A Phase II Clinical Study to Evaluate the Efficacy and Safety of SI-B003 Monotherapy and BL-B01D1+SI-B003 Combination Therapy (BL-B01D1+SI-B003) in Patients With Locally Advanced or Metastatic Urothelial Carcinoma and Other Solid Tumors

Sichuan Baili Pharmaceutical Co., Ltd.1 site in 1 country52 target enrollmentDecember 11, 2023

ConditionsUrothelial Carcinoma Solid Tumor

InterventionsBL-B01D1 SI-B003

Overview

Phase: Phase 2
Intervention: BL-B01D1
Conditions: Urothelial Carcinoma
Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Enrollment: 52
Locations: 1
Primary Endpoint: Objective response rate (ORR)
Status: Recruiting
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This phase II study is designed to explore the efficacy and safety of SI-B003 monotherapy and BL-B01D1+SI-B003 combination therapy in patients with locally advanced or metastatic urothelial carcinoma and other solid tumors.

Registry

clinicaltrials.gov

Start Date

December 11, 2023

End Date

December 1, 2027

Last Updated

7 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Sichuan Baili Pharmaceutical Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•All subjects voluntarily participated in the study and signed informed consent;
•Male or female aged ≥18 years and ≤75 years;
•Expected survival time ≥3 months;
•Locally advanced or metastatic urothelial carcinoma and other solid tumors confirmed by histopathology and/or cytology who have failed or cannot tolerate standard treatment or who currently have no standard treatment or cannot obtain standard treatment; (including but not limited to urothelial cancer, prostate cancer, kidney cancer) : ① Urothelial cancer should have received previous failure or intolerance to standard platinum-based chemotherapy; ② Prostate cancer with pathological type of adenocarcinoma should have received at least one previous novel hormonal therapy (abiraterone acetate, enzalutamide, etc.) and at least one failed or intolerant taxane regimen (docetaxel, cabazitaxel); ③ Clear cell renal cell carcinoma required previous failure or intolerance to standard first-line tyrosine kinase inhibitor (TKI) regimens. ④ Locally advanced or metastatic other urological malignancies (non-clear cell renal cancer, penile cancer, etc.) that failed standard treatment and were not suitable for surgery or radiotherapy. Treatment failure was defined as disease progression during or after treatment with systemic antitumor regimens. Intolerance refers to patients who have received standard treatment and have grade 3-4 adverse reactions, and refuse to continue the original regimen.
•Note: Recurrence or disease progression within 6 months of the last chemotherapy in multimodal therapy was considered as first-line treatment.
•Consent to provide archival tumor tissue specimens (10 unstained sections (anti-slip) surgical specimens (thickness 4-5μm)) or fresh tissue samples from primary or metastatic lesions within 3 years. If participants cannot provide tumor tissue samples, they can be enrolled if they meet other inclusion and exclusion criteria, after the evaluation of the investigator;
•Must have at least one measurable lesion according to RECIST v1.1 definition; Lesions that had been previously treated with radiation could be included in a measurable lesion only if there was definite disease progression after radiation therapy.
•Provided that no blood transfusions and no use of any cell growth factors and/or platelet-raising agents are allowed for 14 days prior to the screening period, organ function levels must meet the following criteria:
•Blood routine: hemoglobin (HGB) ≥ 90g/L; Absolute neutrophil count (NEUT) ≥1.5×10 9 /L; Platelet count (PLT) ≥ 100×10 9 /L;
•Renal function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥40 mL/min (according to Cockcroft and Gault formula).

Exclusion Criteria

•Previous use of an ADC drug with a topoisomerase I inhibitor as a toxin;
•Administration of chemotherapy or chemotherapy within 4 weeks or 5 half-lives, whichever is shorter, before the first dose Physical therapy, immunotherapy, definitive radiotherapy, major surgery (investigator's definition), targeted therapy (including Small molecule tyrosine kinase inhibitors) and other anti-tumor therapy; Mitomycin and nitrosoureas were given for the first time Within 6 weeks before treatment; Oral fluorouracil drugs such as S-1, capecitabine, or palliative radiotherapy for Within 2 weeks before the first dose; No exposure to wide-field radiotherapy within 4 weeks before study treatment for prostate cancer (tired) And ≥30% bone marrow), samarium must be completed 4 weeks prior to the first dose of treatment, and strontium and Lu 177 treatment This must be completed at least 12 weeks before the first administration of treatment, and radium-233 must precede the first administration of treatment At least 6 weeks to complete. Prostate cancer bone metastasis therapy such as bisphosphonates or denosumab should be administered before the first dose It was initiated at 4 weeks and was administered at a stable dose.
•Patients with a history of immunotherapy and grade ≥3 irAE or grade ≥2 immune-related myocarditis must be excluded;
•Use of immunomodulatory drugs within 14 days before the first use of the study drug, including but not limited to thymosin, Interleukin-2, interferon, etc. must be excluded;
•A history of severe cardiovascular and cerebrovascular diseases, including but not limited to:
•severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias or grade III atria requiring clinical intervention Ventricular block;
•prolonged QT interval at rest (QTc \> 450 msec in men or QTc \> 470 msec in women);
•cerebrovascular accident or transient ischemic attack within 6 months before the first dose; Symptomatic congestive History of heart failure (CHF) ≥ grade 2 (CTCAE 5.0) and New York Heart Association (NYHA) ≥ Grade 2 heart failure, transmural myocardial infarction history, unstable angina, etc.
•Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, requiring systemic treatment Psoriasis, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, etc., excluding type I sugar Urinary disorders, hypothyroidism that can be controlled with replacement therapy alone, skin disorders that do not require systemic treatment (e.g Vitiligo and psoriasis).
•Systemic corticosteroids (\> 10mg/ day prednisone, or equivalent) are required within 2 weeks before the study dose Doses of other corticosteroids) or immunosuppressive agents; Inhaled or topical administration of hormones, or due to adrenal The exception is those who were treated with physiological replacement doses of hormone for insufficiency;

Arms & Interventions

BL-B01D1 + SI-B003

Participants receive SI-B003 or BL-B01D1+SI-B003 dual therapy in the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. Administration will be discontinued because of disease progression or intolerable toxicity or for other reasons.

Intervention: BL-B01D1

BL-B01D1 + SI-B003

Intervention: SI-B003

Outcomes

Primary Outcomes

Objective response rate (ORR)

Time Frame: Up to approximately 24 months

ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.

Recommended Phase II Dose (RP2D)

Time Frame: Up to approximately 24 months

The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of SI-B003.