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IKS03 em pacientes com linfomas não Hodgkin avançados de células B

2 de novembro de 2026 atualizado por: Iksuda Therapeutics Ltd.

Um estudo de escalonamento e expansão de dose de coorte de Fase 1 para determinar a segurança, a tolerância, a dose máxima tolerada e a atividade antineoplásica preliminar de IKS03 em pacientes com linfomas não Hodgkin (NHL) avançados de células B

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).

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

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.

Tipo de estudo

Intervencional

Inscrição (Estimado)

140

Estágio

  • Fase 1

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Locais de estudo

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

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Não randomizado
  • Modelo Intervencional: Atribuição sequencial
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: 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.
Medicamento: IKS03

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

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

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

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

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

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Recommended Phase 2 Dose (Part I)
Prazo: 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)
Prazo: up to 42 months

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

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Evaluation of the immunogenicity of IKS03 (Part I and II)
Prazo: 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)
Prazo: 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)
Prazo: Up to 42 months

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

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Iksuda Therapeutics Ltd.

Investigadores

  • Diretor de estudo: Debra Wood, MD, Iksuda Therapeutics

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

5 de setembro de 2023

Conclusão Primária (Estimado)

1 de setembro de 2027

Conclusão do estudo (Estimado)

1 de setembro de 2028

Datas de inscrição no estudo

Enviado pela primeira vez

2 de maio de 2022

Enviado pela primeira vez que atendeu aos critérios de CQ

6 de maio de 2022

Primeira postagem (Real)

9 de maio de 2022

Atualizações de registro de estudo

Última Atualização Postada (Real)

3 de novembro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

2 de novembro de 2026

Última verificação

1 de novembro de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • IKS03-01

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Sim

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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