Breast CancerPhase 2NCT07459673
HERizon-Breast: A ctDNA-Guided Adaptive Study of Sequential Anti-HER2 Therapies and CNS Prophylaxis to Induce Long-Term Remission
A Phase 2 study testing Personalis NeXT Personal, Natera Signatera and fam-trastuzumab deruxtecan-nxki (T-DXd) in people with Breast Cancer and HER2-positive Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, HER2-positive Breast Cancer, Breast Cancer Stage IV
- What is being tested?
- Personalis NeXT Personal, Natera Signatera and fam-trastuzumab deruxtecan-nxki (T-DXd)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 7 sitesUnited States
- Study dates
- 4 Mar 2026to 4 Mar 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Additional requirements for pregnancy testing during and after study intervention are located in Appendix 2.The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
- 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.
- Criteria for known Hepatitis B and C positive subjects: Hepatitis B and C screening tests are required as per MSK policy but do not need to be repeated prior to study unless there is a known history of Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection.
- Participants who have active hepatitis B infection (defined as HBsAg positive and/or detectable HBV DNA) are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. Participants should remain on anti-viral therapy throughout study intervention and follow MSK guidelines for HBV anti-viral therapy post completion of study intervention.
- Participants with a history of HCV infection (defined as anti-HCV Ab positive and detectable HCV RNA) are eligible if HCV viral load is undetectable at screening.
- Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.
- Table 1 Adequate Organ Function Laboratory Values Hematological Absolute neutrophil count (ANC): ≥1500/µL Platelets: ≥100 000/µL Hemoglobin: ≥9.0 g/dL or ≥5.6 mmol/L
- Renal Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl): ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × ULN
- Hepatic Total bilirubin: ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN AST (SGOT) and ALT (SGPT)
- Coagulation
- International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT):
- ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
- ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal. a Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks. b Creatinine clearance (CrCl) should be calculated per institutional standard. Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.
Who cannot join
- 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.
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- 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.
- Has significant cardiovascular impairment within 12 months of the first dose of study drug: such as NYHA Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted.
- Has a left ventricular ejection fraction (LVEF) below the institutional normal range of 50%, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO).
- Known intolerance to any of the study drugs (or any of the excipients).
- Has had major surgery within 3 weeks prior to first dose of study interventions. Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
United States7 sites, 7 recruiting
- Recruiting
Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920
Pedram Razavi, MD, PhD, 646-888-4821
- Recruiting
Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)
Commack, New York, 11725
Pedram Razavi, MD, PhD, 646-888-4821
- Recruiting
Memorial Sloan Kettering at Westchester (Limited Protocol Activities)
Harrison, New York, 10604
Pedram Razavi, MD, PhD, 646-888-4821
- Recruiting
Memorial Sloan Kettering at Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748
Pedram Razavi, MD, PhD, 646-888-4821
- Recruiting
Memorial Sloan Kettering at Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645
Pedram Razavi, MD, PhD, 646-888-4821
- Recruiting
Memorial Sloan Kettering Cancer Center (All Protocol Activites)
New York, New York, 10065
Pedram Razavi, MD, PhD, 646-888-4821
- Recruiting
Memorial Sloan Kettering at Nassau (Limited Protocol Activities)
Uniondale, New York, 11553
Pedram Razavi, MD, PhD, 646-888-4821
About this study
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.
- Being tested
- Personalis NeXT Personal, Natera Signatera, fam-trastuzumab deruxtecan-nxki (T-DXd), pertuzumab, called T-DXd+P
- Keywords
- breast cancer, HER2-positive Breast Cancer, Breast Cancer Stage IV, Memorial Sloan Kettering Cancer Center, 25-258
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Personalis NeXT PersonalDiagnostic test
The use of this assay is expected to optimize treatment without introducing significant new risks or deviating from approved therapeutic protocols.
Natera SignateraDiagnostic test
The use of this assay is expected to optimize treatment without introducing significant new risks or deviating from approved therapeutic protocols.
fam-trastuzumab deruxtecan-nxki (T-DXd)Drug
T-DXd is a HER2-targeting antibody drug conjugate that consists of an anti-HER2 antibody.
pertuzumab, called T-DXd+PDrug
intravenous (IV) infusion
| Study group | Role | What they receive |
|---|---|---|
| Participants with Stage IV Breast Cancer | Experimental | Male or female participants who are ≥18 years old with histologically confirmed diagnosis of unresectable locally advanced or metastatic breast cancer/MBC Receives: Diagnostic Test: Personalis NeXT Personal; Diagnostic Test: Natera Signatera; Drug: fam-trastuzumab deruxtecan-nxki (T-DXd); Drug: pertuzumab, called T-DXd+P |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2026
- Study start4 Mar 2026
- Primary completion4 Mar 2030 (estimated)
- Study completion4 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pedram Razavi, MD, PhD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07459673
- Sponsor's protocol ID
- 25-258
- Status last verified
- Aug 2026
- First submitted
- 5 Mar 2026
- Last updated
- 20 Aug 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HERizon-Breast: A ctDNA-Guided Adaptive Study of Sequential Anti-HER2 Therapies and CNS Prophylaxis to Induce Long-Term Remission
- ClinicalTrials.gov ID
- NCT07459673
- Acronym / sponsor ID
- 25-258
- Keywords
- breast cancer, HER2-positive Breast Cancer, Breast Cancer Stage IV, Memorial Sloan Kettering Cancer Center, 25-258
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- 4 Mar 2026 (actual)
- Primary completion
- 4 Mar 2030 (estimated)
- Study completion
- 4 Mar 2030 (estimated)
- First posted
- 10 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants with Stage IV Breast Cancer | Experimental | Diagnostic Test: Personalis NeXT Personal, Diagnostic Test: Natera Signatera, Drug: fam-trastuzumab deruxtecan-nxki (T-DXd), Drug: pertuzumab, called T-DXd+PMale or female participants who are ≥18 years old with histologically confirmed diagnosis of unresectable locally advanced or metastatic breast cancer/MBC |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Personalis NeXT PersonalThe use of this assay is expected to optimize treatment without introducing significant new risks or deviating from approved therapeutic protocols. | Diagnostic test | Participants with Stage IV Breast Cancer |
| Natera SignateraThe use of this assay is expected to optimize treatment without introducing significant new risks or deviating from approved therapeutic protocols. | Diagnostic test | Participants with Stage IV Breast Cancer |
| fam-trastuzumab deruxtecan-nxki (T-DXd)T-DXd is a HER2-targeting antibody drug conjugate that consists of an anti-HER2 antibody. | Drug | Participants with Stage IV Breast Cancer |
| pertuzumab, called T-DXd+Pintravenous (IV) infusion | Drug | Participants with Stage IV Breast Cancer |
Primary outcome
Proportion of participants who maintain Complete Response/CR and Molecular Complete Response/mCR
Time frame: 12 months
To evaluate the proportion of participants who maintain CR and mCR for 12 months from initiation of the maintenance/surveillance phase.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2026.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Pedram Razavi, MD, PhD principal investigator
Memorial Sloan Kettering Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Personalis NeXT Personal, Natera Signatera and fam-trastuzumab deruxtecan-nxki (T-DXd) in people with Breast Cancer and HER2-positive Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Pedram Razavi, MD, PhD (646-888-4821, razavip@mskcc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants who maintain Complete Response/CR and Molecular Complete Response/mCR (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2026; AzTrials last refreshed its copy on 6 Nov 2026.