Dose-randomized bulumtatug fuvedotin for triple-negative breast cancer previously treated with antibody-drug conjugates

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

This trial will test whether different doses of bulumtatug fuvedotin can help adults with recurrent or metastatic triple-negative breast cancer who have already received antibody-drug conjugates.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 52 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd. (Industry-sponsored)
• Drugs / interventions: enfortumab, tisotumab, radiation
• Locations: 6 sites (Duarte, California and 5 other locations)
• Trial ID: NCT06908928 on ClinicalTrials.gov

What this trial studies

This Phase 1, dose-randomization trial gives bulumtatug fuvedotin to adults with recurrent or metastatic triple-negative breast cancer who previously received an antibody-drug conjugate and a taxane. Eligible participants must have measurable disease by RECIST v1.1, ECOG 0-1, adequate organ function, and provide tumor tissue or biopsy. The study limits prior cytotoxic lines in the advanced setting and excludes patients previously treated with MMAE-based or nectin-4–targeting ADCs. Investigators will monitor safety, tolerability, and preliminary anti-tumor activity across dose cohorts at several U.S. cancer centers.

Who should consider this trial

Good fit: Adults (≥18) with recurrent or metastatic triple-negative breast cancer, measurable disease, ECOG 0-1, prior taxane and a topoisomerase-inhibitor–payload ADC, no more than three prior cytotoxic lines in the advanced setting, and adequate organ function are ideal candidates.

Not a fit: Patients who previously received MMAE-based or nectin-4–targeted ADCs, who have unstable central nervous system metastases, or who do not meet performance or organ-function criteria are unlikely to benefit from enrollment.

Why it matters

Potential benefit: If successful, this could provide a new treatment option for people with triple-negative breast cancer who progressed after prior ADC therapy.

How similar studies have performed: Other ADCs that deliver topoisomerase inhibitors, such as sacituzumab govitecan, have shown activity in TNBC, but bulumtatug fuvedotin represents a relatively new agent with limited clinical data to date.

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.

Where this trial is running

Duarte, California and 5 other locations

• City of Hope — Duarte, California, United States (Recruiting)
• UCSD Moores Cancer Center — La Jolla, California, United States (Recruiting)
• Anschutz Medical Center — Aurora, Colorado, United States (Recruiting)
• UChicago Medicine Comprehensive Cancer Center — Chicago, Illinois, United States (Recruiting)
• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Recruiting)

Study contacts

• Study coordinator: Fan Gao

Conditions Triple Negative Breast Cancer; 9MW2821; bulumtatug fuvedotin