Preclinical evidence indicates strong anti-HER2 immune responses and antitumor activity with intratumoral dendritic cell vaccine therapy in combination with immunoglobulin G1 (IgG1)-mediated antibody-dependent cellular cytotoxicity. Based on such evidence, the phase 1/2 NATASHA study was conducted to evaluate the efficacy of and immune responses to neoadjuvant intratumoral dendritic cell vaccine therapy plus trastuzumab and pertuzumab (as a source of IgG1) followed by 12 weeks of treatment with paclitaxel plus trastuzumab and pertuzumab. 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 a tumor size of ≥1 cm were included in the study. Eligible patients received intratumoral dendritic cell vaccine therapy weekly for 6 weeks followed by intravenous (IV) paclitaxel 80 mg/m2 weekly for 12 weeks, IV trastuzumab every 3 weeks (8-mg/kg loading dose, then 6 mg/m2), and IV pertuzumab (every 3 weeks; 840-mg loading dose, then 420 mg) for 6 cycles starting from day 1. In phase 1, 2 dose levels of intratumoral dendritic cell (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 phase 2 expansion trial after the optimal dose level is established. The primary end points of the phase 1 study are safety and immune responses. The data cutoff date was February 1, 2023.
A total of 12 eligible patients were enrolled in the study, with a median age of 57 years; 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 patient with stable disease. Complete responses were achieved by all 3 patients with HR-negative or HR-low disease. Subsequently, 11 patients underwent surgery, and 7 of these patients achieved a pathologic complete response. The common adverse events (all grades) included chills (50%), diarrhea (42%), nausea (42%), and fatigue (42%) during the first 6 weeks of intratumoral dendritic cell/TP; and diarrhea (67%), peripheral neuropathy (67%), fatigue (58%), and rash (58%) during the paclitaxel plus trastuzumab and pertuzumab treatment phase. In terms of immune response, intratumoral dendritic cell vaccine injections at a dose of 100 million cells resulted in a significant decrease of HER2-specific T-cell response.
The investigators concluded that the addition of intratumoral dendritic cell therapy followed by trastuzumab and pertuzumab to neoadjuvant chemotherapy was well tolerated with manageable adverse events.
Source: 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.