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

Eisai

Status and phase: Enrolling; Phase 2

Conditions: Breast Cancer

Treatments: Drug: BB-1701

Study type: Interventional

Funder types: Industry

Identifiers

NCT06188559

2023-506866-30 (Other Identifier)

BB-1701-G000-205

Details and patient eligibility

About

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).

Enrollment: 135 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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135 participants in 4 patient groups

Part 1, Dose Optimization, Cohort 1

Experimental group

Description:

HER2-positive or HER2-low, unresectable or metastatic BC.

Treatment:

Drug: BB-1701

Part 1, Dose Optimization, Cohort 2

Experimental group

Description:

HER2-positive or HER2-low, unresectable or metastatic BC.

Treatment:

Drug: BB-1701

Part 1, Dose Optimization, Cohort 3

Experimental group

Description:

HER2-positive or HER2-low, unresectable or metastatic BC.

Treatment:

Drug: BB-1701

Part 2, Dose Expansion

Experimental group

Description:

HER2-positive or HER2-low, unresectable or metastatic BC.

Treatment:

Drug: BB-1701