Triple Negative Breast Cancer
Conditions
Keywords
9MW2821, bulumtatug fuvedotin
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.
Interventions
DRUGbulumtatug fuvedotin
given via intravenous infusion on day 1 and day 8 of every 21-day cycle at dose level 1
Sponsors
Mabwell (Shanghai) Bioscience Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Up to approximately 2 years | Objective Response Rate according to RECIST v1.1 by investigator assessment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate | Up to approximately 2 years | The percentage of patients who achieve complete response (CR), partial response (PR), or stable disease (SD) as per RECIST v1.1. |
| Clinical benefit rate | Up to approximately 2 years | The percentage of patients who achieve CR, PR, or SD for at least 6 months. |
| Duration of response | Up to approximately 2 years | The time from first documented response (CR or PR) to disease progression or death, whichever occurs first. |
| Progression-free survival | Up to approximately 2 years | The time from treatment initiation to disease progression or death from any cause. |
| Overall survival | Up to approximately 2 years | The time from treatment initiation to death from any cause. |
| Time to Maximum Concentration (Tmax) | Up to approximately 2 years | Time to reach the maximum observed concentration of bulumtatug fuvedotin, TAb, and MMAE in blood. |
| Maximum Concentration (Cmax) | Up to approximately 2 years | Maximum observed blood concentration of bulumtatug fuvedotin, TAb, and MMAE. |
| Half-life (t1/2) | Up to approximately 2 years | The time required for the blood concentration of bulumtatug fuvedotin, TAb, and MMAE to decrease by 50%. |
| Area Under the Plasma Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-t) | Up to approximately 2 years | The area under the plasma concentration-time curve from time zero to the last measurable concentration for bulumtatug fuvedotin, TAb, and MMAE. |
| Incidence, rate and severity of treatment-emergent adverse events. | Up to approximately 2 years | 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. |
| Immunogenicity | Up to approximately 2 years | Incidence and rates of ADA and Nab. |
Countries
United States
Contacts
CONTACTFan Gao
CONTACTWenhui Zhang, MD
Outcome results
None listed