Trial of Retifanlimab With Trastuzumab and Pertuzumab Combination in HER2-Addicted Breast Cancer

This is a Phase II study evaluating the efficacy of retifanlimab, trastuzumab and pertuzumab (RTP) in HER2- addicted breast cancer. Male and female patients, aged ≥18 years, with HER2-addicted breast cancer (low relapse score on HER2Dx assay or PDL \>10%) will be eligible to participate in the trial. At least 30 cancer patients will be enrolled in the trial. Based on previous experience, approximately 75% of patients who had a low HER2Dx® survival score or had a PDL1-CPS score \>10% achieved a pathologic complete response (pCR) after neoadjuvant combination treatment with immunotherapy and HER2-directed antibodies (NCT03820141). Therefore, in the current trial, patients who meet this criteria will receive 6 cycles of retifanlimab, trastuzumab and pertuzumab (21-days cycles). Patients will undergo breast MRI and physical exam after completion of 6 cycles of RTP therapy. Patients who have a radiologic and clinical complete response will have surgery and will then receive the adjuvant RTP for 11 cycles. Patients who have not had a complete clinical and radiographic response will have a biopsy to prove pathologic residual disease. These patients will then receive standard-of-care (SOC) neoadjuvant chemotherapy per treating physician's discretion. Patients who are estrogen receptor (ER) positive and HER2+ will also receive aromatase inhibitor (+/- ovarian suppression, depending on menopausal status) with the RTP study treatment. Correlative studies will include tissue and blood-based molecular and genetic biomarkers of response and resistance to the regimen. Study follow-ups will be provided every 12 weeks, as per standard-of-care. The primary endpoint of the trial will be pathologic response rate (RCB- 0) in the breast and lymph nodes after 6 cycles of retifanlimab, trastuzumab and pertuzumab in patients with HER2- addicted breast cancer. We hypothesize that retifanlimab, trastuzumab and pertuzumab in patients with HER2-addicted breast cancer will have a pathologic complete response rate of 75%.