PRE-ISPY Phase I/II Oncology Platform Program (PRE-ISPY)

August 31, 2026 updated by: QuantumLeap Healthcare Collaborative

PRE-Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis: A Phase I/II Platform Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

280

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • The University of Alabama at Birmingham O'Neal Comprehensive Cancer Center
        • Principal Investigator:
          • Erica Stringer-Reasor, MD
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Nusrat Jahan, MD
        • Sub-Investigator:
          • Gabrielle Rocque, MD
        • Sub-Investigator:
          • Midhun Malla, MD
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Not yet recruiting
        • Mayo Clinic Comprehensive Cancer Center
        • Sub-Investigator:
          • Mojun Zhu, MD
        • Contact:
        • Sub-Investigator:
          • Lida Mina, MD
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Active, not recruiting
        • University of Colorado Cancer Center
    • Florida
      • Tampa, Florida, United States, 33612
        • Active, not recruiting
        • Moffitt Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • The University of Chicago Medicine Comprehensive Cancer Center
        • Principal Investigator:
          • Nan Chen, MD
        • Sub-Investigator:
          • Rita Nanda, MD
        • Contact:
        • Sub-Investigator:
          • Ardaman Shergill, MD, MSPH
      • New Lenox, Illinois, United States, 60451
        • Recruiting
        • UChicago Medicine Comprehensive Cancer Center at Silver Cross Hospital
        • Principal Investigator:
          • Nan Chen, MD
        • Contact:
      • Orland Park, Illinois, United States, 60462
        • Recruiting
        • UChicago Medicine Orland Park
        • Principal Investigator:
          • Nan Chen, MD
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • University of Minnesota Masonic Cancer Center
        • Principal Investigator:
          • David Potter, MD, PhD
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Anne Blaes, MD, MS
        • Sub-Investigator:
          • Emil Lou, MD, PhD
      • Rochester, Minnesota, United States, 55905
        • Not yet recruiting
        • Mayo Clinic Comprehensive Cancer Center
        • Sub-Investigator:
          • Zhaohui Jin, MD
        • Contact:
        • Principal Investigator:
          • Roberto A Leon-Ferre, MD
    • Texas
      • Houston, Texas, United States, 77030
        • Active, not recruiting
        • The University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: 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;
Other Names:
  • Evorpacept
Drug: Fam-Trastuzumab Deruxtecan-Nxki
5.4 mg/kg IV Q3W; allowed to dose reduce after DLT observation period
Other Names:
  • 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.
Drug: Zanidatamab
20 mg/kg IV Q2W on Day 1 and Day 15 of each 28 day cycle
Other Names:
  • ZW25
  • zani
  • Ziihera
Drug: Tucatinib
Dose Level 1: 300 mg PO BID daily; Dose Leve Minus 1: 250 mg PO BID daily
Other Names:
  • 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.
Drug: TTX-MC138
4.8 mg/kg Q4W IV on Day 1 for up to 12 cycles as interception therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: 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)
Time Frame: 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
Incidence of Adverse Events related to the treatment
Time Frame: 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
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS) - descriptive
Time Frame: 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
Time Frame: 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

QuantumLeap Healthcare Collaborative

Collaborators

Pfizer
Jazz Pharmaceuticals
ALX Oncology Inc.
TransCode Therapeutics

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 15, 2023

Primary Completion (Estimated)

December 30, 2030

Study Completion (Estimated)

December 30, 2031

Study Registration Dates

First Submitted

April 22, 2022

First Submitted That Met QC Criteria

May 10, 2023

First Posted (Actual)

May 22, 2023

Study Record Updates

Last Update Posted (Actual)

September 2, 2026

Last Update Submitted That Met QC Criteria

August 31, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • I-SPY-P1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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