A Dose Randomization Study of Bulumtatug Fuvedotin in TNBC Patients Previously Treated With ADCs

Prior treatment

• Have received any prior treatment with enfortumab vedotin, tisotumab vedotin or other MMAE based or nectin-4 targeted antibody-drug conjugates.
• Any systemic anticancer therapy in the last 28 days prior to first administration of study drug.
• Have received any strong CYP3A4 inhibitors within 14 days prior to the first dose of study drug.
• History of drug abuse including narcotic and psychiatric drugs within 12 months prior to screening.
• Have received a live vaccine within 30 days of planned start of study therapy.

Other illness

• Acute infection requiring IV treatment in the last 14 days.
• Life-threatening illness or uncontrolled medical conditions that could compromise the subject's safety or put the study outcomes at risk
• Active HCV, HBV or HIV infection unless well controlled with anti-viral therapy.
• Active or chronic corneal disorder, keratitis, corneal ulcerations or Sjogren's syndrome.
• Have any ongoing acute inflammatory skin disease or chronic skin disease not well controlled.
• Have been diagnosed with another primary malignancy except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or subjects with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
• Have significant, uncontrolled or active cardiovascular disease
• Have active or a history of pneumonitis or interstitial lung disease that requires corticosteroid treatment. Patients with radiation pneumonitis that does not require treatment is allowed.
• Have uncontrolled diabetes.

Other

• Unstable CNS metastasis requiring treatment in the last 28 days.
• Grade ≥2 peripheral neuropathy.
• Pregnant or breastfeeding women.
• Subjects known to be hypersensitive to bulumtatug fuvedotin or to any components of the formulation.

• Patient has measurable disease by RECIST v1.1
• Recurrent or metastatic triple-negative breast cancer patients as per current ASCO/CAP guidelines
• Patient has received prior treatment with a taxane and an antibody-drug conjugate with a topoisomerase inhibitor payload.
• Patient has received no more than 3 prior lines of cytotoxic therapy in the locally advanced or metastatic setting.
• Provision of archival tumor tissue or fresh tumor biopsy.
• Capable of giving informed consent
• Male or female subjects aged ≥ 18 years.
• Subjects must be willing to receive blood transfusions if medically indicated.
• ECOG 0-1
• Adequate hematologic and organ function
• Life expectancy of at least 3 months as assessed by the investigator
• Compliance with contraceptive requirement