A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SIM0237 Alone or in Combination with BCG in NMIBC
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
1 other identifier
interventional
152
1 country
14
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)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2024
Longer than P75 for phase_1
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 7, 2023
CompletedFirst Posted
Study publicly available on registry
January 2, 2024
CompletedStudy Start
First participant enrolled
January 23, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2030
January 15, 2025
June 1, 2024
2.9 years
December 7, 2023
January 13, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Dose escalation:Dose limited toxicity (DLT)
DLT observation period (up to 21 days)
Dose escalation: Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Incidence and severity of adverse events (AEs) and serious adverse events(SAEs),and lab abnormalities
through study completion, an average of 5 years
Dose expansion:Complete response (CR) rate at Month 3
Complete response (CR) rate at of Cohort 1 and Cohort 3
through study completion, an average of 5 years
Dose escalation: Percentage of participants experiencing AE related dose interruptions and dose delays, dose intensity
Occurrence of AE related dose interruptions, dose delays and dose intensity
through study completion, an average of 5 years
Study Arms (6)
Dose escalation-mono
EXPERIMENTALBCG-unresponsive high-risk NMIBC, receiving SIM0237 monotherapy intravesically.
Dose escalation-combo
EXPERIMENTALBCG-unresponsive high-risk NMIBC, receiving SIM0237 and BCG intravesically.
Dose expansion-Cohort 1
EXPERIMENTALBCG-unresponsive CIS, receiving SIM0237 monotherapy intravesically.
Dose expansion-Cohort 3
EXPERIMENTALBCG-unresponsive CIS, receiving SIM0237 and BCG intravesically.
Dose expansion-Cohort 4
EXPERIMENTALBCG-unresponsive high-risk Ta or T1, receiving SIM0237 and BCG intravesically.
Dose expansion-Cohort 2
EXPERIMENTALBCG-unresponsive high-risk Ta or T1, receiving SIM0237 monotherapy intravesically.
Interventions
Several dose levels of SIM0237 will be administered as a single agent for evaluation
Several dose levels of SIM0237 will be administered in combination with a fixed dose of BCG for evaluation
Eligibility Criteria
You may qualify if:
- 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 2.
- Life expectancy ≥ 2 years.
- Adequate hematologic and organ function.
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test. WOCBP and male subjects agree to use adequate contraception.
- Tumor tissue (archival or fresh) for biomarker analysis.
You may not qualify if:
- 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.
- Known or suspected active autoimmune diseases.
- Concurrent use of any other anticancer therapy or chronic use of systemic corticosteroids at immunosuppressive doses (more than 10 mg/day prednisone or equivalent).
- History of pneumonitis or interstitial lung disease or severe obstructive pulmonary disease that requires oral or intravenous steroids to help recover.
- Known to be allergic or intolerant to study drugs, monoclonal antibodies, excipients; or allergic or intolerant to BCG (only for subjects receiving combined BCG therapy)
- Subjects discontinued prior BCG treatment due to AEs such as toxemia, systemic infection, or urinary incontinence (only for subjects receiving combined BCG therapy).
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
Peking University Third Hospital
Beijing, Beijing Municipality, 100191, China
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060, China
Harbin Medical University Cancer Hospital
Haerbin, Heilongjiang, 150000, China
Henan Cancer Hospital Affiliated Cancer Hospital of Zhengzhou University
Zhengzhou, Henan, 450003, China
Renmin Hospital of Wuhan University
Wuhan, Hubei, 430060, China
Hunan Cancer Hospital
Changsha, Hunan, 410031, China
Qilu Hospital of Shandong University
Jinan, Shandong, 250012, China
The Affiliated Hospital of Qingdao University
Qingdao, Shandong, 266071, China
Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200092, China
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 201321, China
First Hospital of Shanxi Medcial University
Taiyuan, Shanxi, 30012, China
West China Hospital of Sichuan University
Chengdu, Sichuan, 610041, China
The Second Hospital of Tianjin Medical University
Tianjin, Tianjin Municipality, 300211, China
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325015, China
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 7, 2023
First Posted
January 2, 2024
Study Start
January 23, 2024
Primary Completion (Estimated)
January 1, 2027
Study Completion (Estimated)
December 1, 2030
Last Updated
January 15, 2025
Record last verified: 2024-06
Data Sharing
- IPD Sharing
- Will not share