: Number of Participants With AEs
timeFrame: Baseline up to 35 months
measure: Part 2, Dose Expansion: Number of Participants With Clinically Significant Laboratory Values
timeFrame: Baseline up to 35 months
measure: Part 2, Dose Expansion: Number of Participants With Clinically Significant Vital Sign Values
timeFrame: Baseline up to 35 months
measure: Part 2, Dose Expansion: Number of Participants With Clinically Significant 12-lead ECGs Values
timeFrame: Baseline up to 35 months
measure: Part 2, Dose Expansion: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
timeFrame: Baseline up to 35 months
Other outcomes:
Locations:
city: Los Alamitos
country: United States
facility: Cancer and Blood Specialty Clinic
state: California
city: Los Angeles
country: United States
facility: UCLA Center for East-West Medicine
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Orlando
country: United States
facility: AdventHealth Cancer Institute - Orlando
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology & Hematology
state: Indiana
city: Indianapolis
country: United States
facility: Community Cancer Center South
state: Indiana
city: Des Moines
country: United States
facility: Mission Blood and Cancer
state: Iowa
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University in St. Louis School of Medicine
state: Missouri
city: Lincoln
country: United States
facility: NHO Revive Research Institute LLC
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Cancer Specialist
state: Nebraska
city: East Brunswick
country: United States
facility: Astera Cancer Care
state: New Jersey
city: Florham Park
country: United States
facility: Summit Medical Group
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Oncology Hematology Consultants
state: New Mexico
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic - Fairview Hospital - Cancer Center (Moll Cancer Center)
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic - Hillcrest Hospital - Hillcrest Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Salem
country: United States
facility: Oregon Oncology Specialists
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC CancerCenter at Magee - Womens Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: St. Francis Cancer Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Germantown
country: United States
facility: The West Clinic, PLLC dba West Cancer Cente
state: Tennessee
city: Puyallup
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Besancon
country: France
facility: CHU Besançon - Hôpital Jean Minjoz
city: Montpellier
country: France
facility: Institut Régional du Cancer de Montpellier
city: Plerin
country: France
facility: Centre Armoricain de Radiotherapie Imagerie & Oncologie (CARIO)
city: Saint-Herblain Cedex
country: France
facility: Institut de Cancerologie de Ouest (ICO) - Saint-Herblain
city: Nagoya Shi
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Hiroshima-shi
country: Japan
facility: Hiroshima City Hiroshima Citizens Hospital
state: Hiroshima-ken
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Nishinomiya-shi
country: Japan
facility: Hyogo Medical University Hospital
state: Hyogo-Ken
city: Kagoshima Shi
country: Japan
facility: Sagara Hospital, Social Medical Corporation Hakuaikai
state: Kagoshima
city: Yokohama Shi
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Chuo-Ku
country: Japan
facility: National Cancer Center Hospital (NCCH)
state: Kansai
city: Sakyo-ku
country: Japan
facility: Kyoto University Hospital
state: Kyoto
city: Sendai Shi
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Okayama Shi
country: Japan
facility: Okayama University Hospital
state: Okayama
city: Hidaka-shi
country: Japan
facility: Saitama Medical University International Medical Center
state: Saitama-ken
city: Kitaadachi-gun
country: Japan
facility: Saitama Cancer Center
state: Saitama
city: Chuou-ku
country: Japan
facility: St. Luke's International Hospital
state: Tokyo
city: Koto Ku
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation for Cancer Research
state: Tokyo
city: Shinagawa Ku
country: Japan
facility: Showa University
state: Tokyo
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: HM Universitario Sanchinarro
city: Madrid
country: Spain
facility: Hospital Beata María Ana
Study officials:
References: