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Brief Title: Cretostimogene Grenadenorepvec Given in Patients With Non-Muscular Invasive Bladder Cancer, Unresponsive to BCG

A Phase 3 Study of Cretostimogene Grenadenorepvec in Patients With Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus-Calmette-Guerin (BCG)

INTRODUCTION

  • Org Study ID: CG3002S
  • Secondary ID: N/A
  • NCT ID: NCT04452591
  • Sponsor: CG Oncology, Inc.

DESCRIPTION

This clinical trial will evaluate the activity of intravesical (IVE) administration of cretostimogene grenadenorepvec (CG0070) in patients with tissue pathology confirmed non-muscle invasive bladder cancer (NMIBC) who have Bacillus-Calmette-Guerin (BCG) unresponsive disease, with either carcinoma in situ (CIS) with or without Ta/T1 disease. When bladder cancer doesn’t respond to BCG, it can be tough to treat.

Cretostimogene grenadenorepvec is a selective oncolytic immunotherapy (OIT) that targets cancer cells that could change the treatment of BCG-unresponsive NMIBC. This treatment is designed to specifically target cancer cells while leaving healthy cells alone. This may mean fewer side effects compared to treatments that damage healthy cells too.

To learn more contact Joanna Horn at [email protected].

Explanation of this BOND-003 study

Guide to discussing the BOND-003 trial with your physician.

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.

  • Overall Status
    Recruiting
  • Start Date
    October 27, 2020
  • Phase
    Phase 3
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

CONDITION

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

ELIGIBILITY

Cohort C Inclusion Criteria
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
Cohort P Inclusion Criteria
* 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.

- * Have pathologically confirmed (WHO grading system employed for tumor grading) (Compérat 2019) BCG-unresponsive HG Ta/T1 papillary disease without CIS. Patients with BCG-unresponsive HG Ta/T1 papillary disease are those unlikely to benefit from and who will not be receiving further IVE 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. Specifically, the definition of BCG unresponsive HG Ta/T1 papillary disease without CIS will also require the following:
* Pathologically confirmed recurrent HG Ta/T1 papillary disease without CIS within 6 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).

- * Patients with HG Ta: 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).

- * Patients with HG T1: Patients may be eligible after the initial induction alone (5 of 6 doses of an induction course) as the qualifying BCG treatment.

- * Completion (last dose) of qualifying BCG treatment within 12 months of study enrollment.

- * Pathological confirmation of BCG-unresponsive HG Ta/T1 papillary disease without CIS within 14 days of study enrollment.

- * All pathology specimens 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; however, there should be no more than 12 months between cycles of BCG

- * Have all Ta and/or T1 disease resected, prior to study treatment (e.g., prior to Day 1 treatment).

- * Ineligible to receive radical cystectomy (medically unfit) or refusal of radical cystectomy based on Investigator assessment.

- * Demonstrate adequate organ function,

- * Patients must be willing to comply with study-mandated cystoscopies, urine cytology, imaging, biopsies, and other procedures for the duration of the trial
Cohort C and Cohort P Key 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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: CG Oncology

Role: Study Director

Affiliation: CG Oncology

Overall Contact

Name: JoAnn Horn

Phone: 516-456-1415

Email: [email protected]

LOCATION

Facility Status Contact
Facility: Mayo Clinic Cancer Center
Phoenix, Arizona 85054
United States
Status: Recruiting Contact: Contact
Clinical Trials Office All Mayo Clinic Locations
855-776-0015

Principal Investigator
Mark Tyson, MD

Facility: Arizona Institute of Urology
Tucson, Arizona 85704
United States
Status: Recruiting Contact: Principal Investigator
Jay Page, MD

Facility: Arkansas Urology
Little Rock, Arkansas 72211
United States
Status: Recruiting Contact: Contact
Johnathan Henderson

Facility: University of California - Irvine
Irvine, California 92868
United States
Status: Recruiting Contact: Contact
Steven Bereta

Principal Investigator
Edward Uchio, MD

Facility: University of Colorado
Aurora, Colorado 80045
United States
Status: Recruiting Contact: Contact
Janet Kukreja

Facility: MedStar Hospital
Washington, District of Columbia 20010
United States
Status: Recruiting Contact: Contact
Lambros Stamatakis

Facility: Mayo Clinic - Jacksonville
Jacksonville, Florida 32224
United States
Status: Recruiting Contact: Contact
Andrew Hendrix

Principal Investigator
Timothy Lyon, MD

Facility: Moffit Cancer Center
Tampa, Florida 33612
United States
Status: Recruiting Contact: Contact
Rodger Li

Facility: Emory University
Atlanta, Georgia 30322
United States
Status: Recruiting Contact: Contact
Misaki Mason

Principal Investigator
Shreyas Joshi, MD

Facility: University of Kansas
Kansas City, Kansas 66160
United States
Status: Recruiting Contact: Principal Investigator
Eugene Lee, MD

Facility: Chesapeake Urology
Severna Park, Maryland 21076
United States
Status: Recruiting Contact: Contact
Rian Dickstein

Facility: Mayo Rochester
Rochester, Minnesota 55905
United States
Status: Recruiting Contact: Contact
Paras Shah

Facility: Mercy Medical Center
Saint Louis, Missouri 63109
United States
Status: Recruiting Contact: Contact
Gautam Agarwal

Facility: Washington University
Saint Louis, Missouri 63130
United States
Status: Recruiting Contact: Contact
Woody Smelser

Facility: Specialty Clinical Research of St. Louis
Saint Louis, Missouri 63141
United States
Status: Recruiting Contact: Contact
Gregory Auffenberg

Facility: Duke University
Durham, North Carolina 27710
United States
Status: Recruiting Contact: Contact
Whitney Franz

Principal Investigator
Brant Inman, MD

Facility: Carolina Urologic
Myrtle Sound, North Carolina 29572
United States
Status: Recruiting Contact: Contact
Neal Shore

Facility: University of Toledo
Toledo, Ohio 43614
United States
Status: Recruiting Contact: Contact
Stephanie Smiddy

Principal Investigator
Firas G Petros, MD

Facility: University of Pennsylvania, Perelman School of Medicine
Philadelphia, Pennsylvania 19104
United States
Status: Recruiting Contact: Contact
Hanna Stambakio

Principal Investigator
Thomas Guzzo, MD

Facility: Carolina Urologic Research Center
Myrtle Beach, South Carolina 29572
United States
Status: Recruiting Contact: Contact
Ryan Sutton

Principal Investigator
Neal Shore, MD

Facility: Urology Associates- Nashville
Nashville, Tennessee 37209
United States
Status: Recruiting Contact: Contact
Gautam Jayram

Facility: Vanderbilt University Medical Center
Nashville, Tennessee 37232
United States
Status: Recruiting Contact: Contact
Pamela Steele

Principal Investigator
Sam Chang, MD

Facility: Urology San Antonio, PA
San Antonio, Texas 78229
United States
Status: Recruiting Contact: Contact
Kehkashan Arshad

Principal Investigator
Daniel Saltzstein, MD

Facility: Spokane Urology
Spokane, Washington 99202
United States
Status: Recruiting Contact: Contact
Shane Pearce