Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1
124 participants
INTERVENTIONAL
2023-02-15
2029-12-30
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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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.
ALX148
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.
Fam-Trastuzumab Deruxtecan-Nxki
Antibody-drug conjugate (ADC): A recombinant humanized anti-human HER2 IgG1 monoclonal antibody, conjugated with linker to a Topoisomerase I inhibitor
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.
Zanidatamab
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).
Tucatinib
Small molecule tyrosine kinase inhibitor (TKI) of HER2 (oral drug).
Interventions
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ALX148
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.
Fam-Trastuzumab Deruxtecan-Nxki
Antibody-drug conjugate (ADC): A recombinant humanized anti-human HER2 IgG1 monoclonal antibody, conjugated with linker to a Topoisomerase I inhibitor
Zanidatamab
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).
Tucatinib
Small molecule tyrosine kinase inhibitor (TKI) of HER2 (oral drug).
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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.
Exclusion Criteria
* 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. Newly discovered asymptomatic lesions that are not life threatening and do not require urgent local treatment to ensure patient safety, after consultation with study regimen chaperones, may be 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.
* 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 subjects, or affect the endpoints of the trial.
18 Years
ALL
No
Sponsors
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QuantumLeap Healthcare Collaborative
OTHER
Responsible Party
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Principal Investigators
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Paula R Pohlmann, MD, MSc, PhD
Role: PRINCIPAL_INVESTIGATOR
M.D. Anderson Cancer Center
Locations
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The University of Alabama at Birmingham O'Neal Comprehensive Cancer Center
Birmingham, Alabama, 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
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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I-SPY-P1
Identifier Type: -
Identifier Source: org_study_id
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