A Study of Cadonilimab（AK104）Combined With Standard Treatment for Function Preservation in Urinary System Tumors

A Prospective, Open Label, Dual Cohort Study of Cadonilimab（AK104）Combined With Standard Treatment for Function Preservation in Urinary System Tumors

This is an open label, dual cohort ,phase II study to explore efficacy and safety of cadonilimab(PD-1/CTLA-4 Bispecific Antibody) combined with standard regimen neoadjuvant treatment in urothelial carcinoma（UC） and renal cell carcinoma（RCC）, with evaluating successful preservation rate of bladder/kidney.

Study Overview

• Status: Not yet recruiting
• Conditions: Urinary System Tumor
• Intervention / Treatment: Drug: Cadonilimab plus chemotherapy; Drug: Cadonilimab plus TKI

Detailed Description

UC and RCC confirmed by histopathology or cytology prior have not received systematic treatment, who had indications for surgical resection and were difficult to preserve organ function after surgery or were partially resection but the patients have a strong desire to preserve organ function. This study enrolled 20 cases in each cohort of UC and RCC，pts received neoadjuvant treatment containing cadonilimab for no more than 6 cycles.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liu Huang, Clinical Professor; Phone Number: 63639656; Email: huangliu@tjh.tjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntary agreement to provide written informed consent.
• Male or female, Age ≥ 18 years.
• Predicted survival ≥ 12 weeks.
• Histologically confirmed diagnosis of urothelial carcinoma（UC） and renal cell carcinoma（RCC）.
• Prior no antitumor systematic treatment .
• Have clinically non-metastatic high risk urothelial carcinoma (cT2-T4a, N0-3, M0) .
• High risk renal cell carcinoma (≥ T2Nx or TanyN+)，include subjects with only Oligotransfer.
• Willing to undergo surgical resection and were difficult to preserve organ function after surgery or were partially resection but the patients have a strong desire to preserve organ function.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Adequate organ function, evidenced by the following laboratory results within 7 days prior to the study treatment.
• Male and female participants are eligible to participate if they agree to the contraception use as per study protocol.
• Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

Exclusion Criteria:

• Has received other antitumor therapy before planned start of trial treatment.
• History of major surgery within 4 weeks of planned start of trial treatment.
• Diagnosed with HBsAg, HBcAb positive and HBV DNA copy positive, or HCVAb positive, or HIVAb positive.
• Has received a live virus vaccine within 4 weeks of planned start of trial treatment.
• NYHA Class III heart failure.
• Suffering from active infection requiring systemic treatment.
• Uncontrolled hypertension, diabetes, Interstitial lung Disease, or COPD;
• Treated with systemic treatment (e.g. immunomodulators, corticosteroids or immunosuppressants) for the autoimmune disease within 2 years prior to the study treatment.
• History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Pregnancy or lactation.
• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UC; Patients will receive AK104 (10mg/kg ,Q3W，intravenously) plus standard regimen （gemcitabine or albumin paclitaxel) neoadjuvant treatment with no more than 6 cycles.	Drug: Cadonilimab plus chemotherapy; AK104 (10mg/kg ,Q3W，intravenously) plus chemotherapy（e.g. gemcitabine or albumin paclitaxel，dosage based on guidelines or instructions）
Experimental: RCC; Patients will receive AK104 (10mg/kg ,Q3W，intravenously) plus standard regimen （TKI，e.g. sunitinib, pezopanib) neoadjuvant treatment with no more than 6 cycles.	Drug: Cadonilimab plus TKI; Patients will receive AK104 (10mg/kg ,Q3W，intravenously) plus TKI（e.g. sunitinib, pezopanib，dosage based on guidelines or instructions)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bladder/Kidney Preservation rate	Evaluating the impact of neoadjuvant therapy on organ preservation function	Up to approximately 18 Weeks (Time of surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	percentage of participants with a complete response (CR) or partial response (PR)	Up to approximately 18 Weeks
Rate of Pathologic Response	No residual tumor (ypT0N0) and partial response (ypTis-1N0) in surgical specimen.	Up to approximately 18 Weeks (Time of surgery) ]
Overall Survival (OS)	Overall survival is defined as the time from enrollment to death due to any cause.	Up to approximately 36 Months
Assess Adverse Events	Assess adverse events according to the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0	12 months

Collaborators and Investigators

• Sponsor: Tongji Hospital
• Investigators: Principal Investigator: Liu Huang, Clinical Professor, Tongji Hospital , Wuhan, Hubei Province, China, 430030; Principal Investigator: Xiao Yu, Clinical Professor, Tongji Hospital , Wuhan, Hubei Province, China, 430030

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 19, 2024
• First Submitted That Met QC Criteria: May 19, 2024
• First Posted (Actual): May 23, 2024

Study Record Updates

• Last Update Posted (Actual): May 23, 2024
• Last Update Submitted That Met QC Criteria: May 19, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: UC，RCC，immunotherapy, neoadjuvant
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urologic Neoplasms
• Other Study ID Numbers: TJ-IRB20240519

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No