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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 oppdatert av: 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.

Studieoversikt

Status

Har ikke rekruttert ennå

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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

Intervensjonell

Registrering (Antatt)

50

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studiesteder

  • Kina
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, Kina
        • Ethics Committee of Shanghai Renji Hospital
        • Ta kontakt med:

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Voksen
  • Eldre voksen

Tar imot friske frivillige

Nei

Beskrivelse

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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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
Legemiddel: 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.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Kidney-Intact Event-Free Survival (KI-EFS) at 1 year
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Kidney-Intact Event-Free Survival at 2 years
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: Up to 12 months
Change in estimated glomerular filtration rate (eGFR)
Up to 12 months
Safety and Tolerability
Tidsramme: Up to 90 days post-treatment
Incidence of treatment-related adverse events graded by CTCAE v5.0
Up to 90 days post-treatment

Andre resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
ctDNA/utDNA Dynamics
Tidsramme: 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
Tidsramme: baseline, pre-Induction Therapy
HER2 expression level pre-Induction Therapy
baseline, pre-Induction Therapy

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

RenJi Hospital

Samarbeidspartnere

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

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Antatt)

31. mai 2026

Primær fullføring (Antatt)

31. desember 2027

Studiet fullført (Antatt)

31. desember 2028

Datoer for studieregistrering

Først innsendt

4. mai 2026

Først innsendt som oppfylte QC-kriteriene

7. mai 2026

Først lagt ut (Faktiske)

13. mai 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

13. mai 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

7. mai 2026

Sist bekreftet

1. mai 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • DISTINCT II

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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