Investigating SIM0237 for treating Non-Muscle-Invasive Bladder Cancer

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

This study is testing a new treatment called SIM0237 for people with Non-Muscle-Invasive Bladder Cancer who haven't responded to standard therapy, to see if it is safe and effective.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 152 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 14 sites (Beijing, Beijing Municipality and 13 other locations)
• Trial ID: NCT06186414 on ClinicalTrials.gov

What this trial studies

This open-label, multicenter phase 1 study evaluates the safety, tolerability, pharmacokinetics, and preliminary efficacy of SIM0237, both alone and in combination with bacillus Calmette-Guerin (BCG), in patients with Non-Muscle-Invasive Bladder Cancer (NMIBC). The study consists of a dose escalation phase to determine the recommended doses and a dose expansion phase to assess the preliminary efficacy of the treatment. Participants must have histologically confirmed BCG-unresponsive NMIBC. The study aims to provide insights into the potential of SIM0237 as a new treatment option for this condition.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed BCG-unresponsive NMIBC.

Not a fit: Patients with resectable disease or those who do not meet the specific histological criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with BCG-unresponsive NMIBC.

How similar studies have performed: While there have been studies on BCG and other treatments for NMIBC, the specific combination of SIM0237 with BCG is novel and has not been extensively tested.

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 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.

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.
* 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).
* History of allogeneic organ transplantation or graft-versus-host disease.
* Any live vaccines within 4 weeks before the first dose.
* Known mental illness or substance abuse that would interfere with trial complies.
* Subject is pregnant or lactating, or is expected to become pregnant or parent a child during the planned study period.
* Other conditions that investigators consider inappropriate for inclusion.

Where this trial is running

Beijing, Beijing Municipality and 13 other locations

• Peking University Third Hospital — Beijing, Beijing Municipality, China (Recruiting)
• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)
• Harbin Medical University Cancer Hospital — Haerbin, Heilongjiang, China (Not_yet_recruiting)
• Henan Cancer Hospital Affiliated Cancer Hospital of Zhengzhou University — Zhengzhou, Henan, China (Not_yet_recruiting)
• Renmin Hospital of Wuhan University — Wuhan, Hubei, China (Not_yet_recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Recruiting)
• Qilu Hospital of Shandong University — Jinan, Shandong, China (Not_yet_recruiting)
• The Affiliated Hospital of Qingdao University — Qingdao, Shandong, China (Recruiting)
• Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Enrolling_by_invitation)
• First Hospital of Shanxi Medcial University — Taiyuan, Shanxi, China (Not_yet_recruiting)
• West China Hospital of Sichuan University — Chengdu, Sichuan, China (Not_yet_recruiting)
• The Second Hospital of Tianjin Medical University — Tianjin, Tianjin Municipality, China (Recruiting)
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Tammy Wu, Ph.D

Conditions Non-Muscle-Invasive Bladder Cancer; NMIBC