Neoadjuvant Intratumoral Dendritic Cell Vaccine Therapy Plus Paclitaxel, Trastuzumab, and Pertuzumab in HER2-Positive BC

Preclinical evidence indicates strong anti-HER2 immune responses and antitumor activity with intratumoral (IT) dendritic cell (DC1) vaccine therapy in combination with immunoglobulin G1 (IgG1)-mediated antibody-dependent cellular cytotoxicity. Based on such evidence, a phase 1/2 study (NATASHA trial; NCT05325632) was conducted to evaluate the efficacy and immune responses of neoadjuvant IT DC1 vaccine therapy plus trastuzumab and pertuzumab (TP, as source of IgG1) followed by 12 weeks of paclitaxel and TP. The safety and immune correlates of this study were reported at the 2023 annual ASCO meeting.

Patients with early-stage HER2-positive breast cancer with tumor size ≥1 cm were included in the study. Eligible patients received IT DC1 (weekly for 6 weeks) followed by paclitaxel (80 mg/m2 intravenously [IV] weekly for 12 weeks), trastuzumab IV every 3 weeks (8 mg/kg loading dose, then 6 mg/m2), and pertuzumab (IV every 3 weeks; 840 mg loading dose, then 420 mg) for 6 cycles starting from day 1. In phase 1, 2 dose levels of IT DC1 (50 million and 100 million cells) were evaluated at week 6 (n=6 in each dose level). An additional 22 patients will be enrolled in the expansion phase 2 trial after the optimal dose level is established. The primary end points of the phase 1 study are safety and immune responses. Date of data cutoff was February 1, 2023.

A total of 12 eligible patients were enrolled in the study, with a median age of 57; 9 patients had hormone receptor (HR)–positive disease, and 4 patients had node-positive disease. Overall, radiologic responses included 8 partial responses,3 complete responses, and 1 stable disease. Complete responses were achieved by all 3 patients with HR-negative/low disease. Subsequently, 11 patients underwent surgery, and 7 of these patients achieved pathological complete response. Common adverse events (all grades) included chills (50%), diarrhea (42%), nausea (42%), and fatigue (42%) during the first 6 weeks of IT DC1/TP; and diarrhea (67%), peripheral neuropathy (67%), fatigue (58%), and rash (58%) during the paclitaxel/TP phase. In terms of immune response, IT DC1 vaccine injections at a dose of 100 million cells resulted in a significant decrease of HER2-specific T-cell response.

The authors concluded that the addition of IT DC followed by TP to neoadjuvant chemotherapy was well tolerated with manageable toxicities.


Han HS, Costa RL, Armghani AJ, et al. 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. Abstract presented at: ASCO Annual Meeting, June 2-6, 2023; Chicago, IL. Abstract 596.

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