NCT07869836PHASE3Recruiting
BL-M07D1 (Trastuzumab Brengitecan T-bren) vs Standard of Care Platinum-based Chemotherapy (PBC) for HER2-expressing Metastatic Urothelial Cancer After Progression on Anti-PD-(L)1-based Therapy
SystImmune Inc.
Start Date
9/1/2026
Completion Date
12/1/2029
Summary
The objective of the study is to evaluate the efficacy and safety of T-bren in participants with HER2 expressing metastatic UC with progression on or after anti-PD-(L)1-based therapy.
Detailed Description
This study is a Global Phase 3, randomized, open-label, multicenter study of T-bren for the treatment of metastatic UC. This study will assess the efficacy and safety of T-bren versus PBC in adult participants with HER2-expressing UC after progression on anti-PD-(L)1-based therapy.
Eligibility Criteria
Age Range: 18 years to No maximum
Inclusion Criteria:
* Histologically or cytologically documented metastatic or surgically unresectable transitional cell carcinoma (TCC) of the urothelium involving the renal pelvis, ureter, bladder, or urethra. Minor histologic variants (ie, \<50% overall) are acceptable, provided that TCC is the dominant histology.
* Disease progression or recurrence during or following anti-PD-(L)1-based therapy.
* Fresh biopsy or archival tumor samples.
* Documented HER2 expression by central laboratory testing.
* Eligible to receive carboplatin or cisplatin in combination with gemcitabine.
* At least 1 measurable lesion based on RECIST v1.1.
* An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1.
* Adequate organ function.
* Adequate coagulation parameters.
Exclusion Criteria:
* Prior topoisomerase inhibitor-based ADC therapy.
* Primary tumors in the central nervous system (CNS), active or untreated CNS metastases, or carcinomatous meningitis.
* Bladder cancers with small cell histology.
* Other prior or concurrent malignancies except for certain localized cancers or low-grade prostate cancer (if approved by sponsor), or other malignancy treated with curative intent with a disease-free interval of at least 3 years.
* Prior history of clinically significant bleeding, or perforation of the gastrointestinal tract within 6 months of randomization.
* Active autoimmune diseases and inflammatory diseases.
* History of noninfectious interstitial lung disease (ILD)/pneumonitis that required treatment with steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
* Advanced/clinically significant lung disease (eg, poorly controlled chronic obstructive pulmonary disease or asthma, restrictive lung disease, or pulmonary hypertension) within 6 months prior to randomization.
* Known human immunodeficiency virus infection.
* Active hepatitis B virus (HBV) infection.
* Active hepatitis C virus (HCV) infection.
* Active or latent tuberculosis.
* Other protocol-specified inclusion/ exclusion criteria apply
Interventions
DRUG
T-Bren, Dose level 1
DRUG
T-bren, Dose level 2
DRUG
Gemcitabine + Platinum Based Chemotherapy (Cisplatin or Carboplatin)
Conditions
Urothelial CancerMetastatic Urothelial CancerBladder CancerBladder Cancer (BC)Bladder (Urothelial, Transitional Cell) CancerBladder (Urothelial, Transitional Cell) Cancer Metastatic or UnresectableBladder CaBladder Cancer RecurrentBladder Cancer Stage IVUrothelial Carcinoma BladderUrothelial Carcinoma RecurrentUrothelial Carcinoma of the Urinary Bladder
Locations
Central Georgia Cancer Center
Macon, Georgia 31210
United States
Central Georgia Cancer Center
Macon, Georgia 31210
United States