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Biomarker-Enriched Kidney-Preserving Strategy With Disitamab Vedotin Plus Tislelizumab in HER2-Positive High-Risk Upper Tract Urothelial Carcinoma

7 mei 2026 bijgewerkt door: RenJi Hospital

A Prospective, Multicentre, Single-Arm Phase II Study Evaluating a Response-Adapted Kidney-Preserving Strategy Using Neoadjuvant Disitamab Vedotin Plus Tislelizumab in Patients With HER2-Positive High-Risk Upper Tract Urothelial Carcinoma (DISTINCT-II)

This is a prospective, multicentre, single-arm phase II study evaluating a response-adapted kidney-preserving strategy in patients with HER2-positive high-risk upper tract urothelial carcinoma (UTUC). Patients will receive neoadjuvant disitamab vedotin plus tislelizumab, followed by response-adapted local treatment, including kidney-sparing surgery or radical nephroureterectomy based on predefined criteria.

The primary objective is to assess whether this multimodal strategy can achieve clinically meaningful oncologic control while preserving renal function, as measured by 1-year kidney-intact event-free survival (KI-EFS). Secondary and exploratory objectives include evaluation of clinical response, survival outcomes, safety, renal function preservation, and longitudinal dynamics of circulating and urinary tumor DNA.

Studie Overzicht

Toestand

Nog niet aan het werven

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

This is a prospective, multicentre, single-arm, phase II clinical trial designed to evaluate the efficacy and safety of a response-adapted kidney-preserving treatment strategy in patients with HER2-positive high-risk upper tract urothelial carcinoma (UTUC).

Eligible patients will receive neoadjuvant systemic therapy consisting of disitamab vedotin in combination with tislelizumab administered every 3 weeks for 2-4 cycles. Tumour response will be assessed after two cycles using radiographic evaluation and clinical assessment. Patients demonstrating clinical benefit will proceed to complete induction therapy, followed by comprehensive restaging including imaging, ureteroscopy with biopsy, and urine cytology.

Subsequent local treatment will be determined according to a predefined response-adapted algorithm. Patients meeting protocol-specified criteria will undergo kidney-sparing surgery (KSS), including segmental ureterectomy or endoscopic ablation depending on tumour location and anatomical feasibility. Patients not meeting criteria for KSS will undergo radical nephroureterectomy (RNU).

The primary objective of the study is to determine whether this multimodal strategy can achieve clinically meaningful oncologic control while preserving renal function in a biomarker-selected population.

In addition, longitudinal biospecimen collection will be conducted to evaluate the dynamics of urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) as exploratory biomarkers of treatment response and minimal residual disease.

Studietype

Ingrijpend

Inschrijving (Geschat)

50

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Locaties

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China
        • Ethics Committee of Shanghai Renji Hospital
        • Contact:

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

Inclusion Criteria:

  • Age ≥18 years at the time of informed consent.
  • Histologically confirmed upper tract urothelial carcinoma (UTUC) arising from the renal pelvis or ureter, based on ureteroscopic biopsy.
  • High-risk UTUC, defined by at least one of the following features: Tumour size ≥2 cm; High-grade cytology or biopsy; Radiographic evidence of local invasion (≥cT2); Hydronephrosis; Multifocal disease
  • Clinical stage cT1-T3, N0-N1, M0, based on radiographic assessment.
  • N1 disease is permitted only if lymph nodes are considered resectable.
  • HER2-positive disease, defined as immunohistochemistry (IHC) score of 1+，2+ or 3+ on tumour tissue, assessed according to predefined criteria.
  • At least one measurable lesion according to RECIST version 1.1.
  • ECOG performance status of 0-1
  • Adequate organ function, including: Hematologic function; Hepatic function; Renal function (no strict upper/lower limit required);
  • Patients must be considered potential candidates for a kidney-preserving treatment strategy, including: Absolute or relative indication for renal preservation (e.g., solitary kidney, baseline renal insufficiency), or Strong preference for kidney preservation after multidisciplinary discussion
  • Ability to understand and willingness to sign written informed consent.

Exclusion Criteria:

  • Evidence of distant metastatic disease (M1).
  • Unresectable or bulky nodal disease (≥N2) not amenable to curative-intent surgery.
  • Prior systemic therapy for urothelial carcinoma, including:Chemotherapy; Immunotherapy; HER2-targeted therapy.
  • Prior radical nephroureterectomy for current disease.
  • Active autoimmune disease requiring systemic treatment within the past 2 years.
  • Current use of immunosuppressive medication, excluding physiologic doses of corticosteroids.
  • Uncontrolled intercurrent illness, including but not limited to: Active infection requiring systemic therapy; Uncontrolled cardiovascular disease; Significant pulmonary disease
  • Known active hepatitis B, hepatitis C, or HIV infection with uncontrolled viral replication.
  • History of another malignancy within the past 5 years, except: Adequately treated basal cell carcinoma; Squamous cell skin cancer; In situ carcinoma.
  • Pregnant or breastfeeding women.
  • Any condition that, in the opinion of the investigator, would interfere with study participation or interpretation of results.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Neoadjuvant disitamab vedotin + tislelizumab followed by response-adapted surgery

Drug: Disitamab Vedotin Administered intravenously at 2.0 mg/kg every 3 weeks

Drug: Tislelizumab Administered intravenously at 200 mg every 3 weeks

Procedure: Surgery Kidney-sparing surgery (segmental ureterectomy or endoscopic ablation) or radical nephroureterectomy based on predefined criteria
Geneesmiddel: 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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Kidney-Intact Event-Free Survival (KI-EFS) at 1 year
Tijdsspanne: From enrollment to 12 months

KI-EFS is defined as the time from study enrollment to the first occurrence of any of the following events:

High-risk recurrence of upper tract urothelial carcinoma (local, regional, or distant), defined according to prespecified clinical or radiographic criteria Death from any cause Conversion to radical nephroureterectomy (RNU) for any reason

Patients without an event will be censored at the date of last disease assessment.
From enrollment to 12 months

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Kidney-Intact Event-Free Survival at 2 years
Tijdsspanne: Up to 24 months

KI-EFS is defined as the time from study enrollment to the first occurrence of any of the following events:

High-risk recurrence of upper tract urothelial carcinoma (local, regional, or distant), defined according to prespecified clinical or radiographic criteria Death from any cause Conversion to radical nephroureterectomy (RNU) for any reason

Patients without an event will be censored at the date of last disease assessment.
Up to 24 months
Disease-Free Survival (DFS) Renal Function Preservation
Tijdsspanne: Up to 24 months
Time from definitive local treatment (KSS or RNU) to upper tract recurrence or death from any cause. Isolated bladder recurrence will not be counted as an event.
Up to 24 months
Clinical Complete Response (cCR) Rate After Induction Therapy
Tijdsspanne: Immediately after Induction Therapy
Clinical complete response (cCR) was defined as concordant negative findings on cross-sectional imaging, ureteroscopy, urine cytology, and targeted biopsy according to predefined criteria
Immediately after Induction Therapy
Clinical Complete Response (cCR) Rate After Kidney-Sparing Surgery
Tijdsspanne: 1 month after surgery
Clinical complete response (cCR) was defined as concordant negative findings on cross-sectional imaging, ureteroscopy, urine cytology, and targeted biopsy according to predefined criteria
1 month after surgery
Renal Function Preservation
Tijdsspanne: Up to 12 months
Change in estimated glomerular filtration rate (eGFR)
Up to 12 months
Safety and Tolerability
Tijdsspanne: Up to 90 days post-treatment
Incidence of treatment-related adverse events graded by CTCAE v5.0
Up to 90 days post-treatment

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
ctDNA/utDNA Dynamics
Tijdsspanne: Up to 12 months
Detection tumor DNA (ctDNA/utDNA) using a fixed deep-sequencing panel.
Up to 12 months
HER2 expression level Exploratory Molecular Analyses
Tijdsspanne: baseline, pre-Induction Therapy
HER2 expression level pre-Induction Therapy
baseline, pre-Induction Therapy

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

RenJi Hospital

Medewerkers

Peking University First Hospital
West China Hospital
Tianjin Medical University Second Hospital

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Geschat)

31 mei 2026

Primaire voltooiing (Geschat)

31 december 2027

Studie voltooiing (Geschat)

31 december 2028

Studieregistratiedata

Eerst ingediend

4 mei 2026

Eerst ingediend dat voldeed aan de QC-criteria

7 mei 2026

Eerst geplaatst (Werkelijk)

13 mei 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

13 mei 2026

Laatste update ingediend die voldeed aan QC-criteria

7 mei 2026

Laatst geverifieerd

1 mei 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • DISTINCT II

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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