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

NCT04452591 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: CG3002S
• Study Type: interventional
• Target: 190
• Locations: 6 countries
• Sites: 86

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

Conditions

Non Muscle Invasive Bladder Cancer; High-grade Ta/ T1 Papillary Disease Bladder Cancer

Keywords

high-grade Ta papillary disease; high-grade T1 papillary disease; carcinoma in situ; Bacillus-Calmette-Guerin unresponsive

Outcome Measures

Primary Outcomes (2)

• Cohort C:

  To determine the Complete Response rate at any time in patients with BCG-unresponsive CIS with or without concomitant HG Ta/T1 papillary disease.

  36 months

• Cohort P:

  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.

  36 months

Secondary Outcomes (8)

• Cohort C: Duration of response (DOR)

  36 months

• Cohort C and Cohort P: Assess high-grade reoccurrence free survival (RFS)

  up to 60 months

• Cohort C and Cohort P: Assess progression free survival (PFS )

  up to 60 months

• Cohort C:Complete Response rate at 12 months

  12 months

• Cohort C and Cohort P : Cystectomy free survival

  up to 60 months

Study Arms (2)

Cohort C(All Countries):Enrollment Closed

EXPERIMENTAL

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.

Biological: Cretostimogene Grenadenorepvec; Other: n-dodecyl-B-D-maltoside

Cohort P(Japan and United States Only) :Open to Enrollment

EXPERIMENTAL

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.

Biological: Cretostimogene Grenadenorepvec; Other: n-dodecyl-B-D-maltoside

Interventions

Cretostimogene Grenadenorepvec BIOLOGICAL

Engineered Oncolytic Adenovirus

Cohort C(All Countries):Enrollment Closed; Cohort P(Japan and United States Only) :Open to Enrollment

n-dodecyl-B-D-maltoside OTHER

Transduction-enhancing agent.

Also known as: DDM

Cohort C(All Countries):Enrollment Closed; Cohort P(Japan and United States Only) :Open to Enrollment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible for participation in this trial, the patient must:
• Be ≥18 years of age (or legal age of majority in the jurisdiction) on day of signing informed consent.
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Have pathologically confirmed (WHO grading system employed for tumor grading) (Compérat 2019) BCG unresponsive CIS. Patients with BCG unresponsive CIS are those unlikely to benefit from, and who will not be receiving, further intravesical BCG. There is no maximum limit to the amount of prior BCG treatment, but maintenance BCG should be administered on a schedule consistent with standard induction-maintenance protocols (e.g., BCG weekly × 6 then weekly × 3 weeks administered at Months 3, 6, 12, 18, 24, and 36). Specifically, the definition of BCG unresponsive CIS will also require the following:
• Pathologically confirmed relapsed or persistent CIS (with or without HG Ta or HG T1 disease) within 12 months of completion (last dose) of adequate BCG treatment for HGUC (e.g., CIS, HG Ta, HG T1, or a combination of these HGUC pathologies).
• Completion of qualifying BCG treatment (e.g., "5+2" minimum exposure) within 12 months of the initial qualifying dose of BCG (e.g., induction and initial maintenance or re-induction cycle must be completed over no more than a 12-month period of time).
• Pathological confirmation of BCG unresponsive CIS within 8 weeks of study enrollment.
• CIS specimen must be predominantly urothelial (transitional cell) and have less than 50% variant (e.g., sarcomatoid, squamous etc. component) histology.
• No maximum limit to the amount of BCG administered but maintenance BCG should be administered on a schedule consistent with the SWOG 8507 regimen (Lamm 2000).
• Have all Ta and/or T1 disease resected and all CIS resected or fulgurated, as feasible, prior to study treatment (e.g., prior to Day 1 treatment).
• Ineligible to receive radical cystectomy (medically unfit) or refusal of radical cystectomy according to Investigator assessment.
• Demonstrate adequate organ function
• Patients must be willing to comply with study mandated cystoscopies, urine cytology, urograms, biopsies, and other procedures (including TURBT or other resection for all Ta/T1 disease) for the duration of the study. Patients who withdraw consent for these procedures will be withdrawn from the trial
• Be ≥18 years of age (or legal age of majority in the jurisdiction) on day of signing informed consent
• Have ECOG performance status of 0 to 2.

You may not qualify if:

• 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

Sponsors & Collaborators

• CG Oncology, Inc.: lead

Study Sites (86)

Urology Centers Alabama

Homewood, Alabama, 35209, United States

Location

BCG Oncology

Phoenix, Arizona, 85032, United States

Location

Mayo Clinic Cancer Center

Phoenix, Arizona, 85054, United States

Location

Arizona Institute of Urology

Tucson, Arizona, 85704, United States

Location

Arkansas Urology

Little Rock, Arkansas, 72211, United States

Location

University of California - Irvine

Irvine, California, 92868, United States

Location

American Insititute of Research

Los Angeles, California, 90017, United States

Location

Genesis Research

Sherman Oaks, California, 91411, United States

Location

Genesis Research LLC

Torrance, California, 90505, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Colorado Clinical Research

Lakewood, Colorado, 80228, United States

Location

Urology Associates, Research Department

Lone Tree, Colorado, 80124, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Moffit Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Urology Indiana LLC

Greenwood, Indiana, 46143, United States

Location

The University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Wichita Urology

Wichita, Kansas, 67226, United States

Location

Southern Urology

Lafayette, Louisiana, 70508, United States

Location

Chesapeake Urology

Hanover, Maryland, 21076, United States

Location

Chesapeake Urology

Severna Park, Maryland, 21076, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Mayo Rochester

Rochester, Minnesota, 55905, United States

Location

Mercy Medical Center

St Louis, Missouri, 63109, United States

Location

Washington University

St Louis, Missouri, 63130, United States

Location

Specialty Clinical Research of St. Louis

St Louis, Missouri, 63141, United States

Location

New Jersey Premier Urology

Edison, New Jersey, 08837, United States

Location

Our Lady of Lourdes

Binghamton, New York, 13905, United States

Location

Stony Brook University

Stony Brook, New York, 11794, United States

Location

Montifiore Medical Center

The Bronx, New York, 10461, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Wake Forest

Winston-Salem, North Carolina, 27157, United States

Location

University of Toledo

Toledo, Ohio, 43614, United States

Location

Keystone Urology Specialists

Lancaster, Pennsylvania, 17601, United States

Location

University of Pennsylvania, Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Prisma Health - Regional Urology

Greenville, South Carolina, 29605, United States

Location

Carolina Urologic Research Center LLC

Myrtle Beach, South Carolina, 29572, United States

Location

Conrad Pearson Clinic

Germantown, Tennessee, 38138, United States

Location

Urology Associates- Nashville

Nashville, Tennessee, 37209, United States

Location

Vanderbilt University Medical Center, Dept of Urology

Nashville, Tennessee, 37232, United States

Location

Houston Metro Urology

Houston, Texas, 77027, United States

Location

Urology San Antonio, PA

San Antonio, Texas, 78229, United States

Location

Baylor Scott & White Medical Center-Temple

Temple, Texas, 76508, United States

Location

Spokane Urology

Spokane, Washington, 99202, United States

Location

Southside Cancer Care Center

Miranda, New South Wales, 2228, Australia

Location

Barwon Health, University Hospital Geelong, Andrew love cancer center

Geelong, Australia

Location

Royal Melbourne Hospital

Melbourne, Australia

Location

CHUM Center for Research

Montreal, Quebec, H2X0A9, Canada

Location

MUHC Glen-Ceders Cancer Centre, Oncology Pharmacy

Montreal, Quebec, H4A 3JI, Canada

Location

The Jikei University Kashiwa Hospital

Kashiwa-shi, Chiba, 227-8567, Japan

Location

Ehime University Hospital

Tōon, Ehime, 791-0295, Japan

Location

Sapporo Medical University Hospital

Sapporo, Hokkaido, 060-8543, Japan

Location

University of Tsukuba Hospital

Kandori, Ibaraki, 305-8576, Japan

Location

Kagawa Rosai Hospital

Marugame, Kagawa-ken, 763-8502, Japan

Location

St. Marianna University Hospital

Kawasaki, Kanagawa, 216-8511, Japan

Location

National Hospital Organization Yokohama Medical Center

Yokohama, Kanagawa, 245-8575, Japan

Location

National Hospital Organization Kyoto Medical Center

Kyoto, Kyoto, 6128555, Japan

Location

Nara Medical University Hospital

Kashihara, Nara, 634-8522, Japan

Location

Okayama University Hospital

Okayama, Okayama-ken, 700-8558, Japan

Location

Osaka City University Hospital

Osaka, Osaka, 545-8586, Japan

Location

Osaka Medical and Pharmaceutical University Hospital

Osaka, Osaka, 569-8686, Japan

Location

Saitama City Hospital

Saitama, Saitama, 3368522, Japan

Location

Shizuoka General Hospital

Shizuoka, Shizuoka, 420-8527, Japan

Location

Keio University Hospital

Matsumoto, Tokyo, 160-8582, Japan

Location

Keio University Hospital

Tokyo, Tokyo, 160-8582, Japan

Location

Toyama University Hospital

Toyama, Toyama, 930-0194, Japan

Location

Wakayama Medical University Hospital

Wakayama, Wakayama, 6418510, Japan

Location

National Cancer Center Hospital East

Chiba, Japan

Location

Nagoya University Hospital

Fujita, Japan

Location

Hirosaki University Hospital

Hashimoto, Japan

Location

Chugoku Rosai Hospital

Hiroshima, Japan

Location

Shinshu University Hospital

Ishizuka, Japan

Location

Osaka International Cancer Institute

Osaka, Japan

Location

Kitsato University Hospital

Sagamihara, Japan

Location

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Pusan National University Yangsan Hospital

Gyeongsang, 50612, South Korea

Location

Chonnam National University Hwasun Hospital

Jeongnam, 58128, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

The Catholic University of Korea

Seoul, 06591, South Korea

Location

Keelung Chang Gung Memorial Hospital

Keelung, 20401, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms; Carcinoma in Situ

Interventions

dodecyl maltoside

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• CG Oncology

  CG Oncology

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 26, 2020
• First Posted: June 30, 2020
• Study Start: October 27, 2020
• Primary Completion (Estimated): June 16, 2030
• Study Completion (Estimated): December 24, 2031
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); JP (25); TW (4); AU (3); US (45); KR (7)