Phase 2 Study of BB-1701 in HER2 positive or HER2-low metastatic breast cancer

Prior treatment

• Presence of brain or subdural metastases, unless subject 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.
• 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 (eg, 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.

Other illness

• Known history of active bacillus tuberculosis (TB).
• Any medical or other condition which, in the opinion of the investigator, would preclude the subject’s participation in the clinical study.

Lab values

• 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 CD4+ T-cell (CD4+) count ≥350 cells/μL and an HIV viral load less than 400 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.
• Any of the following cardiac conditions: - Congestive heart failure greater than New York Heart Association Class II or left ventricular ejection fraction (LVEF) <50% measured by multigated acquisition (MUGA) scan or echocardiogram. - Has a corrected QT interval prolongation per Fridericia formula (QTcF) >470 ms (for both males and females) based on screening triplicate 12-lead ECG.

Other

• Diagnosed with meningeal carcinomatosis.

• Subject must be willing and able to comply with all aspects of the protocol and as such provide written informed consent prior to any study-specific screening procedures.
• Life expectancy of at least 3 months.
• Adequate organ function and laboratory parameters.
• 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 T-DXd treatment.
• Must have previously received T-DXd.
• Sufficient tumor tissue is required for HER2 status testing at a central laboratory.
• Measurable disease meeting the following criteria as assessed by the investigator:according to RECIST 1.1. NOTE: Subjects 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 regimens 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.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.