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PRE-I-SPY Phase I/Ib-Programm (PRE-ISPY)

25. September 2026 aktualisiert von: QuantumLeap Healthcare Collaborative

VOR-Untersuchung serieller Studien zur Vorhersage Ihrer therapeutischen Reaktion mithilfe von Bildgebung und molekularer Analyse: Eine Phase-I/Ib-Plattformstudie

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.

Studienübersicht

Status

Rekrutierung

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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.

Studientyp

Interventionell

Einschreibung (Geschätzt)

280

Phase

  • Phase 2
  • Phase 1

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studieren Sie die Kontaktsicherung

Studienorte

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

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Nicht randomisiert
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
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.
Arzneimittel: 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;

Andere Namen:
  • Evorpacept
Arzneimittel: Fam-Trastuzumab Deruxtecan-Nxki

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

Andere Namen:
  • 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.
Arzneimittel: Zanidatamab

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

Andere Namen:
  • ZW25
  • zani
  • Ziihera
Arzneimittel: Tucatinib

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

Andere Namen:
  • 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.
Arzneimittel: TTX-MC138

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

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Incidence of Adverse Events related to the treatment
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Progression Free Survival (PFS) - descriptive
Zeitfenster: 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
Zeitfenster: 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

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

QuantumLeap Healthcare Collaborative

Mitarbeiter

Pfizer
Jazz Pharmaceuticals
ALX Oncology Inc.
TransCode Therapeutics

Ermittler

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

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

15. Februar 2023

Primärer Abschluss (Geschätzt)

30. Dezember 2030

Studienabschluss (Geschätzt)

30. Dezember 2031

Studienanmeldedaten

Zuerst eingereicht

22. April 2022

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

10. Mai 2023

Zuerst gepostet (Tatsächlich)

22. Mai 2023

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

30. September 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

25. September 2026

Zuletzt verifiziert

1. September 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • I-SPY-P1

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Ja

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

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