Ph2 Study for Optimization of Adjunct Systemic Therapy in HER2+ Patients, MolecularPCR Trial

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)

This phase II trial tests reduced post surgery (adjuvant) therapy for patients with early breast cancer who have confirmed that the disease has responded completely (pathologic complete response) after pre surgical treatment (neoadjuvant) therapy and do not have any tumor genetic material (molecular residual disease) circulating in their blood. Standard of care treatment after surgery consists of 1 year of pembrolizumab for patients with triple negative breast cancer or trastuzumab with or without pertuzumab to complete 1 year of treatment. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pertuzumab and trastuzumab are monoclonal antibodies and forms of targeted therapy that attach to a receptor protein called HER2. HER2 is found on some cancer cells. When pertuzumab or trastuzumab attach to HER2, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Lowering the total amount of cancer therapy after breast surgery, may continue to keep the great tumor response to treatment, and may help lower the amount of side effects patients have.

Study Overview

• Status: Active, not recruiting
• Conditions: Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Early Stage Triple-Negative Breast Carcinoma; Early Stage HER2-Positive Breast Carcinoma
• Intervention / Treatment: Procedure: Biospecimen Collection; Biological: Pembrolizumab; Drug: Hormone Therapy; Biological: Pertuzumab; Biological: Trastuzumab

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the 3-year event free survival (EFS) after breast surgery in patients with early triple negative breast cancer (TNBC) that achieve a pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) with a pembrolizumab plus chemotherapy-based regimen and are minimal residual disease (MRD)-negative (negative circulating tumor deoxyribonucleic acid [ctDNA] with the NeXT Personal™ assay) at 4-6 weeks after breast surgery and discontinue standard of care (SOC) adjuvant pembrolizumab.

II. To determine the 3-year EFS after breast surgery in patients with early HER2+ breast cancer that achieve a pCR after NST with a trastuzumab and pertuzumab plus chemotherapy-based regimen and are MRD-negative (negative ctDNA with the NeXT Personal™ assay) at 4-6 weeks after breast surgery and discontinue SOC adjuvant trastuzumab and pertuzumab.

SECONDARY OBJECTIVES:

I. To estimate the rate of conversion from negative to positive ctDNA and time to conversion from negative to positive ctDNA among patients who undergo de-escalation of SOC adjuvant systemic therapy.

II. To establish the prevalence of patients with early TNBC or early HER2+ breast cancer who achieve a pCR after receiving NST and have a positive ctDNA with the NeXT Personal™ assay at 4-6 weeks after breast surgery.

III. To determine the 3-year EFS after breast surgery in patients with early HER2+ breast cancer or early TNBC that achieve a pCR after NST and have a positive ctDNA with the NeXT Personal™ assay at 4-6 weeks after breast surgery.

OUTLINE: Patients with triple negative breast cancer are assigned to cohort 1, patients with HER2 positive breast cancer are assigned to cohort 2.

COHORT 1: Patients may receive 1 to 3 cycles of standard of care treatment with pembrolizumab. Patients with a positive ctDNA test 4-6 weeks after surgery continue to receive standard of care treatment per their treating physician in the absence of disease progression or unacceptable toxicity. Patients with a negative ctDNA test will not receive further treatment with pembrolizumab and will undergo monitoring with ctDNA tests every 3 months for 3 years in the absence of disease progression.

COHORT 2: Patients may receive 1 to 3 cycles of standard of care treatment with trastuzumab with or without pertuzumab. Patients with a positive ctDNA test 4-6 weeks after surgery continue to receive standard of care treatment per their treating physician in the absence of disease progression or unacceptable toxicity. Patients with a negative ctDNA test will not receive further treatment with pembrolizumab and will undergo monitoring with ctDNA tests every 3 months for 3 years in the absence of disease progression. Patients may receive standard of care endocrine therapy per their treating physician throughout the study.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (Triple negative breast cancer); Patients may receive 1 to 3 cycles of standard of care treatment with pembrolizumab. Patients with a positive ctDNA test 4-6 weeks after surgery continue to receive standard of care treatment per their treating physician in the absence of disease progression or unacceptable toxicity. Patients with a negative ctDNA test will not receive further treatment with pembrolizumab and will undergo monitoring with ctDNA tests every 3 months for 3 years in the absence of disease progression. Patients undergo blood sample collection throughout the study.	Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Biological: Pembrolizumab; Given pembrolizumab; Other Names: Keytruda; MK-3475; Lambrolizumab; SCH 900475; MK3475; SCH-900475; BCD-201; Pembrolizumab Biosimilar BCD-201; Pembrolizumab Biosimilar QL2107; QL2107; GME 751; GME751; Pembrolizumab Biosimilar GME751; MK 3475; SCH900475; Pembrolizumab Biosimilar RPH-075; RPH 075; RPH-075; RPH075; Pembrolizumab Biosimilar SB27; SB 27; SB-27; SB27
Experimental: Cohort 2 (HER2 positive breast cancer); Patients may receive 1 to 3 cycles of standard of care treatment with trastuzumab with or without pertuzumab. Patients with a positive ctDNA test 4-6 weeks after surgery continue to receive standard of care treatment per their treating physician in the absence of disease progression or unacceptable toxicity. Patients with a negative ctDNA test will not receive further treatment with pembrolizumab and will undergo monitoring with ctDNA tests every 3 months for 3 years in the absence of disease progression. Patients may receive standard of care endocrine therapy per their treating physician throughout the study. Patients undergo blood sample collection throughout the study.	Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Hormone Therapy; Given standard of care endocrine therapy; Other Names: Chemotherapy-Hormones/Steroids; Endocrine Therapy; Hormonal Therapy; hormone treatment; Hormones; Hormonal; Hormonal Treatment; Biological: Pertuzumab; Given pertuzumab; Other Names: Perjeta; 2C4; 2C4 Antibody; EG1206A; HLX11; HS627; MoAb 2C4; Monoclonal Antibody 2C4; Omnitarg; Pertuzumab Biosimilar EG1206A; Pertuzumab Biosimilar HLX11; Pertuzumab Biosimilar HS627; rhuMAb2C4; RO4368451; BCD-178; Pertuzumab Biosimilar BCD-178; Rhumab 2C4; Pertuzumab Biosimilar TQB2440; TQB 2440; TQB-2440; TQB2440; Pertuzumab-dpzb; Poherdy; Biological: Trastuzumab; Given trastuzumab; Other Names: Herceptin; ABP 980; ALT02; Herceptin Biosimilar PF-05280014; Herceptin Trastuzumab Biosimilar PF-05280014; Herzuma; Ogivri; Ontruzant; PF-05280014; rhuMAb HER2; RO0452317; SB3; Trastuzumab Biosimilar ABP 980; Trastuzumab Biosimilar ALT02; trastuzumab biosimilar EG12014; Trastuzumab Biosimilar HLX02; Trastuzumab Biosimilar PF-05280014; Trastuzumab Biosimilar SB3; Trastuzumab-dkst; Trastuzumab-dttb; Trastuzumab-pkrb; Trazimera; Kanjinti; Trastuzumab Biosimilar SIBP-01; Trastuzumab-anns; Trastuzumab-qyyp; Herclon; Zercepac; QL 1701; QL-1701; QL1701; Trastuzumab Biosimilar QL1701; CT-P06; CT-P6; Trastuzumab Biosimilar CT-P6; Biceltis; CANMab; Hertraz; Hercessi; Trastuzumab-strf; Herwenda; Trastuzumab-herw; Trastuzumab-zerc; HLX 02; HLX-02; HLX02; PF 05280014; PF05280014

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event free survival (EFS)	Will be independently estimated for each cohort, along with corresponding 95% confidence intervals using Kaplan-Meier method.	From breast surgery to evidence of clinical locoregional or distant recurrence of breast cancer or death from breast cancer, up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of conversion from negative to positive circulating tumor deoxyribonucleic acid (ctDNA)	95% confidence interval will be calculated by cohort using the Clopper-Pearson method.	Up to 3 years
Time to conversion from negative to positive ctDNA	Will be estimated using the Kaplan-Meier method.	Up to 3 years
Prevalence of patients with pathologic complete response (pCR) rate after receiving neoadjuvant systemic therapy (NST) and have positive ctDNA	The 95% confidence intervals for the prevalence estimates will be calculated using Clopper-Pearson method.	At 4-6 weeks after breast surgery
EFS in patients that achieve pCR after NST and have a positive ctDNA	EFS at 3 years with their 95% confidence intervals will be estimated using Kaplan-Meier method. Log-rank test will be performed to test the difference in time-to-event distributions between patient groups.	From breast surgery to evidence of clinical locoregional or distant recurrence of breast cancer or death from breast cancer, up to 3 years

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: VIcente Valero, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: February 6, 2026
• First Submitted That Met QC Criteria: February 6, 2026
• First Posted (Actual): February 12, 2026

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Peptides, and Proteins; Proteins; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Pharmacologic Actions; Chemical Actions and Uses; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Fused-Ring Compounds; Trastuzumab; Hormones; Specimen Handling; pertuzumab; pembrolizumab; Steroids; 2C4 antibody; CT-P6; PF-05280014; trastuzumab biosimilar HLX02; Ogivri; Ontruzant
• Other Study ID Numbers: 2024-1206 (Other Identifier: M D Anderson Cancer Center); P30CA016672 (U.S. NIH Grant/Contract); NCI-2025-08252 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No