Neoadjuvant therapy of HER2 directed conventional dendritic cell (DC1) intratumoral (IT) therapy plus weekly paclitaxel, trastuzumab, and pertuzumab in patients with HER-2 positive breast cancer: NATASHA trial.

person Hyo S. Han H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL info_outline Hyo S. Han, Ricardo L Costa, Avan J. Armaghani, Susan Hoover, John Kiluk, Marie Catherine Lee, Hatem Hussein Soliman, Hung T. Khong, Loretta S. Loftus, Qianxing Mo, Jennifer A Childress, Edith Abraham, Kaitlin Hendrix, Amy Aldrich, Marina Sehovic, Zena Jameel, Shannon Falcon, Robert J Weinfurtner, Aixa Elena Soyano Muller, Brian J. Czerniecki

Authors person Hyo S. Han H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL info_outline Hyo S. Han, Ricardo L Costa, Avan J. Armaghani, Susan Hoover, John Kiluk, Marie Catherine Lee, Hatem Hussein Soliman, Hung T. Khong, Loretta S. Loftus, Qianxing Mo, Jennifer A Childress, Edith Abraham, Kaitlin Hendrix, Amy Aldrich, Marina Sehovic, Zena Jameel, Shannon Falcon, Robert J Weinfurtner, Aixa Elena Soyano Muller, Brian J. Czerniecki Organizations H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, H. Lee Moffitt Cancer Center, Tampa, FL, H. Lee Moffit Cancer Center, Tampa, FL Abstract Disclosures Research Funding Institutional Funding Mofffitt Cancer Center Breast Research Funding Background: Early stage HER2 positive breast cancer (BC) patients (pts) are commonly treated with neoadjuvant HER2-targeted therapy. Optimizing neoadjuvant therapy by improving efficacy while reducing toxicity is a critical unmet need. IT DC 1 therapy combined with an IgG1 antibody mediating ADCC drives strong anti-HER-2 CD4 Th1 responses and complete tumor regression in preclinical models. We initiated a phase I/II neoadjuvant study to explore the efficacy and immune stimulation effects of an initial 6 weeks of immunotherapy phase (IP) using IT DC1 vaccine plus trastuzumab (H) and pertuzumab (P) (as source of IgG1) followed by 12 weeks of paclitaxel (T) and HP. Methods: Early stage HER2+ BC pts with tumor ≥ 1cm were eligible. Treatment included IT DC1 weekly x6 followed by paclitaxel 80 mg/m 2 IV weekly x 12. Trastuzumab IV every (q) 3 weeks (8 mg/kg loading dose, then 6 mg/m 2 ) and pertuzumab IV q 3 weeks (840 mg loading dose, then 420 mg) x 6 cycles starting from day 1. Two dose levels (DL) of IT DC1 (DL1 = 50 million and DL2 = 100 million cells) were evaluated including 6 pts in each DL. Once the optimal DL is determined based on toxicities, additional 22 patients will be enrolled in expansion phase 2 trial. The primary end point of the phase 1 is the safety, immune responses (measured by ELISPOT). MRI breast was performed at the baseline, post-immunotherapy and post-chemotherapy. Here we are reporting the safety and immune correlates in phase 1 study. Results: Twelve pts were enrolled between 10/2021 and 10/2022. Median age was 57 (range 34-74). Nine pts had hormone receptor positive disease with clinical stage I/II/III (5/5/2) and 4 pts had node positive disease. All pts completed IP and 10 patients completed THP chemotherapy as of 2/1/2023. Radiologic response per MRI breast on pre and post-IP showed 6 partial response, 3 complete response and 3 stable disease. Nine pts underwent surgery and 6 out of 9 pts had pCR (RCB 0). The most frequently observed toxicities were chills (50%), diarrhea (42%), nausea (42%), fatigue (42%), and headache (42%). ELISPOT demonstrated a significant decrease of HER2- specific T cell response following 6 weeks of DC1 IT injections in DL2 compared to DL1. Conclusions: The addition of IT DC1/HP to neoadjuvant chemotherapy was well tolerated with manageable toxicities. The 100 million DC1 led to a significant decrease in peripherally circulating anti-HER2 T cell response at week 6 following IP and improved radiologic tumor responses which correlates with a higher likelihood of pCR. Data from another IT DC1 trial suggests decreased circulating HER2 responsive T cells are due to increased trafficking of reactive T cells out of circulation into the tumor possibly leading to an enhanced anti-tumor effect. Updated results including correlative biomarkers will be presented at the meeting. Clinical trial information: NCT05325632.

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