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

7 mai 2026 mis à jour par: 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.

Aperçu de l'étude

Statut

Pas encore de recrutement

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Estimé)

50

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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
Médicament: 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.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Kidney-Intact Event-Free Survival (KI-EFS) at 1 year
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Kidney-Intact Event-Free Survival at 2 years
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: Up to 12 months
Change in estimated glomerular filtration rate (eGFR)
Up to 12 months
Safety and Tolerability
Délai: Up to 90 days post-treatment
Incidence of treatment-related adverse events graded by CTCAE v5.0
Up to 90 days post-treatment

Autres mesures de résultats

Mesure des résultats
Description de la mesure
Délai
ctDNA/utDNA Dynamics
Délai: 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
Délai: baseline, pre-Induction Therapy
HER2 expression level pre-Induction Therapy
baseline, pre-Induction Therapy

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

RenJi Hospital

Collaborateurs

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

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

31 mai 2026

Achèvement primaire (Estimé)

31 décembre 2027

Achèvement de l'étude (Estimé)

31 décembre 2028

Dates d'inscription aux études

Première soumission

4 mai 2026

Première soumission répondant aux critères de contrôle qualité

7 mai 2026

Première publication (Réel)

13 mai 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

13 mai 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

7 mai 2026

Dernière vérification

1 mai 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • DISTINCT II

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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