The MolecularPCR Trial is a Phase II interventional study at MD Anderson Cancer Center investigating whether adjuvant therapy intensity can be safely reduced in patients with early HER2-positive breast cancer or TNBC who achieved pathologic complete response after neoadjuvant therapy and test negative for circulating molecular residual disease. The trial is currently recruiting.
MD Anderson Cancer Center has initiated the MolecularPCR Trial (NCT07407920), a Phase II interventional study examining adjuvant therapy de-escalation in patients with early-stage HER2-positive breast cancer or triple-negative breast cancer (TNBC) who demonstrate both pathologic complete response (pCR) following neoadjuvant systemic therapy and absence of circulating molecular residual disease (MRD-negative status) at the time of surgery.
Current standard-of-care adjuvant regimens for these populations include up to one year of pembrolizumab for TNBC and trastuzumab with or without pertuzumab to complete one year of HER2-directed therapy. The trial's central hypothesis is that patients who have achieved pCR and are confirmed MRD-negative by liquid biopsy represent a biologically favorable subgroup in whom full-duration adjuvant exposure may be reducible without compromising oncologic outcomes, while potentially lowering cumulative toxicity burden.
The mechanistic rationale draws on the distinct roles of the agents under study: pembrolizumab functions as a PD-1 checkpoint inhibitor augmenting immune-mediated tumor surveillance, while trastuzumab and pertuzumab are HER2-targeted monoclonal antibodies that block receptor-driven proliferative signaling and facilitate antibody-dependent cellular cytotoxicity. Eligible participants span AJCC v8 anatomic Stage I–II disease. Biospecimen collection is incorporated to support MRD assessment and correlative analyses. The trial is currently recruiting.
Key points
- Phase II trial testing adjuvant therapy de-escalation in pCR-achieving, MRD-negative early HER2+ breast cancer and TNBC
- MRD-negative status confirmed via circulating tumor DNA liquid biopsy is a key eligibility criterion
- Adjuvant regimens under evaluation include pembrolizumab (TNBC) and trastuzumab ± pertuzumab (HER2+)
- Primary rationale: preserve oncologic efficacy while reducing cumulative toxicity in a biologically favorable subgroup
- Recruiting at MD Anderson Cancer Center; AJCC v8 Stage I–II eligible
Why it matters
Identifying patients with early HER2+ breast cancer or TNBC who can safely receive less adjuvant therapy without compromising disease control addresses a critical gap in precision oncology, potentially sparing low-risk patients from unnecessary immunotherapy- and HER2-directed therapy-related toxicities. Integration of ctDNA-based MRD assessment as a biomarker-driven eligibility criterion represents an evolving paradigm in adjuvant treatment personalization.