An Open-Label, Multicenter Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SIM0237 Alone or in Combination with BCG in Non-Muscle-Invasive Bladder Cancer

Jiangsu Simcere Pharmaceutical Co., Ltd.14 sites in 1 country152 target enrollmentJanuary 23, 2024

ConditionsNon-Muscle-Invasive Bladder Cancer (NMIBC)

InterventionsSIM0237 SIM0237 and BCG

DrugsSIM0237 SIM0237 and BCG

Overview

Phase: Phase 1
Intervention: SIM0237
Conditions: Non-Muscle-Invasive Bladder Cancer (NMIBC)
Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Enrollment: 152
Locations: 14
Primary Endpoint: Dose escalation:Dose limited toxicity (DLT)
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open-label, multicenter phase 1 study to evaluate the safety, efficacy, and pharmacokinetics (PK) characteristics of SIM0237 alone or in combination with bacillus Calmette-Guerin (BCG) in participants with Non-Muscle-Invasive Bladder Cancer (NMIBC)

Detailed Description

The study starts with a dose escalation part followed by a dose expansion part. The primary objective of the dose escalation part is to evaluate the safety and tolerability of SIM0237 alone or in combination with BCG, and determine the recommended dose(s) (RD). The primary objective of the dose expansion part is to evaluate the preliminary efficacy of SIM0237 alone or in combination with BCG.

Registry

clinicaltrials.gov

Start Date

January 23, 2024

End Date

December 2030

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Jiangsu Simcere Pharmaceutical Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Written informed consent.
•≥ 18 years of age, male or female.
•• Histologically confirmed presence of BCG-unresponsive CIS (with or without Ta or T1 disease) or histologically confirmed presence of BCG-unresponsive high-grade Ta or T1 disease. Histologic confirmation of urothelial carcinoma (mixed histology tumors allowed if urothelial histology is predominant histology).
•Dose escalation phase: BCG-unresponsive high-risk NMIBC.
•Dose expansion phase: a) Cohorts 1 and 3: BCG-unresponsive CIS (with or without Ta or T1 disease); b) Cohort 2 and 4: BCG-unresponsive high-risk Ta or T1 disease.
•Absence of resectable disease after transurethral resection (TURBT) procedures \[residual carcinoma in situ (CIS) acceptable\]. patients with T1 tumors must undergo repeat resection and pathological test if initial pathological test sample did not include muscularis propria, to ensure the inclusive of muscularis propria and the absence of invasive tumor.
•Not suitable for or unwilling to undergo radical cystectomy.
•ECOG performance status of 0, 1or
•Life expectancy ≥ 2 years.
•Adequate hematologic and organ function.

Exclusion Criteria

•• Subjects received TURBT or other surgical treatment for bladder lesions or pelvic radiotherapy or interventional therapy within 2 weeks prior to the first dose.
•Previous treatment with: a) IL-15 or IL-2; b) immune checkpoint inhibitors (such as anti-PD-1 or PD-L1 antibodies), ADCs, chemotherapies, oncolytic viruses, BCG or other anti-tumor treatments, unless there is clear evidence of disease persistence/recurrence/progression after the above treatments and beyond 4 weeks prior to the first dose; c) Chinese herbal medicine treatment beyond 2 weeks prior to the first dose is allowed; d) A single immediate instillation of chemotherapy within 4 weeks prior to the first dose is allowed; e) intravesical instillation of mucosal protective agents (e.g., sodium hyaluronate) are allowed.
•Subject is participating in an investigational drug or investigational device study.
•Subjects have not recovered from AEs caused by previous anti-tumor treatment.
•History/evidence of prior muscle-invasive, locally advanced, metastatic bladder cancer or upper urinary tract (kidney, renal pelvis, ureter) and prostatic urethral tumors; or evidence of Ta/T1/CIS urothelial transitional cell carcinoma outside the bladder (urethra, ureter, renal pelvis) during the screening period.
•Patients with other malignancies within 5 years before the first dose.
•Any active infection or urinary tract infection requiring systemic treatment by intravenous infusion within 2 weeks before the first dose.
•Subjects with clinically significant cardiovascular disease within 6 months before the first dose of study treatment.
•Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS).
•Active or chronic hepatitis B or hepatitis C infection.