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IKS03 hos patienter med avancerede B-celle non-Hodgkin-lymfomer

2. november 2026 opdateret af: Iksuda Therapeutics Ltd.

Et fase 1 kohorte-dosisoptrapnings- og udvidelsesforsøg for at bestemme sikkerheden, tolerancen, den maksimale tolererede dosis og den foreløbige antineoplastiske aktivitet af IKS03 hos patienter med avancerede B-celle non-Hodgkin-lymfomer (NHL)

This first-in-human study will evaluate the recommended dose for further clinical development, safety, tolerability, antineoplastic activity, immunogenicity, pharmacokinetics and pharmacodynamics of IKS03, a CD19 targeting antibody-drug conjugate, in patients with advanced B cell non-Hodgkin lymphoma (NHL).

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

The study will consist of 2 parts: dose-escalation (Part I) and dose-expansion (Part II). The dose-escalation part (Part I) of the study is to evaluate the safety and tolerability of increasing dose levels of IKS03 to establish a recommended Phase 2 dose (RP2D); and the dose-expansion part (Part II) of the study is to further evaluate the safety, pharmacokinetics/pharmacodynamics, and efficacy of IKS03 at the RP2D.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

140

Fase

  • Fase 1

Kontakter og lokationer

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

Studiekontakt

Studiesteder

  • Australien
    • New South Wales
      • Westmead, New South Wales, Australien, 2145
        • Rekruttering
        • Westmead Hospital
        • Ledende efterforsker:
          • Amanda Johnston, MD
    • South Australia
      • Adelaide, South Australia, Australien
        • Rekruttering
        • Royal Adelaide Hospital
        • Kontakt:
          • Pratyush Giri, MBBS
        • Ledende efterforsker:
          • Pratyush Giri, MBBS
    • Tasmania
      • Hobart, Tasmania, Australien, 7000
        • Rekruttering
        • Royal Hobart Hospital
        • Ledende efterforsker:
          • Rosemary Harrup, MD
    • Western Australia
      • Perth, Western Australia, Australien
        • Rekruttering
        • Linear Clinical Research
        • Kontakt:
          • Katharine Lewis, MD
        • Ledende efterforsker:
          • Katharine Lewis, MD
  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Rekruttering
        • Jewish General Hospital
        • Ledende efterforsker:
          • Sarit Assouline, MD
        • Kontakt:
          • Sarit Assouline, MD
  • Forenede Stater
    • Maryland
      • Baltimore, Maryland, Forenede Stater, 21201
        • Trukket tilbage
        • University of Maryland Baltimore
  • Italien
      • Candiolo, Italien
        • Rekruttering
        • Istituto Nazionale Oncologico Candiolo
        • Kontakt:
          • Umberto Vitolo, M.D.
        • Ledende efterforsker:
          • Umberto Vitolo, M.D.
      • Milan, Italien
        • Rekruttering
        • Istituto Europeo di Oncologia
        • Kontakt:
          • Enrico Derenzini, M.D.
        • Ledende efterforsker:
          • Enrico Derenzini, M.D.
      • Milan, Italien
        • Rekruttering
        • Istituto Europeo Clinico Humanitas
        • Kontakt:
          • Carmelo Carlo-Stella, M.D.
        • Ledende efterforsker:
          • Carmelo Carlo-Stella, M.D.
      • Milan, Italien
        • Rekruttering
        • Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele
        • Kontakt:
          • Andres Jose Maria Ferreri, M.D.
        • Ledende efterforsker:
          • Andres Jose Maria Ferreri, M.D.
  • Spanien
      • Badalona, Spanien
        • Rekruttering
        • Institut Catala D'Oncologia
        • Kontakt:
          • Mireia Franch-Sarto, M.D.
        • Ledende efterforsker:
          • Mireia Franch-Sarto, M.D.
      • Madrid, Spanien
        • Rekruttering
        • Hospital Universitario Quironsalud Madrid
        • Kontakt:
          • Maria del Carmen Martinez-Chamorro, M.D.
        • Ledende efterforsker:
          • Maria del Carmen Martinez-Chamorro, M.D.
      • Salamanca, Spanien
        • Rekruttering
        • Hospital Clinico Universitario de Salamanca
        • Kontakt:
          • Alejandro Martin Garcia-Sancho, M.D.
        • Ledende efterforsker:
          • Alejandro Martin Garcia-Sancho, M.D.

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:

  1. Males or females, ≥ 18 years of age

  2. Part I: documented B cell NHL (any subtype except Burkitt lymphoma, Waldenström macroglobulinemia, chronic lymphocytic leukemia); previously confirmed CD19-positive if feasible

  3. Part II: documented B cell NHL (subtypes to be determined); confirmed CD19-positive; possible expansion cohorts may include:

    1. Diffuse large B cell lymphoma (including germinal center B cell type, activated B cell type)
    2. Follicular lymphoma (including duodenal-type follicular lymphoma)
    3. Mantle cell lymphoma
    4. B cell lymphomas not specified

  4. If B cell NHL subtype likely to have bone marrow involvement must be willing to undergo bone marrow biopsy in the event of an on-study complete response to confirm response

  5. NHL that is relapsed, refractory to, or intolerant of existing therapy(ies) with known curative potential, or for which no standard therapy is available; must have received at least 2 prior lines of systemic therapy

  6. Must be in need of systemic treatment and not require immediate cytoreductive therapy

  7. Part I: measurable or non-measurable disease

  8. Part II: measurable disease according to The Revised Criteria/Lugano Classification

  9. Part I: screening tumor biopsy requested, but optional; Part 2: patient must agree to screening tumor biopsy

  10. ECOG performance status 0 or 1

  11. Women of childbearing potential and fertile men agreeing to use two effective methods of contraception (including a highly effective method of contraception); women beginning 2 weeks prior to the first dose, men beginning prior to the first dose, and both continuing until 8 months after the last dose of study drug; male patients must also agree to refrain from sperm donation during this period.

  12. Ability to understand and give written informed consent

Exclusion Criteria:

  1. Women who are pregnant or intending to become pregnant before, during, or within 8 months after the last dose of study drug; women who are breastfeeding

  2. Patients documented to be CD19-negative

  3. Central nervous system (CNS) lymphoma, leptomeningeal infiltration, or spinal cord compression not controlled by prior surgery or radiotherapy; symptoms suggesting CNS involvement

  4. Part 2: History of another malignancy within 2 years, with the exception of:

    1. Treated, non-melanoma skin cancers
    2. Treated carcinoma in situ (e.g., breast, cervix)
    3. Controlled, superficial carcinoma of the urinary bladder
    4. T1a or b prostate carcinoma treated according to standard of care, with PSA within normal limits
    5. Papillary thyroid carcinoma Stage I treated surgically for cure

  5. Any of the following hematologic abnormalities at baseline (transfusion allowed > 5 days previous):

    1. Hemoglobin < 8.0 g/dL
    2. Absolute neutrophil count < 1,000 per mm3
    3. Platelet count < 75,000 per mm3

  6. Any of the following laboratory abnormalities at baseline:

    1. Total bilirubin > 1.5 × upper limit of normal (ULN); > 3 × ULN if with Gilbert's Syndrome
    2. AST or ALT > 3 × ULN; > 5 × ULN if due to hepatic involvement by tumor
    3. Estimated GFR ≤ 60 mL/min corrected for BSA
    4. Albuminuria defined as urine albumin to creatinine ratio < 30 mg/g or < 3 mg/mmol) by spot urine albumin

  7. Any of the following coagulation parameter abnormalities at baseline unless on a stable dose of anticoagulant therapy for a prior thrombotic event:

    1. PT or INR > 1.5 × ULN; > 3× ULN if anticoagulated)
    2. PTT > 1.5 × ULN; > 3× ULN if anticoagulated

  8. Any of the following laboratory abnormalities at baseline aimed at assessing renal function:

    1. Estimated glomerular filtration rate (eGFR) ≤ 60 mL/min, corrected for BSA.
    2. Albuminuria defined as urine albumin to creatinine ratio (UACR) ≥ 45 mg/g or ≥ 4.5 mg/mmol by spot urine albumin

  9. Patients with:

    1. Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks unless adequately treated and stable
    2. Active uncontrolled bleeding or a known bleeding diathesis

  10. Significant cardiovascular disease or condition, including:

    1. Congestive heart failure or angina pectoris requiring therapy
    2. Ventricular arrhythmia requiring therapy or other uncontrolled arrhythmia
    3. Severe conduction disturbance (e.g., 3rd degree heart block)
    4. QTc interval ≥ 480 milliseconds
    5. Left ventricular ejection fraction below the lower limit of normal or < 50% by MUGA scan or echocardiogram
    6. Class III or IV cardiovascular disease according to the New York Heart Association Functional Classification
    7. History of acute coronary syndromes (e.g., MI, unstable angina), coronary angioplasty, stenting, or bypass within 6 months

  11. Significant liver disease, including:

    1. Non-infectious hepatitis
    2. Hepatic cirrhosis (Child-Pugh Class B and Class C)

  12. Significant pulmonary disease or condition, including:

    1. Significant symptomatic COPD, as assessed by the Investigator
    2. History or any current evidence on imaging studies of interstitial lung disease, pulmonary fibrosis
    3. History of pulmonary inflammatory disease, pneumonitis, ARDS
    4. History of pneumonia within 1 month

  13. Significant corneal disease or condition, including history of or current evidence of keratitis

  14. Clinically significant CNS disease or condition including PML, epilepsy, vasculitis, or neurodegenerative disease. Also including TIA or stroke within 6 months

  15. Known HIV infection or AIDS

  16. Active hepatitis B virus or hepatitis C virus infection

  17. Any other serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever > 38ºC within 2 weeks

  18. Autoimmune disease or condition requiring systemic steroids or other immunosuppressive medications

  19. Unresolved Grade > 1 AE associated with any prior antineoplastic therapy (except persistent Grade 2 alopecia, peripheral neuropathy, decreased hemoglobin, neutropenia, lymphopenia, hypomagnesemia, and/or endocrine end-organ failure being adequately managed by HRT)

  20. Known or suspected hypersensitivity to any of the excipients of formulated study drug

  21. Inadequate recovery from a surgical procedure, or a major surgical procedure within 4 weeks

  22. Any other serious, life-threatening, or unstable preexisting medical condition, including significant organ system dysfunction, or clinically significant laboratory abnormality(ies)

  23. A psychiatric disorder or altered mental status that would preclude understanding of the informed consent process

Drugs and Other Treatments to be Excluded:

  1. Receipt of:

    1. Any CD19-targeted therapy within 4 weeks
    2. Any tumor vaccine within 6 weeks (must have progressed if previously received)

  2. Prior autologous/allogeneic CAR-T therapy if known to be CD19-negative after

  3. Any other antineoplastic agent for the primary malignancy without delayed toxicity within 3 weeks or 5 plasma half-lives, whichever is shortest (except nitrosoureas and mitomycin C within 6 weeks)

  4. Any other investigational treatments within 3 weeks

  5. Drugs known to impair renal function, including:

    1. NSAIDS within 3 days
    2. Aminoglycoside antibiotics, amphotericin B, etc. within 1 week
    3. Bisphosphonates within 1 month

  6. Prior solid organ transplant

  7. Allogeneic HSCT within 6 months, or:

    1. If receiving immunosuppression
    2. If with active evidence of GVHD

  8. Autologous hematopoietic stem cell transplantation (HSCT) within 3 months

  9. Radiotherapy:

    1. To target lesions within 4 weeks unless progression of the lesion has been documented
    2. To non-target lesions within 1 week

  10. Live/live-attenuated vaccines against infectious diseases within 4 weeks

  11. Immunosuppressive or systemic glucocorticoid therapy (> 10 mg prednisone daily or equivalent) within 2 weeks

  12. Prophylactic use of hematopoietic growth factors within 1 week

  13. Herbal therapies and supplements within 2 weeks

  14. Strong inhibitors of cytochrome P450 within 2 weeks

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 criterion is met.
Medicin: IKS03

IKS03 is a human monoclonal antibody (Ab) targeting CD19 linked to a pyrrolobenzodiazepine (PBD) pro-drug as the cytotoxic agent.
Eksperimentel: Dose Expansion: Diffuse-Large B-Cell Lymphoma Participants

Each patient will receive IKS03 at the RP2D defined in Part I on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
Medicin: IKS03

IKS03 is a human monoclonal antibody (Ab) targeting CD19 linked to a pyrrolobenzodiazepine (PBD) pro-drug as the cytotoxic agent.
Eksperimentel: Dose Expansion: Follicular Cell Lymphoma Participants

Each patient will receive IKS03 at the RP2D defined in Part I on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
Medicin: IKS03

IKS03 is a human monoclonal antibody (Ab) targeting CD19 linked to a pyrrolobenzodiazepine (PBD) pro-drug as the cytotoxic agent.
Eksperimentel: Dose Expansion: Mantle Cell Lymphoma Participants

Each patient will receive IKS03 at the RP2D defined in Part I on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
Medicin: IKS03

IKS03 is a human monoclonal antibody (Ab) targeting CD19 linked to a pyrrolobenzodiazepine (PBD) pro-drug as the cytotoxic agent.
Eksperimentel: Dose Expansion: Other B cell lymphoma (B-NHL not otherwise specified [NOS])

Each patient will receive IKS03 at the RP2D defined in Part I on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
Medicin: IKS03

IKS03 is a human monoclonal antibody (Ab) targeting CD19 linked to a pyrrolobenzodiazepine (PBD) pro-drug as the cytotoxic agent.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Recommended Phase 2 Dose (Part I)
Tidsramme: Up to 20 months

RP2D will be determined using dose limiting toxicities (DLTs) and all other available study data
Up to 20 months
Objective Response Rate (Part II)
Tidsramme: up to 42 months

Antineoplastic effects will be assessed by Criteria for Response Assessment: The Lugano Classification (Cheson 2014)
up to 42 months

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Evaluation of the immunogenicity of IKS03 (Part I and II)
Tidsramme: Up to 42 months

Occurrence of ADA measured in serum at selected timepoints during the study
Up to 42 months
Plasma Concentrations of IKS03 (Part I and II)
Tidsramme: Up to 42 months

Pharmacokinetic profile will be characterized by concentrations of IKS03
Up to 42 months
Determine recommended Phase 2 dose (RP2D) (Part II)
Tidsramme: Up to 42 months

Based on evidence of antitumor activity, acceptable tolerability, evidence of achieving target plasma concentration
Up to 42 months

Samarbejdspartnere og efterforskere

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

Sponsor

Iksuda Therapeutics Ltd.

Efterforskere

  • Studieleder: Debra Wood, 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)

5. september 2023

Primær færdiggørelse (Anslået)

1. september 2027

Studieafslutning (Anslået)

1. september 2028

Datoer for studieregistrering

Først indsendt

2. maj 2022

Først indsendt, der opfyldte QC-kriterier

6. maj 2022

Først opslået (Faktiske)

9. maj 2022

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

3. november 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

2. november 2026

Sidst verificeret

1. november 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • IKS03-01

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

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 .

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