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Programa PRE-I-SPY Fase I/Ib (PRE-ISPY)

25 de setembro de 2026 atualizado por: QuantumLeap Healthcare Collaborative

Pré-investigação de estudos em série para prever sua resposta terapêutica com imagens e análise molecular: um teste de plataforma de fase I/Ib

PRE-ISPY Phase I/II (I-SPY-P1) is an open-label, multisite platform study with multiple ongoing drug regimen arms added by protocol amendment which is designed to evaluate single agents or combinations in locally advanced, incurable, or metastatic solid tumors and/or oligometastatic malignancy and/or a high risk of recurrence following prior treatment with curative intent. The overall goal is moving promising drug regimens into a larger phase II (or III) trial and in general could feed the neoadjuvant breast I-SPY 2 Trial (NCT01042379) and/or other oncology solid tumor trial in a timely manner.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

The PRE-ISPY/I-SPY-P1 study is a platform trial with multiple ongoing drug regimen arms. Each drug regimen arm may have a Phase I dose-finding group (Part 1), a dose-expansion group (Part 2), and/or a Phase II component. Participant eligibility may vary according to the investigational arm or the part within the study arm, including with respect to diagnosis. Arms may restrict enrollment to a certain molecular pathway abnormality or histologic diagnosis (e.g. metastatic TNBC or MRD CRC). The trial allows for various study arm designs, with the goal to complete analysis of a study arm in 12 to 18 months.

Tipo de estudo

Intervencional

Inscrição (Estimado)

280

Estágio

  • Fase 2
  • 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

Estude backup de contato

Locais de estudo

  • Estados Unidos
    • Alabama
      • Birmingham, Alabama, Estados Unidos, 35233
        • Recrutamento
        • The University of Alabama at Birmingham O'Neal Comprehensive Cancer Center
        • Investigador principal:
          • Erica Stringer-Reasor, MD
        • Contato:
        • Contato:
        • Subinvestigador:
          • Nusrat Jahan, MD
        • Subinvestigador:
          • Gabrielle Rocque, MD
        • Subinvestigador:
          • Midhun Malla, MD
    • Arizona
      • Phoenix, Arizona, Estados Unidos, 85054
        • Ainda não está recrutando
        • Mayo Clinic Comprehensive Cancer Center
        • Subinvestigador:
          • Mojun Zhu, MD
        • Contato:
        • Subinvestigador:
          • Lida Mina, MD
    • Colorado
      • Aurora, Colorado, Estados Unidos, 80045
        • Ativo, não recrutando
        • University of Colorado Cancer Center
    • Florida
      • Tampa, Florida, Estados Unidos, 33612
        • Ativo, não recrutando
        • Moffitt Cancer Center
    • Illinois
      • Chicago, Illinois, Estados Unidos, 60637
        • Recrutamento
        • The University of Chicago Medicine Comprehensive Cancer Center
        • Investigador principal:
          • Nan Chen, MD
        • Subinvestigador:
          • Rita Nanda, MD
        • Contato:
        • Subinvestigador:
          • Ardaman Shergill, MD, MSPH
      • New Lenox, Illinois, Estados Unidos, 60451
        • Recrutamento
        • UChicago Medicine Comprehensive Cancer Center at Silver Cross Hospital
        • Investigador principal:
          • Nan Chen, MD
        • Contato:
      • Orland Park, Illinois, Estados Unidos, 60462
        • Recrutamento
        • UChicago Medicine Orland Park
        • Investigador principal:
          • Nan Chen, MD
        • Contato:
    • Minnesota
      • Minneapolis, Minnesota, Estados Unidos, 55455
        • Recrutamento
        • University of Minnesota Masonic Cancer Center
        • Investigador principal:
          • David Potter, MD, PhD
        • Contato:
        • Contato:
        • Subinvestigador:
          • Anne Blaes, MD, MS
        • Subinvestigador:
          • Emil Lou, MD, PhD
      • Rochester, Minnesota, Estados Unidos, 55905
        • Ainda não está recrutando
        • Mayo Clinic Comprehensive Cancer Center
        • Subinvestigador:
          • Zhaohui Jin, MD
        • Contato:
        • Investigador principal:
          • Roberto A Leon-Ferre, MD
    • Texas
      • Houston, Texas, Estados Unidos, 77030
        • Ativo, não recrutando
        • The University of Texas MD Anderson Cancer Center

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

General Inclusion Criteria (GIC):

  • GIC1: The participant must have ability to understand and willingness to provide signed written informed consent prior to any study related assessments and procedures and for collection of archival FFPE blocks for research. If FFPE blocks cannot be submitted, 20 to 40 freshly cut FFPE tissue slices (4 to 7 microns thick each) from a representative FFPE block, mounted on charged glass slides and left unstained will be acceptable. This criteria can be modified in specific drug regimens.

  • GIC2: Age ≥ 18 years at the time of signing the informed consent

  • GIC3: Gender: Male or female (premenopausal and postmenopausal)

  • GIC4: ECOG performance status Grade 0-2. This criteria can be modified in specific drug regimens.

  • GIC5: Estimated life expectancy > 12 weeks at the start of investigational medicinal product (IMP) treatment.

  • GIC6: Adequate organ function, evidenced by the following laboratory results within 30 days of the start of IMP:

    • Absolute neutrophil count ≥ 1,500/mm3
    • Platelet count ≥ 100,000/mm3
    • Hemoglobin ≥ 9.0 g/dL with no blood transfusion in the past 28 days
    • Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
    • Estimated Creatinine clearance (using Cockcroft-Gault formula) ≥ 60 mL/min for small molecules and >30 mL/min for monoclonal antibodies unless otherwise specified in the Arm Specific Eligibility.

These cut-off values may be modified with supporting data for specific drug regimens.

  • GIC7: Non-Pregnant: Serum or urine pregnancy test must be negative within 14 days of IMP treatment start in women of childbearing potential. Pregnancy testing does not need to be pursued in patients who are judged as postmenopausal before enrollment, or who have undergone bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation. If male, they must agree to refrain from donating sperm during treatment.
  • GIC8: Contraception: Women of childbearing potential and men must be willing to use adequate contraception for the duration of protocol treatment. Additional information regarding contraception for the specific treatment arm will be added to the drug arm description. Adequate contraception is defined as one highly effective form (i.e., abstinence, (fe)male sterilization) OR two effective forms (e.g., non-hormonal IUD and condom / occlusive cap with spermicidal foam / gel / film / cream / suppository).
  • GIC9: Prior therapy effects: Resolution of all acute toxic effects of prior therapy, including radiotherapy, to grade ≤1 and neuropathy to grade ≤2 (except toxicities not considered a safety risk for the patient) and recovery from surgical procedures.
  • GIC10: Participant compliance: Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  • Additional arm specific inclusion criteria as needed by drug arm regimen

General Exclusion Criteria (GEC):

  • GEC1: Wash out periods: Other anticancer therapy within the following period:

    • chemotherapy or investigational agents, 3 weeks
    • mitomycin C and nitrosoureas, 6 weeks
    • if radiotherapy is less than 5 days, 1 week wash out; if >5 days, then 2 weeks washout
    • for radionuclides, contact Study PI or Study Chaperone to determine washout
    • targeted therapy, 2 weeks
    • MAbs, ADCs, and immunotherapy, 3 weeks
    • endocrine therapy, no washout needed

  • GEC2: Concurrent therapy with other Investigational Products.

  • GEC3: Prior history of drug/regimen hypersensitivity: History of infusion-related reactions and/or hypersensitivity to IMP or excipients of the study drug/drugs which led to permanent discontinuation of the treatment.

  • GEC4: Uncontrolled intercurrent illness including active infection, diabetes, adrenal insufficiency, pulmonary embolism, stroke in the past 6 months, or psychiatric illness/social situations that would limit compliance with study requirements.

  • GEC5: Cardiovascular disease: History (within 6 months prior to start IMP) of clinically significant cardiovascular disease such as unstable angina, congestive heart failure (CHF), myocardial infarction, uncontrolled hypertension, cardiac arrhythmia requiring medication, or baseline corrected QT by Fridericia's formula (QTcF) length > 470 msec for men and women. The QTcF cut-off value may be modified with supporting data for specific drug regimens.

  • GEC6: CNS tumoral spread: Active uncontrolled/symptomatic central nervous system cancer/spinal cord compression. Previously treated and clinically stable lesions, as per Investigator's judgment, are permitted. Exception: Newly discovered asymptomatic lesions that are not life threatening and do not require urgent local treatment to ensure patient safety, including new parenchymal lesions or leptomeningeal disease, if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy, after consultation with study regimen chaperones, may be permitted. This criteria can be modified in specific drug regimens.

  • GEC7: Liver disease: Patients with clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis.

  • GEC8: Recent major surgery within 4 weeks prior to start IMP treatment

  • GEC9: Pregnancy or breastfeeding

  • GEC10: Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.

  • GEC11: Other conditions, which in the opinion of the investigator, would compromise the safety of the patient or the patient's ability to complete the study.

  • GEC12: Concomitant malignancies: A diagnosis of a malignancy in the 2 years prior to starting study treatment other than the disease under study. Exceptions include indolent or definitively treated malignancy not expected to require treatment during the study, affect the safety of participants, or affect the endpoints of the trial.

  • Additional arm specific exclusion criteria as needed by drug arm regimen

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 Paralela
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: PRE1 ALX148 (Evorpacept) + Fam-Trastuzumab Deruxtecan-Nxki (T-DXd, Enhertu®)

The combination of T-DXd and ALX148 aims to explore the anti-tumoral effects of trastuzumab, of the topoisomerase inhibitor DXd and of the CD47-blocking agent ALX148. The rationale for this combination is that ALX148 is hypothesized, based on preclinical data, to facilitate antibody-dependent cellular phagocytosis (ADCP) of HER2 expressing (>HER2 1+) breast cancer binding T-DXd while cancer cell intrinsic or bystander cytotoxicity of T-DXd will result in the release of neoantigens promoting immune mediated antitumor activity in the tumor microenvironment.
Medicamento: ALX148

Starting dose Dose Level 1 30mg/kg IV Q3W; Dose Level Minus 1 20 mg/kg IV Q3W (if needed); Dose Level 2 45 mg/kg IV Q3W;

Outros nomes:
  • Evorpacept
Medicamento: Fam-Trastuzumab Deruxtecan-Nxki

5.4 mg/kg IV Q3W; allowed to dose reduce after DLT observation period

Outros nomes:
  • Enhertu
  • T-DXd
Experimental: PRE2 Zanidatamab (Ziihera®, ZW25, zani) + Tucatinib (TUKYSA®)

Zanidatamab is a bispecific IgG1-like antibody directed against two distinct HER2 epitopes. It induces formation of receptor clusters and internalization resulting in downregulation. It also inhibits growth factor-dependent and -independent tumor cell proliferation and potently activates ADCC, ADCP, and CDC. FDA approved for metastatic HER2+ bile duct cancer.

Tucatinib is a highly selective, small molecule tyrosine kinase inhibitor (TKI) of HER2 compared to other TKI's (i.e., EGFR). It is well tolerated, crosses the blood brain barrier and can treat CNS disease. FDA approved for HER2+ breast cancer.

Given the promising clinical data for each of these drugs which have different mechanisms, the effect of zanidatamab after T-DXd (Enhertu®) in breast cancer patients, and the favorable toxicity profile of both drugs, we hypothesize that the combination of tucatinib and zanidatamab will be well tolerated and more efficacious than either drug alone for the treatment of HER2+ breast cancer.
Medicamento: Zanidatamab

20 mg/kg IV Q2W on Day 1 and Day 15 of each 28 day cycle

Outros nomes:
  • ZW25
  • zani
  • Ziihera
Medicamento: Tucatinib

Dose Level 1: 300 mg PO BID daily; Dose Leve Minus 1: 250 mg PO BID daily

Outros nomes:
  • TUKYSA
Experimental: PRE4 TTX-MC138

TTX-MC138 is an antisense oligonucleotide targeting miR-10b. MicroRNA-10b (miR-10b) was identified in metastatic cell lines and tumors from participants with metastatic breast cancer and has been shown to regulate the ability of metastatic tumor cells to survive outside of the primary tumor and to migrate and invade surrounding tissue. miRNA-10b is critical to tumor growth and is a master regulator of metastatic cell viability in a range of cancers, including breast, pancreatic, ovarian, colon cancer, glioblast.

This is a PRE-ISPY PHASE II study of TTX-MC138 as interception treatment in patients with Stage I-III adenocarcinoma of the colon or rectum (Cohort A) who have documented minimal residual disease by tumor informed ctDNA, that was collected following completion of standard therapy with curative intent.
Medicamento: TTX-MC138

4.8 mg/kg Q4W IV on Day 1 for up to 12 cycles as interception therapy

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Incidence of Adverse Events related to the treatment
Prazo: Start of treatment to 30 days post treatment (estimated 12 -18 months)

Evaluate the number of adverse events related to the treatment according to the current version of CTCAE during the trial.
Start of treatment to 30 days post treatment (estimated 12 -18 months)
For Phase Ib Part 1 study design: Incidence of Dose Limiting Toxicities (DLTs) at each dose level
Prazo: DLT observation period: Start of treatment to end of Cycle 1

To determine the safety and tolerability of new agents/regimens in participants with certain advanced solid tumors and breast cancer. DLT rate (number of participants who experience a protocol defined DLT/total number of DLT cohort participants at that dose).
DLT observation period: Start of treatment to end of Cycle 1
For select drug arms, Maximum Tolerated Dose (MTD)
Prazo: Start of treatment to the date of last participant at end of DLT observation period at highest dose level (estimated 6 months)

The maximum dose level (mg/kg) which is not eliminated.
Start of treatment to the date of last participant at end of DLT observation period at highest dose level (estimated 6 months)
For Phase Ib Part 1 drug arms, Recommended Phase 2 Dose (RP2D)
Prazo: Start of treatment to the date of last participant at highest dose level (estimated 6 months)

Using all available data, computation of RP2D (mg/kg), which may not be the MTD.
Start of treatment to the date of last participant at highest dose level (estimated 6 months)
Overall Response Rate (ORR)
Prazo: Start of treatment to 12 months

To obtain preliminary efficacy data of the new agents/regimens in participants with certain advanced solid tumors and breast cancer.
Start of treatment to 12 months
Duration of Response (DOR)
Prazo: Start of treatment to 12 months

To obtain preliminary efficacy data of the new agents/regimens in participants with certain advanced solid tumors and breast cancer.
Start of treatment to 12 months

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Progression Free Survival (PFS) - descriptive
Prazo: Start of treatment to 12 months

To provide descriptive assessment of Progression Free Survival (PFS) of the new agents/regimens with certain advanced solid tumors and breast cancer
Start of treatment to 12 months
Clinical Benefit Rate (CBR) at 6 months
Prazo: Start of treatment to 6 months

To obtain preliminary Clinical Benefit Rate (CBR) at 6 months of participants treated with the new agents/regimens.
Start of treatment to 6 months

Colaboradores e Investigadores

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

Patrocinador

QuantumLeap Healthcare Collaborative

Colaboradores

Pfizer
Jazz Pharmaceuticals
ALX Oncology Inc.
TransCode Therapeutics

Investigadores

  • Investigador principal: Paula R Pohlmann, MD, MSc, PhD, M.D. Anderson Cancer Center

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)

15 de fevereiro de 2023

Conclusão Primária (Estimado)

30 de dezembro de 2030

Conclusão do estudo (Estimado)

30 de dezembro de 2031

Datas de inscrição no estudo

Enviado pela primeira vez

22 de abril de 2022

Enviado pela primeira vez que atendeu aos critérios de CQ

10 de maio de 2023

Primeira postagem (Real)

22 de maio de 2023

Atualizações de registro de estudo

Última Atualização Postada (Real)

30 de setembro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

25 de setembro de 2026

Última verificação

1 de setembro de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • I-SPY-P1

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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