Urothelial Carcinoma, Solid Tumor
Conditions
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.
Interventions
DRUGBL-B01D1
Administration by intravenous infusion
DRUGSI-B003
Administration by intravenous infusion
Sponsors
Sichuan Baili Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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. 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. 6. 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; 7. 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. 8. 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: 1. Blood routine: hemoglobin (HGB) ≥ 90g/L; Absolute neutrophil count (NEUT) ≥1.5×10 9 /L; Platelet count (PLT) ≥ 100×10 9 /L; 2. Renal function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥40 mL/min (according to Cockcroft and Gault formula). 3. Liver function: total bilirubin (TBIL≤1.5 ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were all ≤2.5 ULN, and AST and ALT were both ≤5.0 ULN when liver metastasis was present; 4. Coagulation function: international normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5ULN; 5. no severe cardiac dysfunction with left ventricular ejection fraction ≥50%; 9. Toxicity from previous antineoplastic therapy has returned to grade 1 or less as defined by NCI-CTCAE v5.0 (asymptomatic laboratory abnormalities such as ALP elevation, hyperuricemia, and hyperglycemia were considered by the investigator, and toxicity with no safety risk was judged by the investigator; Except for alopecia, grade 2 peripheral neurotoxicity, or decreased hemoglobin ≥90g/L). 10. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the start 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to approximately 24 months | The PFS is defined as the time from the first dose of medication to disease progression or death, whichever occurred first. |
| Disease control rate (DCR) | Up to approximately 24 months | The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]). |
| Duration of response (DOR) | Up to approximately 24 months | The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first. |
| Treatment-Emergent Adverse Event (TEAE) | Up to approximately 24 months | TEAE is defined as any adverse and unexpected change in body structure, function, or chemistry or any exacerbation of an existing condition (i.e., any clinically significant adverse change in frequency and/or intensity) during treatment. The type, frequency, and severity of TEAE will be assessed during treatment. |
Countries
China
Contacts
Primary ContactSa Xiao, PHD
Outcome results
None listed