A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SIM0237 Alone or in Combination With BCG in NMIBC

March 22, 2024 updated by: Jiangsu Simcere Pharmaceutical Co., Ltd.

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 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)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

108

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100191
        • Not yet recruiting
        • Peking University Third Hospital
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Not yet recruiting
        • Sun Yat-sen University Cancer Center
        • Contact:
    • Henan
      • Zhengzhou, Henan, China, 450003
        • Not yet recruiting
        • Henan Cancer Hospital Affiliated Cancer Hospital of Zhengzhou University
        • Contact:
    • Hunan
      • Changsha, Hunan, China, 410031
    • Shandong
      • Qingdao, Shandong, China, 266071
    • Shanghai
      • Shanghai, Shanghai, China, 201321
        • Enrolling by invitation
        • Fudan University Shanghai Cancer Center
    • Tianjin
      • Tianjin, Tianjin, China, 300211
        • Not yet recruiting
        • The Second Hospital of Tianjin Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 2: BCG-unresponsive CIS (with or without Ta or T1 disease); b) Cohort 3: 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 biopsy if initial biopsy 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 within 2 weeks prior to the first dose.
  • Previous treatment with: a) Systematic drug administration for the purpose of treating NMIBC. b) Intravesical instillation for the treatment of NMIBC, but intravesical instillation of chemotherapy or BCG therapy beyond 4 weeks prior to the first dose and a single immediate instillation of chemotherapy within 4 weeks prior to the first dose are allowed. c) 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; Patients may be considered for enrollment if they have only upper urinary tract Ta/T1/CIS and have undergone radical nephrectomy more than 2 years prior to the first dose.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose escalation-mono
BCG-unresponsive high-risk NMIBC, receiving SIM0237 monotherapy intravesically. Induction period (QW for 6 weeks) + a 3-week maintenance course or a 6-week re-induction course at Month 3 + maintenance treatment (QW for 3 weeks) at Months 6, 9, 12, and 18 + optional maintenance treatment at Months 24, 30, and 36.
Drug: SIM0237
Several dose levels of SIM0237 will be administered as a single agent for evaluation
Drug: SIM0237
RD level of SIM0237 will be administered as a single agent for evaluation
Experimental: Dose escalation-combo
BCG-unresponsive high-risk NMIBC, receiving SIM0237 and BCG intravesically. Induction period (QW for 6 weeks) + a 3-week maintenance course or a 6-week re-induction course at Month 3 + maintenance treatment (QW for 3 weeks) at Months 6, 9, 12, and 18 + optional maintenance treatment at Months 24, 30, and 36.
Drug: SIM0237 and BCG
Several dose levels of SIM0237 will be administered in combination with a fixed dose of BCG for evaluation
Drug: SIM0237 and BCG
RD level of SIM0237 will be administered in combination with a fixed dose of BCG for evaluation
Experimental: Dose expansion-Cohort 1
BCG-unresponsive CIS, receiving SIM0237 monotherapy intravesically. Induction period (QW for 6 weeks) + a 3-week maintenance course or a 6-week re-induction course at Month 3 + maintenance treatment (QW for 3 weeks) at Months 6, 9, 12, and 18 + optional maintenance treatment at Months 24, 30, and 36.
Drug: SIM0237
Several dose levels of SIM0237 will be administered as a single agent for evaluation
Drug: SIM0237
RD level of SIM0237 will be administered as a single agent for evaluation
Experimental: Dose expansion-Cohort 2
BCG-unresponsive CIS, receiving SIM0237 and BCG intravesically. Induction period (QW for 6 weeks) + a 3-week maintenance course or a 6-week re-induction course at Month 3 + maintenance treatment (QW for 3 weeks) at Months 6, 9, 12, and 18 + optional maintenance treatment at Months 24, 30, and 36.
Drug: SIM0237 and BCG
Several dose levels of SIM0237 will be administered in combination with a fixed dose of BCG for evaluation
Drug: SIM0237 and BCG
RD level of SIM0237 will be administered in combination with a fixed dose of BCG for evaluation
Experimental: Dose expansion-Cohort 3
BCG-unresponsive high-risk Ta or T1, receiving SIM0237 and BCG intravesically. Induction period (QW for 6 weeks) + a 3-week maintenance course or a 6-week re-induction course at Month 3 + maintenance treatment (QW for 3 weeks) at Months 6, 9, 12, and 18 + optional maintenance treatment at Months 24, 30, and 36.
Drug: SIM0237 and BCG
Several dose levels of SIM0237 will be administered in combination with a fixed dose of BCG for evaluation
Drug: SIM0237 and BCG
RD level of SIM0237 will be administered in combination with a fixed dose of BCG for evaluation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose escalation:Dose limited toxicity (DLT)
Time Frame: DLT observation period (up to 21 days)
DLT observation period (up to 21 days)
Dose escalation: Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Time Frame: through study completion, an average of 5 years
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
Time Frame: Approximately 3 months
Complete response (CR) rate at Month 3 of Cohort 1 and Cohort 2
Approximately 3 months
Dose escalation: Percentage of participants experiencing AE related dose interruptions and dose delays, dose intensity
Time Frame: through study completion, an average of 5 years
Occurrence of AE related dose interruptions, dose delays and dose intensity
through study completion, an average of 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jiangsu Simcere Pharmaceutical Co., Ltd.

Collaborators

Shanghai Xianxiang Medical Technology Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 23, 2024

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

December 1, 2030

Study Registration Dates

First Submitted

December 7, 2023

First Submitted That Met QC Criteria

December 29, 2023

First Posted (Actual)

January 2, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2024

Last Update Submitted That Met QC Criteria

March 22, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SIM0237-102

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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