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

Official title

An Open-Label, Multicenter, Phase Ib Dose Randomization Study of Bulumtatug Furvedotin (BFv; 9MW2821) in Subjects With Recurrent or Metastatic Triple-Negative Breast Cancer Previously Treated With Antibody-Drug Conjugates

Overview

The goal of this clinical trial is to investigate if treatment with bulumtatug fuvedotin is effective in triple-negative breast cancer patients who have previously received treatment with an antibody-drug conjugates.

Interventions

• Drug bulumtatug fuvedotin
  given via intravenous infusion on day 1 and day 8 of every 21-day cycle at dose level 1
• Drug bulumtatug fuvedotin
  given via intravenous infusion on day 1 and day 8 of every 21-day cycle at dose level 2

Primary outcome measures

• Objective Response Rate [Time frame: Up to approximately 2 years]

Secondary outcome measures (12)

• Disease control rate [Time frame: Up to approximately 2 years]
• Clinical benefit rate [Time frame: Up to approximately 2 years]
• Duration of response [Time frame: Up to approximately 2 years]
• Progression-free survival [Time frame: Up to approximately 2 years]
• Overall survival [Time frame: Up to approximately 2 years]
• Time to Maximum Concentration (Tmax) [Time frame: Up to approximately 2 years]
• Maximum Concentration (Cmax) [Time frame: Up to approximately 2 years]
• Half-life (t1/2) [Time frame: Up to approximately 2 years]
• Area Under the Plasma Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-t) [Time frame: Up to approximately 2 years]
• Incidence, rate and severity of treatment-emergent adverse events. [Time frame: Up to approximately 2 years]
• Immunogenicity [Time frame: Up to approximately 2 years]
• Immunogenicity [Time frame: Up to approximately 2 years]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• Have received any prior treatment with enfortumab vedotin, tisotumab vedotin or other MMAE based or nectin-4 targeted antibody-drug conjugates.
• Unstable CNS metastasis requiring treatment in the last 28 days.
• Acute infection requiring IV treatment in the last 14 days.
• Grade ≥2 peripheral neuropathy.
• Pregnant or breastfeeding women.
• Life-threatening illness or uncontrolled medical conditions that could compromise the subject's safety or put the study outcomes at risk
• Any systemic anticancer therapy in the last 28 days prior to first administration of study drug.
• 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.
• Have received any strong CYP3A4 inhibitors within 14 days prior to the first dose of study drug.
• Subjects known to be hypersensitive to bulumtatug fuvedotin or to any components of the formulation.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 6 centers

• City of Hope — Duarte
• UCSD Moores Cancer Center — La Jolla
• Anschutz Medical Center — Aurora
• UChicago Medicine Comprehensive Cancer Center — Chicago
• Massachusetts General Hospital — Boston
• Memorial Sloan Kettering Cancer Center — New York

Identifiers

NCT: NCT06908928 · 9MW2821-2022-CP103

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗