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PRE-I-SPY Phase I/Ib 프로그램 (PRE-ISPY)

2026년 9월 25일 업데이트: QuantumLeap Healthcare Collaborative

영상 및 분자 분석으로 치료 반응을 예측하기 위한 연속 연구의 사전 조사: I/Ib상 플랫폼 시험

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.

연구 개요

상태

모병

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록 (추정된)

280

단계

  • 2 단계
  • 1단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 연락처 백업

연구 장소

  • 미국
    • Alabama
      • Birmingham, Alabama, 미국, 35233
        • 모병
        • The University of Alabama at Birmingham O'Neal Comprehensive Cancer Center
        • 수석 연구원:
          • Erica Stringer-Reasor, MD
        • 연락하다:
        • 연락하다:
        • 부수사관:
          • Nusrat Jahan, MD
        • 부수사관:
          • Gabrielle Rocque, MD
        • 부수사관:
          • Midhun Malla, MD
    • Arizona
      • Phoenix, Arizona, 미국, 85054
        • 아직 모집하지 않음
        • Mayo Clinic Comprehensive Cancer Center
        • 부수사관:
          • Mojun Zhu, MD
        • 연락하다:
        • 부수사관:
          • Lida Mina, MD
    • Colorado
      • Aurora, Colorado, 미국, 80045
        • 모집하지 않고 적극적으로
        • University of Colorado Cancer Center
    • Florida
      • Tampa, Florida, 미국, 33612
        • 모집하지 않고 적극적으로
        • Moffitt Cancer Center
    • Illinois
      • Chicago, Illinois, 미국, 60637
        • 모병
        • The University of Chicago Medicine Comprehensive Cancer Center
        • 수석 연구원:
          • Nan Chen, MD
        • 부수사관:
          • Rita Nanda, MD
        • 연락하다:
        • 부수사관:
          • Ardaman Shergill, MD, MSPH
      • New Lenox, Illinois, 미국, 60451
        • 모병
        • UChicago Medicine Comprehensive Cancer Center at Silver Cross Hospital
        • 수석 연구원:
          • Nan Chen, MD
        • 연락하다:
      • Orland Park, Illinois, 미국, 60462
        • 모병
        • UChicago Medicine Orland Park
        • 수석 연구원:
          • Nan Chen, MD
        • 연락하다:
    • Minnesota
      • Minneapolis, Minnesota, 미국, 55455
        • 모병
        • University of Minnesota Masonic Cancer Center
        • 수석 연구원:
          • David Potter, MD, PhD
        • 연락하다:
        • 연락하다:
        • 부수사관:
          • Anne Blaes, MD, MS
        • 부수사관:
          • Emil Lou, MD, PhD
      • Rochester, Minnesota, 미국, 55905
        • 아직 모집하지 않음
        • Mayo Clinic Comprehensive Cancer Center
        • 부수사관:
          • Zhaohui Jin, MD
        • 연락하다:
        • 수석 연구원:
          • Roberto A Leon-Ferre, MD
    • Texas
      • Houston, Texas, 미국, 77030
        • 모집하지 않고 적극적으로
        • The University of Texas MD Anderson Cancer Center

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 이상 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위화되지 않음
  • 중재 모델: 병렬 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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.
의약품: 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;

다른 이름들:
  • 이보퍼셉트
의약품: Fam-Trastuzumab Deruxtecan-Nxki

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

다른 이름들:
  • 엔헤르투
  • T-DXd
실험적: 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.
의약품: Zanidatamab

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

다른 이름들:
  • ZW25
  • 자니
  • Ziihera
의약품: Tucatinib

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

다른 이름들:
  • 투키사
실험적: 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.
의약품: TTX-MC138

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

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Incidence of Adverse Events related to the treatment
기간: 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
기간: 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)
기간: 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)
기간: 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)
기간: 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)
기간: 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

2차 결과 측정

결과 측정
측정값 설명
기간
Progression Free Survival (PFS) - descriptive
기간: 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
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

QuantumLeap Healthcare Collaborative

협력자

Pfizer
Jazz Pharmaceuticals
ALX Oncology Inc.
TransCode Therapeutics

수사관

  • 수석 연구원: Paula R Pohlmann, MD, MSc, PhD, M.D. Anderson Cancer Center

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2023년 2월 15일

기본 완료 (추정된)

2030년 12월 30일

연구 완료 (추정된)

2031년 12월 30일

연구 등록 날짜

최초 제출

2022년 4월 22일

QC 기준을 충족하는 최초 제출

2023년 5월 10일

처음 게시됨 (실제)

2023년 5월 22일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 9월 30일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 9월 25일

마지막으로 확인됨

2026년 9월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • I-SPY-P1

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다