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RECRUITING Phase 1 / Phase 2 ClinicalTrials.gov

PRE-ISPY Phase I/II Oncology Platform Program

Sponsor: QuantumLeap Healthcare Collaborative • ClinicalTrials.gov ID: NCT05868226

Registry updated: 2026-09-30
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Description

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.

Interventions

  • ALX148 (Drug)
    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;
  • Fam-Trastuzumab Deruxtecan-Nxki (Drug)
    5.4 mg/kg IV Q3W; allowed to dose reduce after DLT observation period
  • Zanidatamab (Drug)
    20 mg/kg IV Q2W on Day 1 and Day 15 of each 28 day cycle
  • Tucatinib (Drug)
    Dose Level 1: 300 mg PO BID daily; Dose Leve Minus 1: 250 mg PO BID daily
  • TTX-MC138 (Drug)
    4.8 mg/kg Q4W IV on Day 1 for up to 12 cycles as interception therapy

Eligibility criteria

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

Conditions

HER2-positive Breast Cancer Metastatic Cancer Metastatic Breast Cancer Metastatic HER2-positive Metastatic Breast Cancer HER2 Mutation-Related Tumors HER-2 Protein Overexpression HER2-negative Breast Cancer Triple Negative Breast Cancer HR Positive Hormone Receptor-positive Breast Cancer Estrogen Receptor Positive Tumor Progesterone Receptor-positive Breast Cancer Hormone Receptor Negative Breast Carcinoma Solid Tumor Solid Tumor, Adult Solid Carcinoma HER2 Low Breast Cancer HER2 Low Breast Carcinoma ER Positive Breast Cancer PR-positive Breast Cancer Minimal Residual Disease Colo-rectal Cancer Colon Cancer Rectal Cancer ctDNA Monitoring Colorectal Neoplasms Colonic Neoplasms Rectal Neoplasms Neoplasm, Residual Adenocarcinoma of Colon Adenocarcinoma

Locations

  • The University of Alabama at Birmingham O'Neal Comprehensive Cancer Center — Birmingham, Alabama, United States
  • Mayo Clinic Comprehensive Cancer Center — Phoenix, Arizona, United States
  • University of Colorado Cancer Center — Aurora, Colorado, United States
  • Moffitt Cancer Center — Tampa, Florida, United States
  • The University of Chicago Medicine Comprehensive Cancer Center — Chicago, Illinois, United States
  • UChicago Medicine Comprehensive Cancer Center at Silver Cross Hospital — New Lenox, Illinois, United States
  • UChicago Medicine Orland Park — Orland Park, Illinois, United States
  • University of Minnesota Masonic Cancer Center — Minneapolis, Minnesota, United States
  • Mayo Clinic Comprehensive Cancer Center — Rochester, Minnesota, United States
  • The University of Texas MD Anderson Cancer Center — Houston, Texas, United States
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Official Source

Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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