Clinical trial NCT06908928: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Triple Negative Breast Cancer
Keywords: 9MW2821
bulumtatug fuvedotin
Lead sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-04-03
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: Objective Response Rate
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Disease control rate
timeFrame: Up to approximately 2 years
measure: Clinical benefit rate
timeFrame: Up to approximately 2 years
measure: Duration of response
timeFrame: Up to approximately 2 years
measure: Progression-free survival
timeFrame: Up to approximately 2 years
measure: Overall survival
timeFrame: Up to approximately 2 years
measure: Time to Maximum Concentration (Tmax)
timeFrame: Up to approximately 2 years
measure: Maximum Concentration (Cmax)
timeFrame: Up to approximately 2 years
measure: Half-life (t1/2)
timeFrame: Up to approximately 2 years
measure: Area Under the Plasma Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-t)
timeFrame: Up to approximately 2 years
measure: Incidence, rate and severity of treatment-emergent adverse events.
timeFrame: Up to approximately 2 years
measure: Immunogenicity
timeFrame: Up to approximately 2 years
measure: Immunogenicity
timeFrame: Up to approximately 2 years
Other outcomes:
measure: Efficacy parameters and biomarkers including but not limited to nectin-4 expression level.
timeFrame: Up to approximately 2 years
Locations:
Study officials:
References: