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Dosiseskaleringsundersøgelse af WTX-124 som monoterapi og i kombination med Pembrolizumab (Pembro) hos patienter med udvalgte avancerede eller metastatiske solide tumorer

9. november 2026 opdateret af: Werewolf Therapeutics, Inc.

Et multicenter fase I/Ib dosiseskaleringsstudie af WTX-124 som monoterapi og i kombination med Pembrolizumab hos patienter med udvalgte avancerede eller metastatiske solide tumorer

A first-in-human, Phase I, open-label, multicenter study of WTX-124 administered as monotherapy and in combination with pembrolizumab to patients with advanced or metastatic solid tumors.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

This is a first-in-human, Phase I, open-label, multicenter study designed to evaluate the safety, tolerability and preliminary efficacy of WTX-124, a conditionally-activated IL-2 prodrug, when administered as monotherapy and in combination with pembrolizumab, for the treatment of patients with advanced solid tumors. Part 1 of the study is dose escalation of WTX-124, both as monotherapy and in combination with pembrolizumab. Part 2 is dose expansion and is comprised of six arms in which WTX-124 will be administered as monotherapy and in combination with pembrolizumab to patients with advanced or metastatic cutaneous malignant melanoma or advanced or metastatic renal cell carcinoma.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

156

Fase

  • Fase 1

Kontakter og lokationer

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

Studiesteder

  • Forenede Stater
    • Arizona
      • Scottsdale, Arizona, Forenede Stater, 85258
        • HonorHealth
    • Florida
      • Tampa, Florida, Forenede Stater, 33612
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, Forenede Stater, 30322
        • Emory Winship Cancer Institute
    • Illinois
      • Chicago, Illinois, Forenede Stater, 60611
        • Northwestern University
    • Indiana
      • Indianapolis, Indiana, Forenede Stater, 46202
        • Indiana University Melvin and Bren Simon Comprehensive Cancer Center
    • Minnesota
      • Maple Grove, Minnesota, Forenede Stater, 55369
        • Minnesota Oncology Hematology, P.A.
    • New Jersey
      • Hackensack, New Jersey, Forenede Stater, 07601
        • Hackensack University Medical Center
    • New York
      • Buffalo, New York, Forenede Stater, 14203
        • Roswell Park Comprehensive Cancer Care
      • Hawthorne, New York, Forenede Stater, 10532
        • Westchester Medical Center
    • Oregon
      • Portland, Oregon, Forenede Stater, 97213
        • Providence Cancer Institute Franz Clinic
    • Texas
      • Austin, Texas, Forenede Stater, 78705-1165
        • Texas Oncology - Austin Midtown
      • Dallas, Texas, Forenede Stater, 75390-8852
        • University of Texas Southwestern Medical Center
      • Houston, Texas, Forenede Stater, 77054
        • NEXT Oncology
      • San Antonio, Texas, Forenede Stater, 78229
        • NEXT Oncology

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:

Each patient must meet all the following criteria to participate in the study:

  1. Has histological or cytological documentation of a solid tumor indication for which a CPI (e.g. anti-PD-(L)1 is indicated for all parts of the clinical study;

  2. Monotherapy Dose Escalation:

    Patients with relapsed/refractory locally advanced or metastatic solid tumors for which immunotherapy is approved, who have progressed on or are intolerant to standard therapy, including CPIs, or for whom no standard therapy with proven benefit exists.

    Combination Dose Escalation:

    Patients with relapsed/refractory locally advanced or metastatic solid tumors for which immunotherapy is approved, who have progressed on or are intolerant to standard therapy or for whom no standard therapy with proven benefit exists.

    Monotherapy Dose Expansion:

    • Arm A: Patients with relapsed advanced or metastatic RCC who have received no more than 4 prior lines of therapy in the advanced or metastatic setting
    • Arm B: Patients with relapsed advanced or metastatic cutaneous malignant melanoma who have received no more than 2 prior lines of therapy for BRAF V600 wild type and no more than 3 prior lines of therapy for BRAF V600 mutant melanoma.
    • Arm C: Patients with relapsed advanced or metastatic cSCC who have received no more than 2 prior lines of systemic therapy

    Combination Dose Expansion:

    1. Arm D: Patients with RCC who have received no more than 3 prior lines of therapy
    2. Arm E: Patients with cutaneous melanoma who may be naïve to all prior therapy for advanced or metastatic disease. For BRAF wild type melanoma, patients should have received no more than 2 prior lines of therapy. For BRAF V600 mutant disease, patients should have received no more than 3 prior lines of therapy.
    3. Arm F: Patients with PD-L1-positive NSCLC who have received no more than 3 prior lines;

  3. ≥18 years of age;

  4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;

  5. Has at least 1 measurable lesion per RECIST 1.1(lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions);

  6. Agrees to undergo a pre-treatment and on-treatment biopsy of a primary or metastatic solid tumor lesion;

  7. Has adequate organ and bone marrow function;

  8. Willingness of men and women of reproductive potential to observe highly effective birth control for the duration of treatment and for 4 months following the last dose of study drug;

  9. Additional criteria may apply

Exclusion Criteria:

  1. Have a history of another active malignancy (a second cancer) within the previous 2 years except for localized cancers that are not related to the current cancer being treated, are considered cured, and, in the opinion of the Investigator, presents a low risk of recurrence. These exceptions include, but are not limited to, basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast;
  2. Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease;
  3. Have received prior IL-2-directed therapy;
  4. Have had an allogeneic tissue/solid organ transplant;
  5. Have known symptomatic brain metastases requiring steroids;
  6. Have significant cardiovascular disease;
  7. Have an active autoimmune disease that required systemic treatment in the past 2 years;
  8. Diagnosis of immunodeficiency, is on immunosuppressive therapy, or is receiving chronic systemic or enteric steroid therapy
  9. Major surgery (excluding placement of vascular access) within 2 weeks prior to the first dose of study drug;
  10. Investigational agent or anticancer therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug;
  11. Has received prior radiotherapy within 2 weeks of start of study treatment. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease;
  12. Any unresolved toxicities from prior therapy greater than NCI CTCAE version 5.0 Grade 1 at the time of starting study drug with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy;
  13. Received a live or live-attenuated vaccine within 30 days of the first dose of study drug; Note: Administration of killed vaccines or other formats are allowed.
  14. Active, uncontrolled systemic bacterial, viral, or fungal infection;
  15. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease;
  16. Active infection as determined by hepatitis B surface antigen and hepatitis B core antibody, or hepatitis B virus DNA by quantitative polymerase chain reaction (qPCR) testing;
  17. Active infection as determined by hepatitis C virus (HCV) antibody or HCV RNA by qPCR testing;
  18. Pregnant or lactating;
  19. History of hypersensitivity to any of the study drug components;
  20. Additional criteria may apply.

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: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: WTX-124 monotherapy dose escalation

WTX-124 monotherapy dose escalation
Medicin: WTX-124

Investigation Product Monotherapy
Eksperimentel: WTX-124 in combination with pembro dose escalation

WTX-124 in combination with pembrolizumab (pembro) dose escalation
Medicin: WTX-124

Investigation Product Monotherapy

Medicin: pembrolizumab

Investigation Product in combination with approved therapy

Andre navne:
  • KEYTRUDA®
Eksperimentel: Arm A: WTX-124 monotherapy dose expansion. Patients with advanced or metastatic RCC.

Arm A: WTX-124 monotherapy dose expansion. Patients with advanced or metastatic RCC.
Medicin: WTX-124

Investigation Product Monotherapy
Eksperimentel: Arm B: WTX-124 monotherapy dose expansion. Advanced or metastatic cutaneous malignant melanoma.

Arm B: WTX-124 monotherapy dose expansion. Patients with advanced or metastatic cutaneous malignant melanoma.
Medicin: WTX-124

Investigation Product Monotherapy
Eksperimentel: Arm C: WTX-124 monotherapy dose expansion. Patients with advanced or metastatic cSCC.

Arm C: WTX-124 monotherapy dose expansion. Patients with advanced or metastatic cSCC.
Medicin: WTX-124

Investigation Product Monotherapy
Eksperimentel: Arm D: WTX-124 in combination with pembro dose expansion. Advanced or metastatic RCC.

Arm D: WTX-124 in combination with pembrolizumab dose expansion. Patients with advanced or metastatic RCC.
Medicin: WTX-124

Investigation Product Monotherapy

Medicin: pembrolizumab

Investigation Product in combination with approved therapy

Andre navne:
  • KEYTRUDA®
Eksperimentel: Arm E: WTX-124 with pembro dose expansion. Advanced or metastatic cutaneous melanoma.

Arm E: WTX-124 in combination with pembrolizumab dose expansion. Patients with advanced or metastatic cutaneous melanoma.
Medicin: WTX-124

Investigation Product Monotherapy

Medicin: pembrolizumab

Investigation Product in combination with approved therapy

Andre navne:
  • KEYTRUDA®
Eksperimentel: Arm F: WTX-124 in combination with pembro dose expansion. Advanced/metastatic PD-L1-positive NSCL

Arm F: WTX-124 in combination with pembrolizumab dose expansion. Patients with advanced or metastatic PD-L1-positive NSCLC lines.
Medicin: WTX-124

Investigation Product Monotherapy

Medicin: pembrolizumab

Investigation Product in combination with approved therapy

Andre navne:
  • KEYTRUDA®

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Forekomst af dosisbegrænsende toksiciteter (DLT'er) i monoterapi og kombinationsbehandling
Tidsramme: 4 uger
4 uger
Forekomst af behandlingsfremkomne bivirkninger i monoterapi og kombinationsterapi
Tidsramme: 24 måneder
24 måneder
Forekomst af ændringer i kliniske laboratorieabnormiteter i monoterapi og kombinationsterapi
Tidsramme: 24 måneder
24 måneder
Dosisudvidelse - forekomst af dosisbegrænsende toksiciteter (DLT'er) i monoterapi og kombinationsbehandling
Tidsramme: 4 uger
4 uger
Dosisudvidelse - Forekomst af uønskede hændelser i behandlingen ved monoterapi og kombinationsbehandling
Tidsramme: 24 måneder
24 måneder
Dosisudvidelse - Forekomst af ændringer i kliniske laboratorieabnormiteter i monoterapi og kombinationsbehandling
Tidsramme: 24 måneder
24 måneder
Dosisudvidelse - Investigator-vurderet objektiv responsrate (ORR) pr. RECIST 1.1 og iORR af iRECIST i monoterapi og kombinationsterapi
Tidsramme: 24 måneder
24 måneder

Sekundære resultatmål

Resultatmål
Tidsramme
Samlet overlevelse
Tidsramme: 36 måneder
36 måneder
Varighed af svar
Tidsramme: 24 måneder
24 måneder
Investigator-vurderet objektiv responsrate (ORR) pr. RECIST 1.1 og iORR af iRECIST i monoterapi og kombinationsterapi
Tidsramme: 24 måneder
24 måneder
Plasmakoncentrationer af WTX-124 og fri IL-2
Tidsramme: 24 måneder
24 måneder
Ændringer i cirkulerende immuncellepopulationer som reaktion på monoterapi og kombinationsterapi
Tidsramme: 24 måneder
24 måneder
Ændringer i opløselige cytokiner som reaktion på monoterapi og kombinationsterapi
Tidsramme: 24 måneder
24 måneder
Ændringer i tumorens immunprofil som reaktion på monoterapi og kombinationsterapi
Tidsramme: 24 måneder
24 måneder
Investigator-vurderet objektiv responsrate (ORR) pr. RECIST 1.1 og iORR af iRECIST i monoterapi og kombinationsterapi (ved fremskreden eller metastatisk nyrecellecarcinom og fremskreden eller metastatisk kutant malignt melanom)
Tidsramme: 24 måneder
24 måneder
Forekomst af antidrug antistof (ADA).
Tidsramme: 24 måneder
24 måneder
Progressionsfri overlevelse
Tidsramme: 24 måneder
24 måneder
At undersøge immunologiske biomarkører i perifert blod og tumor, der kan korrelere med behandlingsresultatet af WTX-124 som monoterapi eller i kombination med pembrolizumab
Tidsramme: 24 måneder
24 måneder
At vurdere tumorbiopsier for potentielle biomarkører for target-engagement og immunpathway-aktivering
Tidsramme: 24 måneder
24 måneder

Samarbejdspartnere og efterforskere

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

Sponsor

Werewolf Therapeutics, Inc.

Samarbejdspartnere

Merck Sharp & Dohme LLC

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)

15. august 2022

Primær færdiggørelse (Faktiske)

22. april 2026

Studieafslutning (Faktiske)

22. april 2026

Datoer for studieregistrering

Først indsendt

14. juli 2022

Først indsendt, der opfyldte QC-kriterier

26. juli 2022

Først opslået (Faktiske)

29. juli 2022

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

10. november 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

9. november 2026

Sidst verificeret

1. maj 2025

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • WTX-124x2101
  • MK-3475-D17 (Anden identifikator: Merck Sharp & Dohme LLC)
  • KEYNOTE-D17 (Anden identifikator: Merck Sharp & Dohme LLC)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

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