HERizon-Breast: A ctDNA-Guided Adaptive Study of Sequential Anti-HER2 Therapies and CNS Prophylaxis to Induce Long-Term Remission
1 other identifier
interventional
60
1 country
7
Brief Summary
Thie purpose of this study is to find out whether a personalized treatment approach-using a series of ctDNA tests along with standard imaging scans to help decide when to step up (escalate) or decrease (de-escalate) sequential treatments (given one after another)-combined with local therapies (which treat cancer in a specific part of the body) and treatments that prevent cancer from spreading to the central nervous system (CNS; including the brain and spinal cord) can result in long-lasting remission and possibly cure some participants with HER2+ metastatic breast cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 breast-cancer
Started Mar 2026
Typical duration for phase_2 breast-cancer
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 4, 2026
CompletedFirst Submitted
Initial submission to the registry
March 5, 2026
CompletedFirst Posted
Study publicly available on registry
March 10, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 4, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 4, 2030
May 22, 2026
May 1, 2026
4 years
March 5, 2026
May 20, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Proportion of participants who maintain Complete Response/CR and Molecular Complete Response/mCR
To evaluate the proportion of participants who maintain CR and mCR for 12 months from initiation of the maintenance/surveillance phase.
12 months
Study Arms (1)
Participants with Stage IV Breast Cancer
EXPERIMENTALMale or female participants who are ≥18 years old with histologically confirmed diagnosis of unresectable locally advanced or metastatic breast cancer/MBC
Interventions
The use of this assay is expected to optimize treatment without introducing significant new risks or deviating from approved therapeutic protocols.
The use of this assay is expected to optimize treatment without introducing significant new risks or deviating from approved therapeutic protocols.
T-DXd is a HER2-targeting antibody drug conjugate that consists of an anti-HER2 antibody.
Eligibility Criteria
You may qualify if:
- Male or female participants who are ≥18 years old with histologically confirmed diagnosis of unresectable locally advanced or MBC.
- Stage IV at the diagnosis (i.e., de novo metastatic) as per AJCC 8.
- HER2 IHC results of 3+.
- Life expectancy of ≥12 weeks.
- Must be deemed medically fit for surgery and be surgical candidates upfront, or potentially operable if there is response to induction therapy.
- Must have measurable disease per PERCIST 1.0.
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 14 days prior to the start of study intervention.
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), as described in Appendix 3 during the intervention period. The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study intervention.
- A WOCBP must have a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin \[β-hCG\]) within 72 hours before the first dose of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dose of therapy.
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below:
- Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
- +11 more criteria
You may not qualify if:
- Patients diagnosed with HER2+ breast cancer as per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines with HER2 IHC results of 1-2+ and positive FISH or ISH
- Prior exposure to anti-HER2 therapy of any kind or any systemic anti-cancer treatment of any kind for breast cancer.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 2 weeks prior to the first dose of study intervention.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in doses \>10 mg daily of oral prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Inhaled, intranasal, intra-articular, or topical steroid use are allowed.
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, which have undergone potentially curative therapy are not excluded.
- Has known CNS metastases and/or leptomeningeal carcinomatosis.
- Has a history or evidence of active pneumonitis or interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Has grade \>=3 neuropathy of any etiology.
- Has an active infection requiring antibiotics.
- Has a known history of Human Immunodeficiency Virus (HIV) infection.
- Has an inability to swallow capsules or tablets.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
- Has had an allogenic tissue/solid organ transplant.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering at Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering at Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)
Commack, New York, 11725, United States
Memorial Sloan Kettering at Westchester (Limited Protocol Activities)
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center (All Protocol Activites)
New York, New York, 10065, United States
Memorial Sloan Kettering at Nassau (Limited Protocol Activities)
Uniondale, New York, 11553, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Pedram Razavi, MD, PhD
Memorial Sloan Kettering Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 5, 2026
First Posted
March 10, 2026
Study Start
March 4, 2026
Primary Completion (Estimated)
March 4, 2030
Study Completion (Estimated)
March 4, 2030
Last Updated
May 22, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made following one year after publication and for up to 36 months later. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.