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Clinical trial Recruiting at 1 site Phase 2 Interventional Ages 18 and up

Adjunct Therapy De-escalation in Early HER2+ and TNBC After Neoadjuvant Response

Official title: Optimization of Adjuvant Systemic Therapy in Patients With Early HER2-Positive (HER2+) Breast Cancer or Triple Negative Breast Cancer (TNBC) That Achieved a Pathological Complete Response (pCR) After Neoadjuvant Systemic Therapy and Do Not Have Molecular Residual Disease (MRD-Negative): A Phase II Clinical Trial (The MolecularPCR Trial)

Run by M.D. Anderson Cancer Center · NCT07407920 · Data updated 2026-11-12

This phase 2 trial tests stopping certain post-surgery immunotherapy and targeted therapies early in people with early HER2+ or triple-negative breast cancer who have no detectable cancer DNA after neoadjuvant treatment and surgery.

Quick facts

PhasePhase 2
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment120 (estimated)
SponsorM.D. Anderson Cancer Center
Academic / other
Drugs / interventionstrastuzumab, pertuzumab, pembrolizumab, chemotherapy, cyclophosphamide, doxorubicin, Immunotherapy
Locations1 site (Houston, Texas)
StatusRecruiting
StartedOctober 9, 2025
Main results expectedSeptember 30, 2028
Study endsSeptember 30, 2028
Registry record updatedNovember 3, 2026
Trial IDNCT07407920 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Adults with early-stage HER2-positive or early-stage TNBC who achieve a pathologic complete response after neoadjuvant therapy and are MRD-negative by NeXT Personal assay 4–6 weeks after surgery.

Probably not a fit

Patients who do not achieve MRD negativity or who relapse early may not benefit from de-escalated adjuvant therapy.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a phase II interventional trial evaluating de-escalation of adjuvant therapy in patients with early-stage HER2-positive or triple-negative breast cancer who achieve a pathologic complete response after neoadjuvant therapy and are MRD-negative by the NeXT Personal assay. Primary goals are to measure 3-year event-free survival after surgery when SOC adjuvant pembrolizumab (TNBC) or trastuzumab/pertuzumab (HER2+) is discontinued following MRD negativity. Secondary aims include tracking ctDNA conversion from negative to positive during de-escalation, and characterizing the prevalence of pCR with positive MRD post-surgery. Interventions include biospecimen collection and administration of pembrolizumab, pertuzumab, trastuzumab as part of the protocol framework. Locations are limited to MD Anderson Cancer Center in Houston, TX.

Why it matters

Potential benefit: If successful, patients may avoid unnecessary adjuvant therapy without compromising long-term outcomes.

How similar studies have gone: Prior studies in de-escalation strategies for select breast cancer patients have shown promise, but this precise MRD-guided approach is exploratory.

Who can join: the full rules

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* EARLY HER2 POSITIVE (+) BREAST CANCER COHORT: Female or male with a diagnosis of biopsy proven invasive breast cancer HER2+, hormone (estrogen and progesterone)-receptor positive or negative. The HER2 status (following American Society of Clinical Oncology \[ASCO\]/College of American Pathologists \[CAP\] guidelines) and hormone-receptor status will be determined according to institutional (local) guidelines
* EARLY TNBC COHORT: Female or male with a diagnosis of biopsy proven invasive TNBC (estrogen and progesterone receptor \< 10%). The HER2 status (following ASCO/CAP guidelines) and hormone-receptor status will be determined according to institutional (local) guidelines
* FOR BOTH HER2+ AND TNBC COHORTS: Invasive breast cancer of any tumor histologic grade and/or nuclear grade, and any tumor histological subtype including but not limited to infiltrating ductal carcinoma, infiltrating lobular carcinoma, mucinous carcinoma, papillary carcinoma, tubular carcinoma, metaplastic carcinoma, and mixed histology
* FOR BOTH HER2+ AND TNBC COHORTS: Clinical tumor stage (per American Joint Committee on Cancer \[AJCC\] 8th edition): T1-4, N0-2a, M0. Patients who have a diagnosis of inflammatory breast cancer are eligible. Patients should not have clinical evidence of locoregional or distant metastatic breast cancer
* EARLY HER2+ BREAST CANCER COHORT: Have completed NST with a trastuzumab plus pertuzumab and chemotherapy-based regimen (for example, docetaxel plus minus carboplatin plus trastuzumab plus pertuzumab known as the docetaxel/pertuzumab/trastuzumab \[THP\]/carboplatin/paclitaxel/pertuzumab/trastuzumab \[TCHP\] regimens) followed by definitive breast surgery where the surgical pathology reports a pCR (ypT0-Tis, ypN0) and are willing to discontinue adjuvant trastuzumab plus pertuzumab
* EARLY TNBC COHORT: Have completed NST with a pembrolizumab plus chemotherapy-based regimen (for example, the KEYNOTE-522 regimen which is paclitaxel plus carboplatin plus pembrolizumab followed by doxorubicin plus cyclophosphamide plus pembrolizumab) followed by definitive breast surgery where the surgical pathology reports a pCR (ypT0-Tis, ypN0) and are willing to discontinue adjuvant pembrolizumab
* The surgical pathology report needs to show a pCR (ypT0-Tis, ypN0) for a patient to be able to participate in this study and all enrolled patients should be willing to discontinue standard adjuvant systemic therapy
* FOR BOTH HER2+ AND TNBC COHORTS: Adequate archival tumor tissue from the core diagnostic biopsy (per Personalis)
* FOR BOTH HER2+ AND TNBC COHORTS: Age ≥ 18 years
* FOR BOTH HER2+ AND TNBC COHORTS: Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
* FOR BOTH HER2+ AND TNBC COHORTS: Absolute neutrophil count ≥ 1,000/mcL
* FOR BOTH HER2+ AND TNBC COHORTS: Hemoglobin ≥ 9.0 g/dL
* FOR BOTH HER2+ AND TNBC COHORTS: Platelets ≥ 100,000/mcL
* FOR BOTH HER2+ AND TNBC COHORTS: Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN); patients with Gilbert's syndrome (if direct bilirubin \<1.5 x institutional ULN)
* FOR BOTH HER2+ AND TNBC COHORTS: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN
* FOR BOTH HER2+ AND TNBC COHORTS: Creatinine ≤ 1.5 mg/dL
* FOR BOTH HER2+ AND TNBC COHORTS: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* FOR BOTH HER2+ AND TNBC COHORTS: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* FOR BOTH HER2+ AND TNBC COHORTS: Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible
* FOR BOTH HER2+ AND TNBC COHORTS: Pre- and postmenopausal women are eligible
* FOR BOTH HER2+ AND TNBC COHORTS: Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Patients with tumor stage of cN2b or cN3 are not eligible
* History of other malignancies besides breast cancer within the past 5 years, except cervical cancer in situ, melanoma in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin
* Patients who are receiving any other anti-cancer investigational agents
* Patients with known cancer metastases from any site
* Patients with uncontrolled intercurrent illness including but not limited to active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic cardiac arrythmias
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* Blood transfusion within 2 weeks before collection of blood for ctDNA testing
* Patients who have received 4 or more cycles of SOC adjuvant trastuzumab/pertuzumab (HER2+) or 4 or more cycles of SOC adjuvant pembrolizumab (TNBC)
* Pregnant women are not eligible to participate in this study

Where it's running

  • M D Anderson Cancer Center
    Houston, Texas, United States     Recruiting

Study contacts

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
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Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.