Study of Cretostimogene Given in Patients With Non-Muscle Invasive Bladder Cancer ,Unresponsive to Bacillus-Calmette-Guerin

Phase 3

Recruiting

• Conditions: High-grade Ta/ T1 Papillary Disease Bladder Cancer; Non Muscle Invasive Bladder Cancer
• Interventions: Biological: Cretostimogene Grenadenorepvec; Other: n-dodecyl-B-D-maltoside

• Registration Number: NCT04452591
• Lead Sponsor: CG Oncology, Inc.

Brief Summary

This is a Phase 3, open-label, single arm trial designed to evaluate Cretostimogene patients with NMIBC who have failed prior BCG therapy. Up to approximately 115 CIS bladder cancer patients with or without HG Ta or HG T1 papillary disease will be enrolled under the original protocol through Amendment 4, which will comprise Cohort C. Cohort C is closed to enrollment.

Under Amendment 5-1, Cohort P was added to enroll up to 70 patients with HG Ta/T1 papillary bladder cancer.

Under Amendment 6, the target number of patients enrolled in Cohort P was increased to 75. Cohort P is open to enrollment

Cohort C and Cohort P will be analyzed and reported separately. Patients will have had to fail prior BCG therapy which is defined as having persistent or recurrent disease within 12 months (Cohort C) or 6 months (Cohort P) following the completion of adequate BCG therapy for HGUC

Detailed Description

Cohort C(All Countries) :

An open-label trial designed to evaluate Cretostimogene + DDM in patients with NMIBC who have failed prior BCG therapy. Single treatment arm that enrolled 115 patients with carcinoma in situ with or without concomitant high-grade Ta or T1 papillary disease

BCG failure is defined as a persistent or recurrent disease within 12 months of completion of adequate BCG therapy.

Cohort P(Japan and the United States Only):

To determine the all-cause High Grade Event Free Survival (HG-EFS) of cretostimogene in up to 75 patients with BCG-unresponsive HG Ta/T1 papillary disease without CIS.

BCG failure is defined as a persistent or recurrent disease within 6 months of completion of adequate BCG therapy.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2020-06-26
• Study First Submitted QC: 2020-06-29
• Study First Posted: 2020-06-30
• Study Start: 2020-10-27
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-27
• Last Update Posted: 2024-12-02
• Primary Completion: 2027-12-24
• Study Completion: 2029-12-24

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 190

Inclusion Criteria

Not provided

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Exclusion Criteria

• Has current or past history of muscle invasive (T2 or higher stage) or locally advanced (T3/T4, any N) or metastatic bladder cancer.
• Any HGUC as T1, HG Ta, or CIS in the upper genitourinary tract or prostatic urethra (including CIS of the urethra) within 24 months prior to enrollment OR any history of T2 or higher stage urothelial carcinoma in the upper genitourinary tract (kidneys, renal collecting systems, ureters).
• Has received systemic anti-cancer therapy, including investigational agents, within 4 weeks of Day 1.
• Has had prior systemic treatment (with the exception of checkpoint inhibitor therapy), radiation therapy, or surgery for bladder cancer other than TURBT or bladder biopsies.
• Has any of the following within the 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, pulmonary embolus, uncontrolled hypertension, or uncontrolled congestive heart failure.
• Cannot tolerate study-related biopsies, IVE administration, or 1-hour bladder hold of cretostimogene.
• IVE therapy within 8 weeks prior to beginning study treatment with the exception of cytotoxic agents (e.g., Mitomycin C, gemcitabine, doxorubicin and epirubicin) when administered as a single instillation immediately following a TURBT procedure which is permitted 14 or more days prior to beginning study treatment

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort P(Japan and United States Only) :Open to Enrollment	n-dodecyl-B-D-maltoside	HG Ta/T1 papillary disease bladder cancer patients. In Cohort P, cretostimogene will be administered at a dose of 1 × 1012vp IVE following instillation of 5% DDM. Cretostimogene will be administered every week for 6 treatments on Weeks 1, 2, 3, 4, 5, and 6. If the patient has recurrence at Week 13 or any timepoint, the patient will receive a second induction of 6 weekly treatments (Weeks 13, 14, 15, 16, 17, and 18.). If the tumor has not returned they will receive 3 weekly treatments every 12 weeks (approximately 3 months) starting Weeks 13, 14, and 15 through Week 51 (approximately 12 months), and then every 6 months starting at Weeks 73, 74, and 75 (approximately 18 months) through Month 36.
Cohort C(All Countries):Enrollment Closed	Cretostimogene Grenadenorepvec	Patients with CIS with or without HG Ta/T1 papillary disease. Cretostimogene will be administered intravesically following a series of bladder washes with 5% DDM and normal saline. Cretostimogene will be administered weekly x 6 on Weeks 1, 2, 3, 4, 5, and 6. If the patient has disease recurrence at Week 13, they will receive another cycle of 6 weekly treatments. If there is no disease present at Week 13 then the patient will receive 3 weekly treatments. Cohort C(All Countries):Beginning at Week 25, patients will receive weekly x 3 treatments every 12 weeks through week 51 then every 6 months and then a last treatment at Weeks 73, 74, and 75 until the tumor returns or study treatment is completed at Week 97. Cohort C Extension( Japan and the US) At Week 25, patients will receive weekly x 3 treatments every 12 weeks through week 51 then every 6 months starting at Weeks 73, 74, and 75 through Weeks 157, 158, and 159 until the tumor returns or study treatment is completed at Week 159.
Cohort C(All Countries):Enrollment Closed	n-dodecyl-B-D-maltoside	Patients with CIS with or without HG Ta/T1 papillary disease. Cretostimogene will be administered intravesically following a series of bladder washes with 5% DDM and normal saline. Cretostimogene will be administered weekly x 6 on Weeks 1, 2, 3, 4, 5, and 6. If the patient has disease recurrence at Week 13, they will receive another cycle of 6 weekly treatments. If there is no disease present at Week 13 then the patient will receive 3 weekly treatments. Cohort C(All Countries):Beginning at Week 25, patients will receive weekly x 3 treatments every 12 weeks through week 51 then every 6 months and then a last treatment at Weeks 73, 74, and 75 until the tumor returns or study treatment is completed at Week 97. Cohort C Extension( Japan and the US) At Week 25, patients will receive weekly x 3 treatments every 12 weeks through week 51 then every 6 months starting at Weeks 73, 74, and 75 through Weeks 157, 158, and 159 until the tumor returns or study treatment is completed at Week 159.
Cohort P(Japan and United States Only) :Open to Enrollment	Cretostimogene Grenadenorepvec	HG Ta/T1 papillary disease bladder cancer patients. In Cohort P, cretostimogene will be administered at a dose of 1 × 1012vp IVE following instillation of 5% DDM. Cretostimogene will be administered every week for 6 treatments on Weeks 1, 2, 3, 4, 5, and 6. If the patient has recurrence at Week 13 or any timepoint, the patient will receive a second induction of 6 weekly treatments (Weeks 13, 14, 15, 16, 17, and 18.). If the tumor has not returned they will receive 3 weekly treatments every 12 weeks (approximately 3 months) starting Weeks 13, 14, and 15 through Week 51 (approximately 12 months), and then every 6 months starting at Weeks 73, 74, and 75 (approximately 18 months) through Month 36.

Primary Outcome Measures

Name	Time	Method
Cohort P:	36 months	To determine the high-grade EFS of cretostimogene in patients with BCG-unresponsive HG Ta/T1 papillary disease without CIS.Ta/T1 papillary disease without CIS.
Cohort C:	36 months	To determine the Complete Response rate at any time in patients with BCG-unresponsive CIS with or without concomitant HG Ta/T1 papillary disease.

Secondary Outcome Measures

Name	Time	Method
Cohort C: Duration of response (DOR)	36 months	Median duration of response in patients with a CR or PR in subjects
Cohort C:Complete Response rate at 12 months	12 months
Cohort C: Reoccurrence free survival	up to 60 months
Cohort C and Cohort P: Assess progression free survival (PFS )	up to 60 months
Cohort C and Cohort P : Cystectomy free survival	up to 60 months
Cohort C: Assess overall survival	up to 60 months
Cohort C and Cohort P: Assess high-grade reoccurrence free survival (RFS)	up to 60 months
Cohort C and Cohort P: Evaluate the safety of Cretostimogene	36 months

Trial Locations

Locations (71)

Colorado Clinical Research; 🇺🇸 Lakewood, Colorado, United States

Urology Associates; 🇺🇸 Lone Tree, Colorado, United States

Urology of Indiana; 🇺🇸 Greenwood, Indiana, United States

Wichita Urology; 🇺🇸 Wichita, Kansas, United States

Southern Urology; 🇺🇸 Lafayette, Louisiana, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Keystone Urology Specialists; 🇺🇸 Lancaster, Pennsylvania, United States

Conrad Pearson Clinic; 🇺🇸 Germantown, Tennessee, United States

Houston Metro Urology; 🇺🇸 Houston, Texas, United States

Mayo Clinic Cancer Center; 🇺🇸 Phoenix, Arizona, United States

Arizona Institute of Urology; 🇺🇸 Tucson, Arizona, United States

Arkansas Urology; 🇺🇸 Little Rock, Arkansas, United States

University of California - Irvine; 🇺🇸 Irvine, California, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

MedStar Hospital; 🇺🇸 Washington, District of Columbia, United States

Mayo Clinic - Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Moffit Cancer Center; 🇺🇸 Tampa, Florida, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

University of Kansas; 🇺🇸 Kansas City, Kansas, United States

Chesapeake Urology; 🇺🇸 Severna Park, Maryland, United States

Mayo Rochester; 🇺🇸 Rochester, Minnesota, United States

Mercy Medical Center; 🇺🇸 Saint Louis, Missouri, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Specialty Clinical Research of St. Louis; 🇺🇸 Saint Louis, Missouri, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

Carolina Urologic; 🇺🇸 Myrtle Sound, North Carolina, United States

University of Toledo; 🇺🇸 Toledo, Ohio, United States

University of Pennsylvania, Perelman School of Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States

Carolina Urologic Research Center; 🇺🇸 Myrtle Beach, South Carolina, United States

Urology Associates- Nashville; 🇺🇸 Nashville, Tennessee, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Urology San Antonio, PA; 🇺🇸 San Antonio, Texas, United States

Spokane Urology; 🇺🇸 Spokane, Washington, United States

Barwon Health, University Hospital Geelong; 🇦🇺 Geelong, Australia

Royal Melbourne Hospital; 🇦🇺 Melbourne, Australia

Wollongong Private Hospital; 🇦🇺 Wollongong, Australia

National Cancer Center Hospital East; 🇯🇵 Chiba, Japan

Nagoya University Hospital; 🇯🇵 Fujita, Japan

Hirosaki University Hospital; 🇯🇵 Hashimoto, Japan

Chugoku Rosai Hospital; 🇯🇵 Hiroshima, Japan

Shinshu University Hospital; 🇯🇵 Ishizuka, Japan

University of Tsukuba Hospital; 🇯🇵 Kandori, Japan

Nara Medical University Hospital; 🇯🇵 Kashihara, Japan

The Jikei University Kashiwa Hospital; 🇯🇵 Kashiwa, Japan

St. Marianna University Hospital; 🇯🇵 Kikuchi, Japan

National Hospital Organization Kyoto Medical Center; 🇯🇵 Kyoto, Japan

Kagawa Rosai Hospital; 🇯🇵 Marugame, Japan

Keio University Hospital; 🇯🇵 Tokyo, Japan

Okayama University Hospital; 🇯🇵 Okayama, Japan

Osaka City University Hospital; 🇯🇵 Osaka, Japan

Osaka Medical and Pharmaceutical University Hospital; 🇯🇵 Osaka, Japan

Kitsato University Hospital; 🇯🇵 Sagamihara, Japan

Saitama City Hospital; 🇯🇵 Saitama, Japan

Sapporo Medical University Hospital; 🇯🇵 Sapporo, Japan

Shizuoka General Hospital; 🇯🇵 Shizuoka, Japan

Ehime University Hospital; 🇯🇵 Toon, Japan

Toyoma University Hospital; 🇯🇵 Toyoma, Japan

Wakayama Medical University Hospital; 🇯🇵 Wakayama, Japan

National Hospital Organization Yokohama Medical Center; 🇯🇵 Yokohama, Japan

Pusan National University Hospital; 🇰🇷 Busan, Korea, Republic of

National Cancer Center; 🇰🇷 Goyang-si, Korea, Republic of

Pusan National University Yangsan Hospital; 🇰🇷 Gyeongsang, Korea, Republic of

Chonnam National University Hwasun Hospital; 🇰🇷 Jeongnam, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Korea University Anam Hospital; 🇰🇷 Seoul, Korea, Republic of

Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

The Catholic University of Korea; 🇰🇷 Seoul, Korea, Republic of

Keelung Chang Gung Memorial Hospital; 🇨🇳 Keelung, Taiwan

China Medical University Hospital; 🇨🇳 Taichung, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan