DV Combined With Toripalimab for Renal Preservation in Solitary Kidney or Renal Insufficiency or Bilateral Multiple UTUC

A Prospective, Open-label, Single-arm, Clinical Study of Disitamab Vedotin Combined With Toripalimab for Renal Preservation in Solitary Kidney or Renal Insufficiency or Bilateral Multiple Upper Urinary Tract Urothelial Carcinoma

Approximately 20 participants will be enrolled in the study to evaluate the efficacy and safety of the combination of DV (DV, 2.0 mg/kg, intravenously administered every 2 weeks) and toripalimab (toripalimab, 3.0mg/kg, intravenously administered every 2 weeks). Subjects will receive 6 cycles of DV and toripalimab, followed by laser surgery to remove ureteral or renal pelvis tumors, followed by 12 cycles of DV and 1 year of toripalimab consolidation therapy. Efficacy and safety were evaluated by cystoscopy, ureteroscopy, laboratory tests, and imaging examinations after treatment.

Study Overview

• Status: Recruiting
• Conditions: Renal Insufficiency; Solitary Kidney; Upper Urinary Tract Urothelial Carcinoma
• Intervention / Treatment: Drug: DV; Drug: Toripalimab; Procedure: Laser surgery

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dingwei Ye, Doctor; Phone Number: 64175590-82800; Email: dwyeli@163.com
• Study Contact Backup: Name: Hailiang Zhang, Doctor; Phone Number: 64175590-82800; Email: zhanghl918@163.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: dingwei ye; Phone Number: 64175590-82800

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• ≥18 years old;
• Histologically confirmed isolated renal or renal insufficiency or bilateral upper urinary tract urothelial carcinoma;
• Refusal or ineligibility for RNU;

• Preoperative risk stratification was defined as high-risk UTUC, defined as patients with any of the following factors:

  1. Hydronephrosis;
  2. Tumor diameter ≥2cm;
  3. Urine cytology suggests a high-grade tumor;
  4. A ureteroscopic biopsy suggests a high-grade tumor;
  5. CT showed a localized invasion;
  6. Multifoci diseases;
  7. With multiple histological subtypes;
• ECOG 0~1;

• Major organ function is normal (14 days prior to enrollment) if the following criteria are met:

  1. The blood routine examination criteria should meet (no blood transfusion and no granulocyte colony stimulation agent treatment within 14 days before enrollment): HB≥90 g/L; ANC≥1.5×109 /L; PLT≥100×109 /L;
  2. Non-functional organic diseases shall meet the following criteria: T-BIL≤1.5×ULN (upper limit of normal value); ALT and AST≤2.5 x ULN; Serum creatinine ≤2×ULN, or endogenous creatinine clearance ≥ 30ml/min(Cockcroft-Gault formula);
• Subjects (or their legal representatives) must sign an informed consent form (ICF) indicating that they understand the purpose and procedures of the study and are willing to participate in the study.
• Pregnant women must have a negative pregnancy test result (beta-hCG) (urine or serum) within 7 days before the first administration of the randomized or study drug.

Exclusion Criteria:

• Histopathological examination revealed any small cell component of ureter or pelvis, simple adenocarcinoma, simple squamous cell carcinoma, or simple squamous CIS;
• Previous treatment with other PD-1/PD-L1 inhibitors and/or HER-2 inhibitors;
• Active malignancies other than the disease being studied for treatment (i.e., disease progression within the last 24 months or requiring a change in treatment), only the following special cases are allowed: i. Skin cancer that has been treated within the last 24 months and has been completely cured ii. Adequately treated lobular carcinoma in situ (LCIS) and ductus CIS iii. History of local breast cancer and is receiving antihormonal drugs or history of local prostate cancer (N0M0) and is receiving androgen blocking therapy;
• History of uncontrolled cardiovascular disease, including: 1) any of the following in the past 3 months: unstable angina pectoris, myocardial infarction, ventricular fibrillation, torsion ventricular tachycardia, cardiac arrest, or known congestive New York Heart Association Class III-IV heart failure, cerebrovascular accident, or transient ischemic attack; 2) QTc interval prolongation confirmed by ECG evaluation at screening (Fridericia; QTc > 480 ms); 3) Pulmonary embolism or other venous thromboembolism within the past 2 months;
• Pregnant or lactating women;
• Human immunodeficiency virus (HIV) infection is known unless the subject has been on stable antiretroviral therapy for the past 6 months or longer, has not developed an opportunistic infection in the past 6 months, and has a CD4 count > 350 in the past 6 months.
• Known history of clinically significant liver disease, including viral hepatitis [active HBV infection, i.e., HBV DNA positive (>1×104 copies /mL or >2000 IU/ml) must be excluded for known hepatitis B virus (HBV) carriers; Known hepatitis C virus infection (HCV) and HCV RNA positive (>1×103 copies /mL), or other hepatitis, cirrhosis];
• Have not recovered from the toxic effects of previous anticancer treatment (except for those that are not clinically significant, such as hair loss, skin discoloration, neuropathy, and hearing impairment);
• Delayed wound healing, defined as skin/bedsore ulcers, chronic leg ulcers, known stomach ulcers, or non-healing of incisions;
• Major surgery within 4 weeks before day 1 of Cycle 1 (TURBT is not considered a major surgery);
• Other patients assessed by the investigator as unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DV+Toripalimab; DV, 2.0 mg/kg, intravenously administered every 2 weeks; toripalimab, 3.0mg/kg, intravenously administered every 2 weeks;	Drug: DV; 2.0 mg/kg, intravenously administered every 2 weeks; Other Names: RC48; Drug: Toripalimab; 3.0mg/kg, intravenously administered every 2 weeks; Other Names: JS001; Procedure: Laser surgery; Subjects will receive 6 cycles of DV and toripalimab, followed by laser surgery to remove ureteral or renal pelvis tumors, followed by 12 cycles of DV and 1 year of toripalimab consolidation therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kidney-intact disease-free survival, KI-DFS	Defined as the time to systemic relapse or death.	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression, TTP	Defined as the time to systemic progression or death.	Up to 3 years
Time to RNU	Defined by time from day of first treatment to RNU.	Up to 3 years
Disease-specific survival time, DSS	Defined by time from day of first treatment to death due to a specific disease, reflecting the clinical benefit of a specific disease.	Up to 3 years
Overall survival	Defined by time from day of first treatment to death.	Up to 3 years
3m complete remission	CR is defined by CT urography	Up to 3 years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Dingwei Ye, Doctor, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: April 3, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Neoplasms, Glandular and Epithelial; Urogenital Abnormalities; Pathological Conditions, Anatomical; Ureteral Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Neoplasms; Carcinoma; Renal Insufficiency; Carcinoma, Transitional Cell; Ureteral Neoplasms; Solitary Kidney
• Other Study ID Numbers: RC48-C012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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