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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Triple Negative Breast Cancer
• Intervention / Treatment: Drug: bulumtatug fuvedotin; Drug: bulumtatug fuvedotin

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Fan Gao; Phone Number: +8615122736763; Email: fan.gao@mabwell.com
• Study Contact Backup: Name: Wenhui Zhang, MD; Email: wenhui.zhang@mabwell.com

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
      • Principal Investigator: Hope Rugo
      • Contact: Phone Number: 877-460-2954
    • La Jolla, California, United States, 92093
      • Recruiting
      • UCSD Moores Cancer Center
      • Principal Investigator: Rebecca Shatsky
      • Contact: Phone Number: 866-773-2703
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Anschutz Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • UChicago Medicine Comprehensive Cancer Center
      • Principal Investigator: Rita Nanda
      • Contact: Phone Number: 855-702-8222
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10021
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Principal Investigator: Nour Abuhadra
      • Contact: Phone Number: 646-888-6885

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose level 1 of BFv	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
Experimental: Dose level 2 of BFv	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective Response Rate according to RECIST v1.1 by investigator assessment	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate	The percentage of patients who achieve complete response (CR), partial response (PR), or stable disease (SD) as per RECIST v1.1.	Up to approximately 2 years
Clinical benefit rate	The percentage of patients who achieve CR, PR, or SD for at least 6 months.	Up to approximately 2 years
Duration of response	The time from first documented response (CR or PR) to disease progression or death, whichever occurs first.	Up to approximately 2 years
Progression-free survival	The time from treatment initiation to disease progression or death from any cause.	Up to approximately 2 years
Overall survival	The time from treatment initiation to death from any cause.	Up to approximately 2 years
Time to Maximum Concentration (Tmax)	Time to reach the maximum observed concentration of bulumtatug fuvedotin, TAb, and MMAE in blood.	Up to approximately 2 years
Maximum Concentration (Cmax)	Maximum observed blood concentration of bulumtatug fuvedotin, TAb, and MMAE.	Up to approximately 2 years
Half-life (t1/2)	The time required for the blood concentration of bulumtatug fuvedotin, TAb, and MMAE to decrease by 50%.	Up to approximately 2 years
Area Under the Plasma Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-t)	The area under the plasma concentration-time curve from time zero to the last measurable concentration for bulumtatug fuvedotin, TAb, and MMAE.	Up to approximately 2 years
Incidence, rate and severity of treatment-emergent adverse events.	Incidence, rate and severity of AE, SAE, TRAE and AESI. Frequency of clinically significant abnormalities in physical examination, safety laboratory tests, urinalysis, vital signs, and 12-Lead ECG record. Safety will be reported as incidence and rate of treatment-emergent adverse events using NCI CTCAE v5.0 criteria.	Up to approximately 2 years
Immunogenicity	Incidence and rates of ADA and Nab.	Up to approximately 2 years
Immunogenicity	Titre of ADA and Nab.	Up to approximately 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy parameters and biomarkers including but not limited to nectin-4 expression level.	The proportion of nectin-4 positive and negative patients. The proportion of nectin-4 positive patients who experienced objective response. The proportion of nectin-4 negative patients who experienced objective response.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: March 20, 2025
• First Submitted That Met QC Criteria: March 26, 2025
• First Posted (Actual): April 3, 2025

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: 9MW2821; bulumtatug fuvedotin
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Skin and Connective Tissue Diseases; Triple Negative Breast Neoplasms
• Other Study ID Numbers: 9MW2821-2022-CP103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No