Trial Title:
PRE-I-SPY Phase I/Ib Oncology Platform Program
NCT ID:
NCT05868226
Condition:
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
Conditions: Official terms:
Carcinoma
Breast Neoplasms
Triple Negative Breast Neoplasms
Trastuzumab
Tucatinib
Trastuzumab deruxtecan
Conditions: Keywords:
I-SPY Trials
Quantum Leap Healthcare Collaborative
QLHC
I-SPY
I-SPY2
I-SPY1
PRE-ISPY
PRE-I-SPY
I-SPY Phase 1
I-SPY Phase 1b
I-SPY-P1
ISPY
ISPYP1
I-SPY Phase 1 Platform
ISPY2
ISPY1
Phase 1 Platform
Phase 1 Oncology Platform
T-DXd naive
PRE1
PRE2
PRE3
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Intervention model description:
This is an open-label, multi-site, multi-arm platform study, where each drug regimen arm
may have different study designs and eligibility. In particular, dose finding parts may
employ different designs (e.g., 3+3, Bayesian Optimal Interval Design [BOIN], continual
reassessment method [CRM], etc.) for each arm in the PRE-I-SPY program. See each arm for
specific study model details.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
ALX148
Description:
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.
Arm group label:
PRE1 ALX148 (Evorpacept) + Fam-Trastuzumab Deruxtecan-Nxki (T-DXd, Enhertu®)
Other name:
Evorpacept
Intervention type:
Drug
Intervention name:
Fam-Trastuzumab Deruxtecan-Nxki
Description:
Antibody-drug conjugate (ADC): A recombinant humanized anti-human HER2 IgG1 monoclonal
antibody, conjugated with linker to a Topoisomerase I inhibitor
Arm group label:
PRE1 ALX148 (Evorpacept) + Fam-Trastuzumab Deruxtecan-Nxki (T-DXd, Enhertu®)
Other name:
Enhertu
Other name:
T-DXd
Intervention type:
Drug
Intervention name:
Zanidatamab
Description:
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).
Arm group label:
PRE2 Zanidatamab (ZW25, zani) + Tucatinib (TUKYSA®)
Other name:
ZW25
Other name:
zani
Intervention type:
Drug
Intervention name:
Tucatinib
Description:
Small molecule tyrosine kinase inhibitor (TKI) of HER2 (oral drug).
Arm group label:
PRE2 Zanidatamab (ZW25, zani) + Tucatinib (TUKYSA®)
Other name:
TUKYSA
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.
Criteria for 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 (freshly cut 14 unstained
tumor slides would be acceptable).
- 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
- 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: No other anticancer therapy within the following periods:
- chemotherapy or investigational agents, 3 weeks
- mitomycin C and nitrosoureas, 6 weeks
- radiotherapy, 3 weeks
- 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,
pulmonary embolism 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.
- 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.
- Additional arm specific exclusion criteria as needed by drug arm regimen
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The University of Alabama at Birmingham O'Neal Comprehensive Cancer Center
Address:
City:
Birmingham
Zip:
35233
Country:
United States
Status:
Recruiting
Contact:
Last name:
Anethea Tolliver
Phone:
205-644-9896
Email:
anetheatolliver@uabmc.edu
Contact backup:
Last name:
Lindsey M Waldheim
Email:
lwaldheim@uabmc.edu
Investigator:
Last name:
Erica Stringer-Reasor, MD
Email:
Principal Investigator
Investigator:
Last name:
Nusrat Jahan, MD
Email:
Sub-Investigator
Investigator:
Last name:
Katia Khoury, MD
Email:
Sub-Investigator
Investigator:
Last name:
Gabrielle Rocque, MD
Email:
Sub-Investigator
Facility:
Name:
The University of Chicago Medicine Comprehensive Cancer Center
Address:
City:
Chicago
Zip:
60637
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clara Duarte
Phone:
773-834-5727
Email:
vqq5698@bsd.uchicago.edu
Investigator:
Last name:
Nan Chen, MD
Email:
Principal Investigator
Investigator:
Last name:
Rita Nanda, MD
Email:
Sub-Investigator
Facility:
Name:
UChicago Medicine Comprehensive Cancer Center at Silver Cross Hospital
Address:
City:
New Lenox
Zip:
60451
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clara Duarte
Phone:
773-834-5727
Email:
vqq5698@bsd.uchicago.edu
Investigator:
Last name:
Nan Chen, MD
Email:
Principal Investigator
Facility:
Name:
UChicago Medicine Orland Park
Address:
City:
Orland Park
Zip:
60462
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clara Duarte
Phone:
773-834-5727
Email:
vqq5698@bsd.uchicago.edu
Investigator:
Last name:
Nan Chen, MD
Email:
Principal Investigator
Facility:
Name:
University of Minnesota Masonic Cancer Center
Address:
City:
Minneapolis
Zip:
55455
Country:
United States
Status:
Recruiting
Contact:
Last name:
Katie Vaughn, RN
Phone:
612-624-6968
Email:
schro811@umn.edu
Contact backup:
Last name:
Erin Rogers
Email:
roge0507@umn.edu
Investigator:
Last name:
David Potter, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Doug Yee, MD
Email:
Sub-Investigator
Facility:
Name:
The University of Texas MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Heather Walker, MPH, CCRP
Phone:
832-564-8343
Email:
HKWalker@mdanderson.org
Contact backup:
Last name:
Julia Moore, RN
Email:
jmoore@mdanderson.org
Investigator:
Last name:
Paula R Pohlmann, MD, MSc, PhD
Email:
Principal Investigator
Investigator:
Last name:
Debasish Tripathy, MD
Email:
Principal Investigator
Investigator:
Last name:
Funda Meric-Bernstam, MD
Email:
Sub-Investigator
Investigator:
Last name:
Jason A Mouabbi, MD
Email:
Sub-Investigator
Investigator:
Last name:
Bora Lim, MD
Email:
Sub-Investigator
Investigator:
Last name:
Ecaterina E Dumbrava, MD
Email:
Sub-Investigator
Start date:
December 22, 2022
Completion date:
December 30, 2027
Lead sponsor:
Agency:
QuantumLeap Healthcare Collaborative
Agency class:
Other
Source:
QuantumLeap Healthcare Collaborative
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05868226
