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En første-i-human undersøgelse af YL217 hos patienter med avancerede faste tumorer

15. september 2026 opdateret af: MediLink Therapeutics (Suzhou) Co., Ltd.

En fase 1, multicenter, open-label, første-i-human undersøgelse for at evaluere sikkerheden, tolerabiliteten, farmakokinetikken og effektiviteten af ​​YL217 hos patienter med avancerede faste tumorer

A Phase 1 First-in-Human study of YL217 in Patients with Advanced Solid Tumors

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

YL217 is an antibody-drug conjugate (ADC) that targets CDH17 (Cadherin-17) protein and is being developed for the treatment of cancer. YL217 is comprised of three components: 1) YL217-mAb, a CDH17-targeting recombinant humanized immunoglobulin G1 (IgG1) monoclonal antibody, 2) YL0010014, a topoisomerase I inhibitor, and 3) an enzymatically cleavable methylsulfonyl pyrimidine tripeptide drug linker.

The in vivo anti-tumor efficacy of YL217 was evaluated in immune-deficient mice bearing human colorectal cancer, gastric cancer and patient derived colorectal cancer xenograft tumors. The results indicated that YL217 was well tolerated, and YL217 suppressed growth of established human tumors in a dose-dependent manner in cancer cells or patient derived xenograft models.

Therefore, in order to meet the huge unmet medical needs in the field of gastrointestinal cancer treatment, it is planned to conduct the first human phase I clinical study of YL217 in patients with advanced solid tumors.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

630

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

    • Arizona
      • Phoenix, Arizona, Forenede Stater, 85054
        • Rekruttering
        • Mayo Clinic Arizona
        • Kontakt:
          • Study Coordinator
    • California
      • Santa Monica, California, Forenede Stater, 90404
        • Rekruttering
        • UCLA Hematology/Oncology - Santa Monica
        • Kontakt:
          • Study Coordinator
    • Connecticut
      • New Haven, Connecticut, Forenede Stater, 06519
        • Rekruttering
        • Yale Cancer Center
    • Kansas
      • Kansas City, Kansas, Forenede Stater, 66205
        • Rekruttering
        • The University of Kansas Cancer Center (KUCC)
        • Kontakt:
          • Study Coordinator
    • Michigan
      • Detroit, Michigan, Forenede Stater, 48201
        • Rekruttering
        • Karmanos Cancer Institute
        • Kontakt:
          • Study Coordinator
    • New York
      • New York, New York, Forenede Stater, 10032
        • Rekruttering
        • Columbia University Irving Medical Center
        • Kontakt:
          • Study Coordinator
    • North Carolina
      • Durham, North Carolina, Forenede Stater, 27710
        • Rekruttering
        • Duke University Medical Center (DUMC)
        • Kontakt:
          • Study Coordinator
    • Ohio
      • Cincinnati, Ohio, Forenede Stater, 45219
        • Rekruttering
        • University of Cincinnati Medical Center
        • Kontakt:
          • Study Coordinator
      • Cleveland, Ohio, Forenede Stater, 44195
        • Rekruttering
        • Cleveland Clinic Taussig Cancer Institute
        • Kontakt:
          • Study Coordinator
    • Texas
      • Houston, Texas, Forenede Stater, 77030
        • Rekruttering
        • The University of Texas MD Anderson Cancer Center
        • Kontakt:
          • Study Coordinator
      • San Antonio, Texas, Forenede Stater, 78229
        • Rekruttering
        • UT Health San Antonio - Mays Cancer Center
        • Kontakt:
          • Study Coordinator
    • Wisconsin
      • Madison, Wisconsin, Forenede Stater, 53792
        • Rekruttering
        • University of Wisconsin Health - UW Carbone Cancer Center
        • Kontakt:
          • Study Coordinator
    • Bejing
      • Beijing, Bejing, Kina, 100730
        • Rekruttering
        • Peking Union Medical College Hospital
        • Kontakt:
          • Study Coordinator
    • Guangdong
      • Guangzhou, Guangdong, Kina, 510655
        • Ikke rekrutterer endnu
        • The Sixth Affiliated Hospital of Sun Yat-sen University
    • Heilongjiang
      • Harbin, Heilongjiang, Kina, 150081
        • Rekruttering
        • Harbin Medical University Cancer Hospital
        • Kontakt:
          • Study Coordinator
    • Jiangxi
      • Nanchang, Jiangxi, Kina, 330006
        • Ikke rekrutterer endnu
        • The First Affiliated Hospital of Nanchang University
    • Liaoning
      • Shenyang, Liaoning, Kina, 110001
        • Ikke rekrutterer endnu
        • The First Affiliated Hospital of China Medical University
    • Shandong
      • Jinan, Shandong, Kina, 250117
        • Rekruttering
        • Cancer Hospital of Shandong First Medical University
        • Kontakt:
          • Study Coordinator
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, Kina, 200025
        • Rekruttering
        • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
        • Kontakt:
          • Study Coordinator
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, Kina, 300060
        • Rekruttering
        • Tianjin Medical University Cancer Institute & Hospital
        • Kontakt:
          • Study Coordinator
    • Zhejiang
      • Hangzhou, Zhejiang, Kina, 310022
        • Rekruttering
        • Zhejiang Cancer Hospital
        • Kontakt:
          • Study Coordinator

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • Informed of the study before the start of the study and voluntarily sign their name and date in the ICF
  • Able and willing to comply with protocol visits and procedures
  • Age≥ 18 years
  • ECOG PS of 0 or 1
  • Pathologically confirmed diagnosis of an advanced solid tumor. For CRC cohorts: : Histologically or cytologically documented locally advanced unresectable or metastatic colorectal carcinoma that is not eligible for curative surgery and/or definitive chemoradiotherapy
  • Adequate organ and bone marrow function.
  • Have at least 1 extracranial measurable tumor lesion.
  • Adequate archival formalin-fixed paraffin embedded (FFPE) tissue from prior biopsy.

Exclusion Criteria:

  • Prior treatment with an agent targeting CDH17
  • Prior discontinuation of a topoisomerase I inhibitor due to treatment-related toxicities.
  • Have received an ADC consisting of a topoisomerase I inhibitor.
  • Concurrent enrollment in another clinical study, unless it is an observational clinical study.
  • Inadequate washout period for prior anticancer treatment before the first dose of study drug
  • Undergone major surgery within 4 weeks before the first dose of study drug or expect major surgery during the study, minor procedures (e.g., core needle biopsy, superficial biopsy) within 7 days before the first dose of study drug.
  • Received long term systemic steroids or other immunosuppressive therapy within 2 weeks before the first dose of study drug.
  • Received any live vaccine within 4 weeks before the first dose of study drug or intend to receive a live vaccine during the study.
  • Diagnosis or evidence of spinal cord compression or leptomeningeal carcinomatosis.
  • Uncontrolled or clinically significant cardiovascular and cerebrovascular diseases.
  • A history of non-infectious interstitial lung disease (ILD)/pneumonitis that requires steroids, current active ILD/pneumonitis.
  • Have clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
  • Uncontrolled third-space fluid that requires repeated drainage.
  • Digestive system disease that may cause bleeding, perforation, jaundice, fistula, GI obstruction within 6 months prior to the first dose of study drug administration or have active inflammatory bowel disease.
  • An active tuberculosis based on medical history.
  • Known human immunodeficiency virus (HIV) infection.
  • Active hepatitis C infection.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Sekventiel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Combo-Dose Escalation,Backfill and Expansion

Participants will receive YL217 in combination of bevacizumab with or without 5-FU/LV

Patients will receive specific dose of YL217 administered via intravenous(IV)infusion.

Participants will receive bevacizumab administered via intravenous(IV) infusion,at 5mg/kg,Q2W.

Participants will receive 5 fluorouracil 2400mg/m2 and leucovorin 400mg/m2, administered via intravenous (IV) infusion, Q2W

Eksperimentel: Mono-Dose Escalation,Backfill and Expansion

Participants will receive YL217 monotherapy

Patients will receive specific dose of YL217 administered via intravenous(IV)infusion.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Nature and frequency of dose-limiting toxicity(DLT)
Tidsramme: Up to approximately 3 years

The purpose of DLT is to find maximum tolerated dose (MTD).

Up to approximately 3 years
Nature and frequency of adverse events (AEs) with severity
Tidsramme: Up to approximately 3 years

Nature and frequency of AEs with severity is aim to evaluate the safety of YL217.

Up to approximately 3 years
objective response rate (ORR)
Tidsramme: Up to approximately 3 years

ORR: defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR).

Up to approximately 3 years

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
For at evaluere sikkerhedsdepunktet for perifer iltmætning (SPO2)
Tidsramme: Op til cirka 3 år
Op til cirka 3 år
Eastern Cooperative Oncology Group performance status (ECOG PS)
Tidsramme: Up to approximately 3 years

Deterioration of Eastern Cooperative Oncology Group performance status (ECOG PS)

Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter AUC
Tidsramme: Up to approximately 3 years

The area under curve: AUC is the total amount of YL217 in bloodstream after drug administration.

Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter Cmax
Tidsramme: Up to approximately 3 years

Maximum concentration:The highest measured concentration of YL217 in the bloodstream.

Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter Ctrough
Tidsramme: Up to approximately 3 years

Trough concentration

Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter Tmax
Tidsramme: Up to approximately 3 years

Time to maximum observed concentration

Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter CL
Tidsramme: Up to approximately 3 years

Clearance: defined as the amount of drug removed from the bloodstream by the body per unit of time.

Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter Vd
Tidsramme: Up to approximately 3 years

volume of distribution

Up to approximately 3 years
Characterize Pharmacokinetics(PK) parameter t1/2
Tidsramme: Up to approximately 3 years

Half-life time:defined as the time it takes for the concentration of the drug in plasma or serum to be reduced by 50%.

Up to approximately 3 years
Immunogenicity endpoint: Incidence of anti-YL217 antibody (ADAs).
Tidsramme: Up to approximately 3 years

The presence of ADAs in patients treated with YL217 will be assessed to evaluate immunogenicity.

Up to approximately 3 years
Disease control rate (DCR)
Tidsramme: Up to approximately 3 years

DCR: defined as the proportion of patients who achieved a best overall response of complete response (CR), partial response (PR) or stable disease (SD).

Up to approximately 3 years
Duration of response (DoR)
Tidsramme: Up to approximately 3 years

DoR: defined as the time interval from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of progressive disease (PD).

Up to approximately 3 years
Time to response (TTR)
Tidsramme: Up to approximately 3 years

TTR: defined as the time interval from the date of the first dose of study drug to the date of the first documentation of objective response (CR or PR).

Up to approximately 3 years
Depth of response (DpR)
Tidsramme: Up to approximately 3 years

DpR: defined as the proportion of target lesion shrinkage from baseline to maximum tumor size.

Up to approximately 3 years
Progression-free survival (PFS)
Tidsramme: Up to approximately 3 years

PFS: defined as the time interval from the date of the first dose of study drug to the date of first documentation of PD or death due to any cause, whichever occurs first.

Up to approximately 3 years
Overall survival (OS)
Tidsramme: Up to approximately 3 years

OS: defined as the time interval from the date of the first dose of study drug to the date of death due to any cause.

Up to approximately 3 years

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

2. juli 2025

Primær færdiggørelse (Anslået)

1. juli 2028

Studieafslutning (Anslået)

1. juli 2030

Datoer for studieregistrering

Først indsendt

18. februar 2025

Først indsendt, der opfyldte QC-kriterier

4. marts 2025

Først opslået (Faktiske)

5. marts 2025

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

18. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

15. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Andre undersøgelses-id-numre

  • YL217-INT-101-01

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

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Ja

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Ingen

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