RC48-ADC in Combination With Gemcitabine in High Risk NMIBC Subjects

NCT05943379 | Recruiting Phase 2

• 1 other identifier: RC48-C028
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, participants with high risk non-muscle-invasive bladder cancer (NMIBC) who are BCG Naïve or BCG Unresponsive and are considered ineligible for or have refused to undergo radical cystectomy, will receive RC48-ADC in combination with gemcitabine.

Conditions

NMIBC

Outcome Measures

Primary Outcomes (1)

• 12-month Disease Free Survival Rate

  12 month

Secondary Outcomes (7)

• Complete Response Rate

  3 month

• 6-month Disease Free Survival Rate

  6 month

• 18-month Disease Free Survival Rate

  18 month

• 24-month Disease Free Survival Rate

  24 month

• Recurrence-free survival

  up to 24 months

Study Arms (2)

cohort 1

EXPERIMENTAL

BCG Naïve

Drug: RC48-ADC in Combination with gemcitabine

cohort 2

EXPERIMENTAL

BCG Unresponsive

Drug: RC48-ADC in Combination with gemcitabine

Interventions

RC48-ADC in Combination with gemcitabine DRUG

RC48-ADC IV (intravenous) 2.0mg/kg IV, Q2W, 8W; Q4W, 40W Gemcitabine Intravesical 1000mg induction QW,8W; maintenance Q4W,40W

cohort 1; cohort 2

Eligibility Criteria

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

You may qualify if:

• \. Voluntary consent to participate in the study and sign an informed consent form.
• \. Male or female, age ≥ 18 years. 3. Disease satisfies.
• Diagnosis in accordance with the Chinese Guidelines for the Treatment of Bladder Cancer (2022) high-risk non-muscle invasive bladder cancer (NMIBC) and meeting any of the following ± carcinoma in situ (CIS): 1. stage T1 tumor of any grade; 2. high-grade tumor; 3. multiple and/or recurrent tumors, with recurrent tumors excluding low-grade solitary tumors.
• Histopathological satisfaction of uroepithelial carcinoma predominant by histopathology, confirming the absence of muscular infiltration.
• Completion of TURBT and resection of all visible lesions within 3 weeks prior to study dosing.
• Clinical staging (cTa/T1±CIS, N0, M0) and absence of distant metastases as assessed by imaging (which needs to include at least CTU) within 3 months prior to enrollment.
• \. 4. Prior BCG treatment.
• Cohort 1 is high-risk NMIBC patients who have not received prior BCG therapy: high-risk NMIBC patients who have not received prior BCG therapy due to subjective and objective conditions, including one of the following 1. patient refusal to receive BCG therapy; 2. presence of contraindications to BCG therapy; 3. BCG inaccessibility.
• Cohort 2 was high-risk NMIBC patients with BCG non-response, and BCG non-response met any of the following: 1. presence of persistent/recurrent high-risk NMIBC within 12 months (±1 month) of completing adequate BCG therapy; 2. high-grade T1 disease at first assessment after induction phase BCG therapy. Note: Adequate BCG therapy is defined as at least 5 BCG bladder instillations completed within 2 months and at least 2 BCG bladder instillations completed in any 6 consecutive weeks over the next 10 months, i.e., at least "5+2" BCG bladder instillations completed over an approximately 12-month period.
• \. Subjects who have been assessed by a urologist to be unsuitable for radical bladder cancer surgery or who have refused radical bladder cancer surgery.
• \. Subjects whose tumor tissue obtained by TURBT within 3 weeks meets 1+, 2+ or 3+ HER2 expression by immunohistochemistry (IHC) at the study center.
• \. ECOG physical status score of 0-2. 8. Adequate cardiac, bone marrow, liver, and renal function, which should meet the following criteria within 7 days prior to study dosing (normal values are based on the clinical trial center).
• Left ventricular ejection fraction ≥ 50%.
• Hemoglobin ≥ 9 g/dL.
• Absolute neutrophil count (ANC) ≥ 1.5×109/L.

You may not qualify if:

• muscle-invasive bladder cancer (T2 and above) and/or with regional lymph nodes and distant metastases
• Combined extra-vesical (i.e. urethral, ureteral or renal pelvis) uroepithelial carcinoma.
• Received any other antitumor therapy, such as chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc., within 4 weeks prior to study dosing, excluding 1 dose of infusion chemotherapy completed immediately after TURBT.
• Have not recovered from an adverse event caused by a previously applied antineoplastic agent to CECAT 5.0 grade 0-1 within 2 weeks prior to the start of study dosing.
• Those who have undergone major surgery within 4 weeks prior to the start of study dosing or who are scheduled to undergo major surgery during the trial.
• Serum virological tests (based on the normal values of the study center).
• Positive HBsAg or HBcAb test result with a positive HBVDNA copy number.
• Positive HCVAb test result together with a positive HCVRNA test result.
• Positive HIVAb test result.
• live vaccine received within 4 weeks prior to the start of study dosing or scheduled to receive any vaccine (except novel coronavirus vaccine) during the study period.
• heart failure classified as grade 3 or higher by the New York Heart Association (NYHA) of America.
• the presence of a serious arterial/venous thrombotic event or cardiovascular accident such as deep vein thrombosis, pulmonary embolism, cerebral infarction, cerebral hemorrhage, or myocardial infarction within 6 months prior to study dosing, except for lacunar cerebral infarction that is asymptomatic and does not require clinical intervention
• the presence of an active infection requiring systemic treatment, such as active tuberculosis
• the presence of active, unstably controlled systemic disease or serious comorbidity as judged by the investigator, including diabetes mellitus, hypertension, cirrhosis, interstitial pneumonia, obstructive pulmonary disease, complications that could cause the subject to undergo intravesical therapy and/or general anesthesia
• having any other disease, metabolic abnormality, physical examination abnormality or laboratory test abnormality that, in the judgment of the investigator, gives reason to suspect that the patient has a disease or condition that is inappropriate for the use of the study drug or that will affect the interpretation of the study results, or that places the patient at high risk

Sponsors & Collaborators

• RemeGen Co., Ltd.: lead

Study Sites (1)

Peking University First Hosptital

Beijing, Beijing Municipality, 100034, China

RECRUITING

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Interventions

Gemcitabine

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: July 13, 2023
• Study Start: June 8, 2023
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 13, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)