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

NCT07407920 | Active Not Recruiting Phase 2 FDA Drug FDA Device

• 3 other identifiers: 2024-1206NCI-2025-08252P30CA016672
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Early Stage HER2-Positive Breast Carcinoma; Early Stage Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Rate of conversion from negative to positive circulating tumor deoxyribonucleic acid (ctDNA)

  Up to 3 years

• Time to conversion from negative to positive ctDNA

  Up to 3 years

• Prevalence of patients with pathologic complete response (pCR) rate after receiving neoadjuvant systemic therapy (NST) and have positive ctDNA

  At 4-6 weeks after breast surgery

• EFS in patients that achieve pCR after NST and have a positive ctDNA

  From breast surgery to evidence of clinical locoregional or distant recurrence of breast cancer or death from breast cancer, up to 3 years

Study Arms (2)

Cohort 1 (Triple negative breast cancer)

EXPERIMENTAL

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; Biological: Pembrolizumab

Cohort 2 (HER2 positive breast cancer)

EXPERIMENTAL

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; Drug: Hormone Therapy; Biological: Pertuzumab; Biological: Trastuzumab

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Cohort 1 (Triple negative breast cancer); Cohort 2 (HER2 positive breast cancer)

Hormone Therapy DRUG

Given standard of care endocrine therapy

Also known as: Chemotherapy-Hormones/Steroids, Endocrine Therapy, Hormonal, Hormonal Therapy, Hormonal Treatment, hormone treatment, Hormones

Cohort 2 (HER2 positive breast cancer)

Pembrolizumab BIOLOGICAL

Given pembrolizumab

Also known as: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, Pembrolizumab Biosimilar RPH-075, Pembrolizumab Biosimilar SB27, QL2107, RPH 075, RPH-075, RPH075, SB 27, SB-27, SB27, SCH 900475, SCH-900475, SCH900475

Cohort 1 (Triple negative breast cancer)

Pertuzumab BIOLOGICAL

Given pertuzumab

Also known as: 2C4, 2C4 Antibody, BCD-178, EG1206A, HLX11, HS627, MoAb 2C4, Monoclonal Antibody 2C4, Omnitarg, Perjeta, Pertuzumab Biosimilar BCD-178, Pertuzumab Biosimilar EG1206A, Pertuzumab Biosimilar HLX11, Pertuzumab Biosimilar HS627, Pertuzumab Biosimilar TQB2440, Pertuzumab-dpzb, Poherdy, Rhumab 2C4, rhuMAb2C4, RO4368451, TQB 2440, TQB-2440, TQB2440

Cohort 2 (HER2 positive breast cancer)

Trastuzumab BIOLOGICAL

Given trastuzumab

Also known as: ABP 980, ALT02, Biceltis, CANMab, CT-P06, CT-P6, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, Hercessi, Herclon, Hertraz, Herwenda, Herzuma, HLX 02, HLX-02, HLX02, Kanjinti, Ogivri, Ontruzant, PF 05280014, PF-05280014, PF05280014, QL 1701, QL-1701, QL1701, rhuMAb HER2, RO0452317, SB3, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar ALT02, Trastuzumab Biosimilar CT-P6, trastuzumab biosimilar EG12014, Trastuzumab Biosimilar HLX02, Trastuzumab Biosimilar PF-05280014, Trastuzumab Biosimilar QL1701, Trastuzumab Biosimilar SB3, Trastuzumab Biosimilar SIBP-01, Trastuzumab-anns, Trastuzumab-dkst, Trastuzumab-dttb, Trastuzumab-herw, Trastuzumab-pkrb, Trastuzumab-qyyp, Trastuzumab-strf, Trastuzumab-zerc, Trazimera, Zercepac

Cohort 2 (HER2 positive breast cancer)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

Specimen Handling; Steroids; Hormones; pembrolizumab; pertuzumab; 2C4 antibody; Trastuzumab; CT-P6; PF-05280014; trastuzumab biosimilar HLX02; Ogivri; Ontruzant

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Fused-Ring Compounds; Polycyclic Compounds; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Vicente Valero, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2026
• First Posted: February 12, 2026
• Study Start: October 9, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

US (1)