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

Non Muscle Invasive Bladder Cancer Clinical Trial

— BOND-003  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04452591
• Other study ID #: CG3002S
• Status: Recruiting
• Phase: Phase 3
• Start date: October 27, 2020
• Est. completion date: December 24, 2029

Study information

• Verified date: April 2024
• Source: CG Oncology, Inc.
• Contact: JoAnn Horn
• Phone: 516-456-1415
• Email: joann.horn[@]CGoncology.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 190
• Est. completion date: December 24, 2029
• Est. primary completion date: December 24, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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 8 weeks 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

Related Conditions & MeSH terms

• Non Muscle Invasive Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Biological:
• Cretostimogene Grenadenorepvec
Engineered Oncolytic Adenovirus

Other:
• n-dodecyl-B-D-maltoside
Transduction-enhancing agent.

Locations

Country	Name	City	State
Australia	Barwon Health, University Hospital Geelong	Geelong
Australia	Royal Melbourne Hospital	Melbourne
Australia	Wollongong Private Hospital	Wollongong
Japan	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	Matsumoto
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	Keio University Hospital	Tokyo
Japan	Ehime University Hospital	Toon
Japan	Toyoma University Hospital	Toyoma
Japan	Wakayama Medical University Hospital	Wakayama
Japan	National Hospital Organization Yokohama Medical Center	Yokohama
Korea, Republic of	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	Korea University Anam Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	The Catholic University of Korea	Seoul
Taiwan	Keelung Chang Gung Memorial Hospital	Keelung
Taiwan	Keelung Chang Gung Memorial Hospital	Keelung City
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United States	Emory University	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Duke University	Durham	North Carolina
United States	University of California - Irvine	Irvine	California
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	University of Kansas	Kansas City	Kansas
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Carolina Urologic	Myrtle Sound	North Carolina
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University of Pennsylvania, Perelman School of Medicine	Philadelphia	Pennsylvania
United States	Mayo Clinic Cancer Center	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota
United States	Mayo Rochester	Rochester	Minnesota
United States	Mercy Medical Center	Saint Louis	Missouri
United States	Urology San Antonio, PA	San Antonio	Texas
United States	Chesapeake Urology	Severna Park	Maryland
United States	Spokane Urology	Spokane	Washington
United States	Moffit Cancer Center	Tampa	Florida
United States	University of Toledo	Toledo	Ohio
United States	Arizona Institute of Urology	Tucson	Arizona
United States	MedStar Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
CG Oncology, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Japan,  Korea, Republic of,  Taiwan, 

Outcome

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