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IKS014 i avancerede solide tumorer, der udtrykker HER2

23. september 2026 opdateret af: Iksuda Therapeutics Ltd.

Et fase 1-dosiseskaleringsforsøg til bestemmelse af sikkerhed, tolerance, maksimal tolereret dosis og foreløbig antineoplastisk aktivitet af IKS014, et HER2-målrettet antistoflægemiddelkonjugat (ADC), hos deltagere med avancerede HER2+ solide tumorer

This study will evaluate the recommended dose for further clinical development, safety, tolerability, anti-tumor activity, immunogenicity, pharmacokinetics and pharmacodynamics of IKS014, a HER2 targeting antibody-drug conjugate, in patients with advanced solid tumors.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

The study will consist of 2 parts: dose-escalation (Part 1) and dose-expansion (Part 2). The dose-escalation part (Part 1) of the study is to evaluate the safety and tolerability of increasing dose levels of IKS014 to establish a recommended phase 2 dose (RP2D); and the dose-expansion part (Part 2) of the study is to further evaluate the safety, pharmacokinetics/pharmacodynamics, and efficacy of IKS014 at the RP2D.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

165

Fase

  • Fase 1

Kontakter og lokationer

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

Studiekontakt

Studiesteder

    • New South Wales
      • Concord, New South Wales, Australien, 2139
        • Rekruttering
        • Concord Repatriation General Hospital Medical Oncology Clinical Trials Unit
        • Ledende efterforsker:
          • Tam Bui, MD
      • Sydney, New South Wales, Australien, 2109
        • Rekruttering
        • Macquarie University
        • Ledende efterforsker:
          • Dhanusha Sabanathan, MD
      • Westmead, New South Wales, Australien, 2145
        • Rekruttering
        • Westmead Hospital
        • Ledende efterforsker:
          • Adnan Nagrial, MD
    • Victoria
      • Frankston, Victoria, Australien, 3199
        • Rekruttering
        • Peninsula & South Eastern Haematology and Oncology Group (PSEHOG)
        • Ledende efterforsker:
          • Vinod Ganju, MD
      • Melbourne, Victoria, Australien, 3004
        • Rekruttering
        • Alfred Health
        • Ledende efterforsker:
          • Malaka Ameratunga, MD
    • Western Australia
      • Nedlands, Western Australia, Australien, 6009
        • Rekruttering
        • Linear Clinical Research
        • Ledende efterforsker:
          • Peter Lau, MD
    • California
      • Newport Beach, California, Forenede Stater, 92663
        • Rekruttering
        • Hoag Memorial Hospital Presbyterian
        • Ledende efterforsker:
          • Monica Mita, MD
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater, 02215
        • Rekruttering
        • Dana Farber Cancer Institute
        • Ledende efterforsker:
          • Nancy Lin, MD
    • Tennessee
      • Nashville, Tennessee, Forenede Stater, 37203
        • Rekruttering
        • Tennessee Oncology
        • Ledende efterforsker:
          • Jeffrey Russell, MD
    • Texas
      • Fort Worth, Texas, Forenede Stater, 76104
        • Rekruttering
        • START Dallas - Fort Worth
        • Ledende efterforsker:
          • Henry Xiong, MD
        • Kontakt:
      • Auckland, New Zealand
        • Rekruttering
        • Auckland City Hospital
        • Ledende efterforsker:
          • Jane So, MBChB
      • Singapore, Singapore
        • Rekruttering
        • National Cancer Centre Singapore
        • Ledende efterforsker:
          • Jing Ying Tira Tan, MBBS
      • Singapore, Singapore
        • Rekruttering
        • Tan Tock Seng Hospital
        • Ledende efterforsker:
          • Yue Ming Valerie Heong, MBBS

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

Key Inclusion Criteria:

  • HER2 positive solid tumors with expression defined as IHC3+, IHC2+/ISH+, or low HER2 expression defined as IHC2+ (ISH-) or IHC1+ (ISH- /+ or untested).

  • Participants with HR positive BC must have received prior treatment with a CDK4/6 inhibitor, in countries where this is standard therapy.

  • Platelets ≥ 75,000 /mcL

  • Hemoglobin ≥ 9.0 g/dL

  • Absolute neutrophil count ≥ 1000/mcL

  • No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 2 weeks prior to first study drug administration

  • Creatinine clearance > 45/mL/min (using the Cockcroft-Gault equation)

  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3 x institutional upper limit of normal (ULN) ≤ 5 x ULN if liver metastases present

  • Total bilirubin ≤ 1.5 x ULN if no liver metastases or < 3 x ULN with Gilbert's Syndrome or liver metastases at baseline

  • Albumin > 2.5 g/dL

  • Prothrombin time or international normalized ratio (INR) and either partial thromboplastin time (PTT) or activated (a) PTT ≤ 1.5 x ULN, ≤ 3 x institutional ULN if anticoagulated.

  • Must have adequate treatment washout period before trial treatment, defined as: Major surgery (≥ 4 weeks) and radiation therapy (≥ 3 weeks; in case of palliative radiation ≥ 2 weeks)

  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (or equivalent Karnofsky PS)

  • Part 2 Dose Expansion Cohorts May Include:

    1. Advanced or metastatic BC that is confirmed HER2-positive defined as IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH, as per ASCO-CAP and previously treated with at least two HER2 directed treatments.
    2. Advanced or metastatic BC that has low HER2 expression defined as IHC2+ (ISH-) or IHC1+ (ISH-/+ or untested) and previously treated with at least 1 prior line of therapy which may include chemotherapy and/or a HER2 directed ADC.
    3. Advanced or metastatic GC or GEJ cancer that is confirmed HER2-positive defined as IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH as per ASCO-CAP and previously treated with at least 1 prior line of therapy, which may include chemotherapy and/or a HER2 directed ADC.
    4. Advanced or metastatic solid tumor that has been treated with standard of care therapy and is HER2 positive (HER2 IHC3+) as per ASCO-CAP or metastatic NSCLC (that has been treated with standard of care therapy) with a known activating HER2 (ERBB2) mutation.
    5. Advanced or metastatic adenocarcinoma of the Esophagus that has been treated with at least one prior line of standard treatment, which may have included a HER2-directed therapy. The tumor must be HER2 positive defined either HER2 IHC3+ or HER2 IHC 2+/ISH+.

Key Exclusion Criteria:

  • History of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.

  • Any clinically apparent ≥ Grade 2 pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months of the trial enrollment, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's, sarcoidosis), or prior pneumonectomy.

  • Current evidence of ≥ Grade 2 keratitis or other corneal abnormality.

  • Evidence of a clinically significant (≥ Grade 2) abnormality on slit-lamp examination or other clinically significant ophthalmologic finding, as determined by an ophthalmologist.

  • Evidence of clinically significant (≥ Grade 2) confluent superficial keratitis, a corneal epithelial defect, a corneal ulcer, or stromal opacity.

  • Participant must not use contact lenses while participating in this study.

  • Central nervous system metastatic disease unless treated with definitive local therapy (surgical resection, stereotactic radiotherapy, or whole brain radiotherapy) and participant is clinically, radiologically and neurologically stable for at least 4 weeks prior to the first dose of study drug not on steroid therapy or are on a stable or decreasing dose of steroids for at least 7 days prior to first dose of study drug. Prophylactic anticonvulsant medications are allowed.

  • Active second malignancy or history of another malignancy within the last 2 years with the exception of:

    • Treated, non-melanoma skin cancers
    • Treated carcinoma in situ (CIS) (e.g., breast, cervix)
    • Controlled, superficial carcinoma of the urinary bladder
    • T1a or b carcinoma of the prostate treated according to local standard of care, with prostate specific antigen (PSA) within normal limits (WNL) for the institution
    • Papillary thyroid carcinoma Stage I treated surgically for cure
  • Clinically significant cardiovascular disease or condition

  • Clinically significant liver disease

  • Any other serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever > 38ºC within 2 weeks prior to first trial drug administration.

  • Any other serious, life-threatening, or unstable preexisting medical condition (aside from the underlying malignancy), including significant organ system dysfunction, or clinically significant laboratory abnormality(ies), which, in the opinion of the Investigator, would either compromise the participant's safety or interfere with obtaining informed consent, compliance with trial procedures, or evaluation of the safety of the trial drug.

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: Dose Escalation Cohort (Part 1)

Each patient will receive repeat doses (by intravenous (IV) infusions) on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.

IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent.

Eksperimentel: Dose Expansion: HER2+ Breast Cancer Participants

Each patient will receive IKS014 at the recommended dose defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.

IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent.

Eksperimentel: Dose Expansion: HER2 Low Breast Cancer Participants

Each patient will receive IKS014 at the recommended dose defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.

IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent.

Eksperimentel: Dose Expansion: HER2+ Gastric Cancer or Gastro-esophageal Junction Participants

Each patient will receive IKS014 at the recommended dose defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.

IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent.

Eksperimentel: Dose Expansion: HER2 Low Gastric Cancer or Gastro-esophageal Junction Participants

Each patient will receive IKS014 at the recommended dose defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.

IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent.

Eksperimentel: Dose Expansion: HER2 Solid Tumor Cancer Participants

Each patient will receive IKS014 at the recommended dose defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.

IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Recommended Phase 2 Dose (Part 1)
Tidsramme: Up to 24 months

Based on tolerability, preliminary anti-tumor activity, and pharmacokinetics

Up to 24 months
Objective Response Rate (Part 2)
Tidsramme: Up to 24 months

Anti-tumor activity will be assessed by RECIST 1.1

Up to 24 months

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Objective Response Rate (Part 1)
Tidsramme: Up to 24 months

Anti-tumor activity will be assessed by RECIST 1.1

Up to 24 months
Plasma Concentrations of IKS014 (Part 1 and 2)
Tidsramme: Up to 48 months

Pharmacokinetic parameters will be determined from observed concentrations of IKS014

Up to 48 months
Evaluation of the immunogenicity of IKS014 (Part 1 and 2)
Tidsramme: Up to 48 months

Occurrence of ADA measured in serum at selected timepoints during the study

Up to 48 months

Samarbejdspartnere og efterforskere

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

Sponsor

Efterforskere

  • Studieleder: James O'Leary, MD, Iksuda Therapeutics

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)

14. september 2023

Primær færdiggørelse (Anslået)

1. december 2026

Studieafslutning (Anslået)

1. december 2027

Datoer for studieregistrering

Først indsendt

14. maj 2023

Først indsendt, der opfyldte QC-kriterier

14. maj 2023

Først opslået (Faktiske)

24. maj 2023

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

28. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

23. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Andre undersøgelses-id-numre

  • IKS014-01

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

produkt fremstillet i og eksporteret fra U.S.A.

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .