Combination of DV and Tislelizumab for Renal Preservation in High-risk UTUC Patients

Perioperative Disitamab Vedotin and Tislelizumab Followed by Nephron-Sparing Surgery in High-Risk Upper Tract Urothelial Carcinoma: A Phase 2 Trial (DISTINCT-I)

This is a prospective, open, multiple-center clinical study of renal preservation therapy in high-risk upper urinary tract urothelial carcinoma patients . The study was conducted in accordance with the Good Practice for Quality Control of Clinical Trials for Pharmaceutical Products (GCP). Approximately 20 subjects will be enrolled to evaluate the efficacy and safety of RC48 (2.0 mg/kg intravenously every 3 weeks) combined with Tislelizumab (200mg intravenously every 3 weeks).

Study Overview

• Status: Recruiting
• Conditions: Upper Urinary Tract Urothelial Carcinoma; Kidney Preservation; HER-2 ADC; PD-1antibody
• Intervention / Treatment: Drug: RC48 Combined With Tislelizumab

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

Contacts and Locations

• Study Contact: Name: jiwei huang; Phone Number: 8613651682825; Email: jiweihuang@outlook.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Ethics Committee of Shanghai Renji Hospital
      • Contact: Qi Lu; Phone Number: +86021-68383364; Email: rjllb3364@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. ECOG 0~2;
2. HER-2 IHC 0-3+;
3. Subjects underwent cystoscopic/ureteroscopic biopsy, exfoliation cytology, and CT/MRI diagnosis;
4. Patients were judged to be high-risk urothelial carcinoma of the upper urinary tract (meeting any of the following risk factors: hydronephrosis, tumor diameter ≥2cm, high-grade, multiple tumors in cytology, previous history of radical cystectomy for high-grade bladder cancer, biopsy pathology with other tissue components);
5. High-risk UTUC(excluding low-risk UTUC),including renal pelvic tumors (cT1-T3, N0) or ureteral tumors (cT1-T3, N0-N1) M0;
6. Patients with indications of absolute or relative renal protection (only kidney, renal insufficiency: eGFR < 60 ml/min)
7. Have the desire to protect the kidney;
8. There is no indication of absolute or relative kidney preservation, but patients have a strong desire to preserve kidney.
9. Has and agrees to provide cystoscopic/ureteroscopic biopsy tissue specimens and to reserve pre-treatment blood,
10. Urine and biopsied biological samples;
11. Predicted survival ≥3 months;
12. Major organ function is normal (14 days prior to enrollment)
13. International Normalized ratio (INR), activated partial thromboplastin time (aPTT) : ≤1.5× ULN (This criterion only applies to patients who are not receiving anticoagulant therapy; Patients receiving anticoagulant therapy should keep anticoagulants within therapeutic limits);
14. Did not receive systemic corticosteroid medication within 4 weeks prior to treatment;
15. Fertile men or women who are at risk of becoming pregnant must use a highly effective contraceptive method during the trial (such as oral contraceptives, intrauterine devices, controlled sexual desire or barrier contraception combined with spermicide) and continue using contraception for 12 months after the end of treatment;
16. The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with follow-up.

Exclusion Criteria:

1. Previously received anti-PD-1, anti-PD-L1, anti-PD-L2 therapy, including adjuvant therapy stage;
2. Known allergy to recombinant humanized anti-PD-1 monoclonal antibody drugs and their components;
3. Had received other antitumor therapy (including corticosteroid therapy, immunotherapy) or participated in other clinical studies within 4 weeks prior to the study treatment, or had not recovered from the previous toxicity (except for 2 degrees of hair loss and 1 degree of neurotoxicity);
4. Pregnant or lactating women;
5. Positive HIV test result;
6. People with active hepatitis B or C
7. HBsAg or HBcAb positive patients also detected HBV DNA copy number positive (quantitative detection limit is 500IU/ml, or reach the positive value of the study center); Screening studies of such patients must test for HBV DNA;
8. Patients who tested positive for HCV antibodies were enrolled in this study only if the PCR results of HCV RNA were negative.
9. A clear history of active tuberculosis;
10. Have active autoimmune diseases that have required systemic treatment within the past 2 years (e.g., with disease-regulating drugs, corticosteroids, or immunosuppressive drugs) that allow for relevant replacement therapy (e.g., thyroxine, pancreatic hormone, or physiologic corticosteroid replacement therapy for renal or pituitary insufficiency);
11. Other serious, uncontrolled concomitant diseases that may affect protocol adherence or interfere with interpretation of results, These include active opportunistic or progressive (severe) infections, uncontrolled diabetes, cardiovascular disease (heart failure of Grade Ⅲ or Ⅳ as defined by the New York Heart Association scale, heart block above grade Ⅱ, myocardial infarction within the past 6 months, unstable arrhythmia or unstable angina, cerebral infarction within 3 months, etc.) Or pulmonary disease (history of interstitial pneumonia, obstructive pulmonary disease, and symptomatic bronchospasm);
12. Received live vaccine within 4 weeks prior to the start of treatment;
13. Have previously received allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
14. Major surgical procedures (excluding diagnostic surgery) within 4 weeks prior to the start of treatment; Those who have a history of psychotropic drug abuse and cannot abstain or have a history of mental disorders;
15. A large amount of pleural effusion or ascites accompanied by clinical symptoms or requiring symptomatic treatment;
16. Have had other unhealed malignancies in the past 5 years, excluding those that are apparently cured or curable, such as basal or squamous cell skin cancer, localized low-risk prostate cancer, carcinoma in situ of the cervix or carcinoma in situ of the breast; Remarks: Patients with localized low-risk prostate cancer (defined as stage ≤T2a, Gleason score ≤6, and PSA≤10ng/mL at the time of prostate cancer diagnosis (as measured) who had received radical therapy and had no biochemical recurrence of prostate specific antigen (PSA) were eligible to participate in this study);
17. Bladder cancer (MIBC);
18. Other severe, acute, or chronic medical or psychiatric conditions or laboratory abnormalities that, according to the investigator, may increase the risks associated with study participation or may interfere with the interpretation of the study results.

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: RC48 Combined With Tislelizumab; In this trial, RC48 was scheduled to be administered at a dose of 2.0 mg/kg every 3 weeks, with the first dose on day 1 of the first cycle. Tislelizumab was administered at a dose of 200 mg every 3 weeks, with the first dose on day 1 of the first 21-day cycle. The drug is diluted with normal saline and administered by intravenous drip for one hour.	Drug: RC48 Combined With Tislelizumab; In this trial, RC48 was scheduled to be administered at a dose of 2.0 mg/kg every 3 weeks, with the first dose on day 1 of the first cycle. Tislelizumab was administered at a dose of 200 mg every 3 weeks, with the first dose on day 1 of the first 21-day cycle. The drug is diluted with normal saline and administered by intravenous drip for one hour.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
kidney-intact event-free survival (KI-EFS)	the time from enrollment to any event, including high-risk UTUC local recurrence(tumor size ≥2 cm, local invasion on CT or MRI, hydronephrosis, or multifocality), distant metastasis, death from any cause, or conversion to RNU	up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the proportion of RUN	The proportion of patients undergoing radical surgery for UTUC (upper tract urothelial carcinoma) after enrollment.	up to 2 year
clinical complete response	The rate of CCR is defined by negative ureteroscope, urine cytology, and negative imaging	3 month before surgery
clinical complete response	The rate of CCR is defined by negative ureteroscope, urine cytology, and negative imaging	4 month after surgery
disease-free survival	the time from enrollment to any disease recurrence (excluding isolated bladder recurrence) or death from any cause	up to 2 year
the proportion of adverse events	adverse events graded according to CTCAE version 5.0	up to 2 year
renal function preservation	the change in eGFR from baseline to 1 year	up to 1 year

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Collaborators: Peking University First Hospital; West China Hospital; Tianjin Medical University Second Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2023
• Primary Completion (Actual): November 3, 2025
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: June 11, 2023
• First Submitted That Met QC Criteria: June 20, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; tislelizumab
• Other Study ID Numbers: DISTINCT-I

Drug and device information, study documents

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