A Study of BL-B01D1 + PD-1 in Patients With Locally Advanced or Metastatic Urothelial Carcinoma

A Phase II Clinical Study to Evaluate the Efficacy and Safety of BL-B01D1 + PD-1 Combination Therapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma

This study is a phase II clinical study to explore the efficacy and safety of BL-B01D1 + PD-1 combination therapy in patients with locally advanced or metastatic urothelial carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Urothelial Carcinoma
• Intervention / Treatment: Drug: BL-B01D1; Drug: PD-1

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sa Xiao, PHD; Phone Number: +8615013238943; Email: xiaosa@baili-pharm.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Dingwei Ye

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. All subjects voluntarily participated in the study and signed informed consent;
2. Male or female aged ≥18 years and ≤75 years;
3. Expected survival time ≥3 months;
4. ECOG 0-1;
5. Unresectable locally advanced or metastatic urothelial carcinoma confirmed by histopathology and/or cytology;
6. Participants should not have received previous systemic therapy for locally advanced or metastatic urothelial cancer;
7. A biopsy sample of archived tumor tissue or metastatic urothelial carcinoma must be available within 3 years for PD-L1 and other testing;
8. At least one measurable lesion meeting the RECIST v1.1 definition was required;
9. The level of organ function must meet the requirements on the premise that blood transfusion and the use of any cell growth factors and/or platelet-raising drugs are not allowed within 14 days before the first dose;
10. Previous treatment-related toxicity returned to ≤ grade 1 defined by NCI-CTCAE v5.0;
11. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the initiation of treatment, the serum or urine pregnancy test must be negative, and the patient must not be lactating; All enrolled patients should take adequate barrier contraception during the entire treatment cycle and for 6 months after the end of treatment.

Exclusion Criteria:

1. Prior ADC recipients with TOPI inhibitors as toxin;
2. Palliative radiotherapy within 2 weeks before the first dose;
3. Prior immunotherapy with grade ≥3 irAE or grade ≥2 immune-related myocarditis;
4. Use of an immunomodulatory drug within 14 days before the first dose of study drug;
5. The history of severe cardiovascular and cerebrovascular diseases in the past six months was screened;
6. QT prolongation, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
7. Active autoimmune and inflammatory diseases;
8. Receiving > before the first dose; Long-term systemic corticosteroid therapy with prednisone 10mg/d;
9. Other malignant tumors that progressed or required treatment within 5 years before the first dose;
10. Presence of: a) poorly controlled diabetes mellitus before starting study treatment; b) severe complications associated with diabetes mellitus; c) a glycated hemoglobin level of 8% or more; d) hypertension poorly controlled by two antihypertensive drugs; e) history of hypertensive crisis or hypertensive encephalopathy;
11. History of ILD, current ILD, or suspected ILD;
12. Complicated with pulmonary diseases leading to clinically severe respiratory impairment;
13. Screening for unstable thrombotic events requiring therapeutic intervention within the preceding 6 months; Infusion-related thrombosis was excluded;
14. Patients with active central nervous system metastases;
15. Patients with massive or symptomatic effusions or poorly controlled effusions;
16. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or allergic to any excipients of the test drug;
17. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
18. HIV antibody positive, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
19. Serious infection within 4 weeks before the first dose of study drug; Signs of pulmonary infection or active pulmonary inflammation within 4 weeks;
20. Participated in another clinical trial within 4 weeks before the first dose;
21. Patients with superior vena cava syndrome should not be rehydrated;
22. Have a history of psychotropic substance abuse with an inability to quit or a history of severe neurological or psychiatric illness;
23. Imaging examination showed that the tumor had invaded or wrapped the large thoracic vessels;
24. Severe unhealed wound, ulcer, or fracture within 4 weeks before signing the informed consent;
25. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
26. Subjects who are scheduled to receive live vaccine or receive live vaccine within 28 days before the first dose;
27. Other circumstances considered by the investigator to be inappropriate for participation in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BL-B01D1 + PD-1; Participants receive BL-B01D1 + PD-1 as intravenous infusion for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.	Drug: BL-B01D1; Administration by intravenous infusion for a cycle of 3 weeks.; Other Names: BMS-986507; iza-bren; izalontamab brengitecan; Drug: PD-1; Administration by intravenous infusion for a cycle of 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective response rate (ORR) is defined as the number of CR and PR in the treatment and control groups divided by the number of that group in the full analysis set (FAS).	Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum serum concentration (Cmax) of BL-B01D1 will be investigated.	Up to approximately 24 months
Disease Control Rate (DCR)	Disease Control Rate (DCR) : Percentage of all randomized subjects who rated the best overall response (BOR) as complete response (CR), partial response (PR), and disease stabilization (SD) according to RECIST 1.1 criteria.	Up to approximately 24 months
Duration of Response (DOR)	Duration of Response (DOR) : defined as the period from the date when tumor response is first recorded to the date when objective tumor progression is first recorded or the date of death.	Up to approximately 24 months
Treatment Emergent Adverse Event (TEAE)	TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-B01D1. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-B01D1.	Up to approximately 24 months
Anti-drug antibody (ADA)	Frequency of anti-BL-B01D1 antibody (ADA) will be investigated.	Up to approximately 24 months
Progression-free survival (PFS)	Progression-free survival (PFS) as assessed by BIRC is defined as the time between the date subjects are randomized and the first observation of disease progression (based on BICR's image-based assessment) or death.	Up to approximately 24 months
Tmax	Time to maximum serum concentration (Tmax) of BL-B01D1 will be investigated.	Up to approximately 24 months
Ctrough	Ctrough is defined as the lowest serum concentration of BL-B01D1 prior to the next dose will be administered.	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Collaborators: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Dingwei Ye, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: May 5, 2024
• First Submitted That Met QC Criteria: May 5, 2024
• First Posted (Actual): May 8, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2025
• Last Update Submitted That Met QC Criteria: May 5, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell
• Other Study ID Numbers: BL-B01D1-204-03

Drug and device information, study documents

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