PRE-Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis: A Phase I/Ib Platform Trial
Summary
I-SPY Phase I/Ib (I-SPY-P1) is an open-label, multisite platform study designed to evaluate single agents or combinations in a metastatic treatment setting that may be relevant for breast cancer patients with the overall goal of moving promising drug regimens into the I-SPY 2 SMART Design Trial (NCT01042379) and/or other oncology-based trials in a timely manner.
Detailed description
The PRE-I-SPY/I-SPY-P1 study is a platform trial with multiple ongoing drug regimen arms. In most cases, the treatment arm will have a dose-finding group (Part 1) and a dose-expansion group (Part 2). Eligibility criteria will vary according to the experimental regimen. Participant eligibility may vary according to the arm or the part within the study arm, including with respect to diagnosis. Arms could include participants diagnosed with certain solid tumors or specifically with breast cancer. Arms may restrict enrollment to a certain molecular pathway abnormality or histologic diagnosis. The trial allows for various study arm designs, with the goal to complete analysis of a study arm in 12 to 18 months.
Arms & interventions
- DrugALX148
CD47 Inhibitor: A fusion protein containing a high affinity engineered D1 domain of human signal regulatory protein alpha (SIRPα) variant 1 (v1) genetically linked to a modified and inactive Fc domain of human immunoglobulin (Ig) G1.
- DrugFam-Trastuzumab Deruxtecan-Nxki
Antibody-drug conjugate (ADC): A recombinant humanized anti-human HER2 IgG1 monoclonal antibody, conjugated with linker to a Topoisomerase I inhibitor
- DrugZanidatamab
Bispecific HER2 antibody: A humanized, bispecific, immunoglobulin G isotype 1 (IgG1)-like antibody directed against the juxtamembrane extracellular domain (ECD4) and the dimerization domain (ECD2) of human epidermal growth factor receptor 2 (HER2).
- DrugTucatinib
Small molecule tyrosine kinase inhibitor (TKI) of HER2 (oral drug).
Outcome measures
Primary
Incidence of Adverse Events related to the treatment
Evaluate the number of adverse events related to the treatment according to the current version of CTCAE during the trial.
Time frame: Start of treatment to 30 days post treatment (estimated 12 -18 months)
Incidence of Dose Limiting Toxicities (DLTs) at each dose level
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).
Time frame: DLT observation period: Start of treatment to 21 days (Cycle 1)
Maximum Tolerated Dose (MTD)
The maximum dose level (mg/kg) which is not eliminated.
Time frame: Start of treatment to the date of last participant at end of DLT observation period at highest dose level (estimated 6 months)
Recommended Phase 2 Dose (RP2D)
Using all available data, computation of RP2D (mg/kg), which may not be the MTD.
Time frame: Start of treatment to the date of last participant at highest dose level (estimated 6 months)
Overall Response Rate (ORR)
To obtain preliminary efficacy data of the new agents/regimens in participants with certain advanced solid tumors and breast cancer.
Time frame: Start of treatment to 12 months
Duration of Response (DOR)
To obtain preliminary efficacy data of the new agents/regimens in participants with certain advanced solid tumors and breast cancer.
Time frame: Start of treatment to 12 months
Secondary
Progression Free Survival (PFS) - descriptive
Time frame: Start of treatment to 12 months
Clinical Benefit Rate (CBR) at 6 months
Time frame: Start of treatment to 6 months
Eligibility criteria
Study locations (7)
The University of Alabama at Birmingham O'Neal Comprehensive Cancer Center
Birmingham, Alabama, 35233
Moffitt Cancer Center
Tampa, Florida, 33612
The University of Chicago Medicine Comprehensive Cancer Center
Chicago, Illinois, 60637
UChicago Medicine Comprehensive Cancer Center at Silver Cross Hospital
New Lenox, Illinois, 60451
UChicago Medicine Orland Park
Orland Park, Illinois, 60462
University of Minnesota Masonic Cancer Center
Minneapolis, Minnesota, 55455
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030