The SAPPHO Study: Sequential Therapy With Curative Intent in de Novo HER2+ Metastatic Breast Cancer

Recruiting now · Phase 2

Conditions studied: Breast Cancer Female, Breast Cancer, Breast Cancer Metastatic, Estrogen Receptor-positive Breast Cancer, HER2-positive Breast Cancer, Stage IV Breast Cancer

In brief

The purpose of this study is to test the safety and effectiveness of a sequence of drugs (a Taxane plus Trastuzumab plus Pertuzumab followed by Trastuzumab Deruxtecan, followed by Tucatinib plus Ado-Trastuzumab Emtansine (T-DM1), followed by Trastuzumab plus Pertuzumab plus Tucatinib) in HER2+ Breast Cancer. The study will help investigators understand whether first intensifying therapy for a specific period and then stopping treatment is safe and effective for participants. The names of the study drugs involved in this study are: * Paclitaxel (a type of anti-microtubule agent) * Docetaxel (a type of anti-microtubule agent) * Nab-Paclitaxel (a type of anti-microtubule agent) * Trastuzumab (a type of IgG1 kappa monoclonal antibody) * Pertuzumab (a type of monoclonal antibody) * Trastuzumab Deruxtecan (a type of HER2-directed antibody drug conjugate) * Tucatinib (Tyrosine Kinase HER2 Inhibitor) * Ado-trastuzumab emtansine or T-DM1 (a type of HER2-targeted antibody-drug conjugate)

Key facts

Study ID

NCT06439693

Run by

Dana-Farber Cancer Institute

People needed

72

Starts

2024-08-08

Expected to finish

2033-03-30

Last updated by the study team

2026-08-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must have histologically or cytologically confirmed unresectable locally advanced or metastatic invasive breast carcinoma. Patients must have stage IV breast carcinoma at diagnosis (i.e., de novo metastatic) with unequivocal evidence of metastasis on imaging.
• Diagnosis of HER2-positive invasive breast carcinoma and 3+ by immunohistochemistry on both breast and metastatic biopsies, as defined by the current American Society of Clinical Oncology - College of American Pathologists (ASCO/CAP) guidelines. HER2 status must be determined at a Clinical Laboratory Improvements Amendments (CLIA)-certified or International Organization for Standardization (ISO)-accredited laboratory (central testing not required). Patients with HER2 1+ or 2+ disease which is HER2 FISH positive are not eligible to enroll.
• No prior systemic therapy for invasive breast cancer, aside from first-line trastuzumab/pertuzumab/taxane (THP) within 6 weeks from treatment start. Prior endocrine therapy for non-invasive breast carcinoma or non-cancerous lesions is allowed if it has been completed at least 5 years prior to study entry.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of trastuzumab, pertuzumab, paclitaxel, trastuzumab deruxtecan, T-DM1 and tucatinib in Participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1
• Left ventricular ejection fraction (LVEF) ≥50%, as assessed by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) documented within 12 weeks prior to first dose of study treatment, or within 12 weeks before starting THP for patients who start metastatic therapy prior to study entry.
• Participants must meet the following organ and marrow function as defined below within 28 days prior to registration:
• Hgb ≥9.0 g/dL
• Absolute Neutrophil Count ≥ 1,000 /mm3
• Platelets ≥100,000/mm3
• Total bilirubin ≤ 1.5 x ULN (institutional) or direct bilirubin within normal limits in patients with a history of Gilbert\'s syndrome.
• AST and ALT ≤ 2.5 x ULN (institutional) or ≤ 5 x ULN for participants with documented liver metastases
• Serum creatinine ≤ 1.5 x ULN (institutional) OR calculated GFR ≥60mL/min
• Participants with concurrent human immunodeficiency virus (HIV) infection are eligible provided the following criteria are met:
• CD4+ T-cell (CD4+) counts \> 350 cells/uL
• No history of AIDS-defining opportunistic infection within 12 months prior to enrollments
• Any medication used in an ART regimen must have no known interaction with the agents used in the study treatment regimen.
• Participants with active or chronic Hepatitis B or C are eligible provided they meet the liver function criteria described in 3.1.7 and are not on a medication with a known liver function criteria described in 3.1.7 and are not on a medication with a known interaction with the agents used in the study treatment regimen. The following guidance applies:
• patients with chronic HBV infection with active disease who meet the FDA criteria for anti-HBV therapy should be on a suppressive antiviral therapy prior to initiation of cancer therapy.
• patients with a history of HCV infection should have completed curative antiviral treatment. HCV viral load must be below the limit of quantification.
• patients who are HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution are eligible.
• Participants with brain metastases identified at diagnosis or at time of screening are eligible if the following criteria are met:
• Known, untreated brain metastases must undergo definitive local therapy - as determined by treating physician - prior to study entry.
• Treated brain metastases must be clinically stable since treatment. Restaging brain MRI is not required to deem eligibility if local therapy was given within 28 days from first dose of study treatment. Patients are eligible if time from local therapy and first dose of study treatment is:
• 7 days for stereotactic radiosurgery (SRS);

You may not qualify if…

• Prior history of invasive breast carcinoma
• Treatment with any other investigational agents for this condition.
• Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 28 days of study entry or an anticipated need for major surgery during the study.
• Extracranial palliative radiotherapy within 7 days prior to enrollment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to trastuzumab, pertuzumab, paclitaxel, trastuzumab deruxtecan, trastuzumab emtansine, tucatinib.
• Participants with a medical history of myocardial infarction within 6 months before enrollment or symptomatic CHF (NYHA Class II to IV).
• Subjects must not have any of the following:
• Any untreated brain lesion on screening MRI, unless approved by the Sponsor Investigator
• Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of \>2 mg of dexamethasone (or equivalent).
• Known or concurrent leptomeningeal disease on screening MRI
• Poorly controlled (\>1/week) generalized or complex partial seizures
• History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted upon discussion with the Sponsor-Investigator.
• History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• History of other lung disease, such as:
• Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months of study enrolment, severe asthma, severe chronic obstructive pulmonary disorder (COPD), restrictive lung disease, pleural effusion etc.).
• Any autoimmune, connective tissue or inflammatory disorders (e.g., rheumatoid arthritis, Sjogren's, sarcoidosis, etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening.
• Prior pneumonectomy.
• Active or uncontrolled clinically serious infection
• Have inability to swallow pills or significant gastrointestinal disease which would preclude the adequate oral absorption of medications
• Have ongoing ≥ Grade 2 diarrhea of any etiology
• Participants receiving any medications or substances that are inhibitors or inducers of CYP2C8 and/or CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference.
• Pregnant women are excluded from this study because of potential for teratogenic or abortifacient effects of study drugs. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with study drugs, breastfeeding should be discontinued prior to enrollment.

Where it is running

• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)

Full record on ClinicalTrials.gov

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