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Phase I Clinical Trial of an Autologous Dendritic Cell Vaccine Against HER2 Shows Safety and Preliminary Clinical
Hoyoung M Maeng1, Brittni N Moore1, Hadi Bagheri2
1Vaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States.
Background:
Despite recent advances, there is an urgent need for agents targeting HER2-expressing cancers other than breast cancer. We report a phase I study (NCT01730118) of a dendritic cell (DC) vaccine targeting HER2 in patients with metastatic cancer or bladder cancer at high risk of relapse.
Patients And Methods:
Part 1 of the study enrolled patients with HER2-expressing metastatic cancer that had progressed after at least standard treatment and patients who underwent definitive treatment for invasive bladder cancer with no evidence of disease at the time of enrollment. Part 2 enrolled patients with HER2-expressing metastatic cancer who had progressed after anti-HER2 therapy. The DC vaccines were prepared from autologous monocytes and transduced with an adenoviral vector expressing the extracellular and transmembrane domains of HER2 (AdHER2). A total of five doses were planned, and adverse events were recorded in patients who received at least one dose. Objective response was evaluated by unidimensional immune-related response criteria every 8 weeks in patients who received at least two doses. Humoral and cellular immunogenicity were assessed in patients who received more than three doses.
Results:
A total of 33 patients were enrolled at four dose levels (5 × 106, 10 × 106, 20 × 106, and 40 × 106 DCs). Median follow-up duration was 36 weeks (4-124); 10 patients completed five doses. The main reason for going off-study was disease progression. The main adverse events attributable to the vaccine were injection-site reactions. No cardiac toxicity was noted. Seven of 21 evaluable patients (33.3%) demonstrated clinical benefit (1 complete response, 1 partial response, and 5 stable disease). After ≥3 doses, an antibody response was detected in 3 of 13 patients (23.1%), including patients with complete and partial responses. Lymphocytes from 10 of 11 patients (90.9%) showed induction of anti-HER2 responses measured by the production of at least one of interferon-gamma, granzyme B, or tumor necrosis factor-alpha, and there were multifunctional responses in 8 of 11 patients (72.7%).
Conclusions:
The AdHER2 DC vaccine showed evidence of immunogenicity and preliminary clinical benefit in patients with HER2-expressing cancers, along with an excellent safety profile. It shows promise for further clinical applications, especially in combination regimens.
Insights
This study shows a new dendritic cell (DC) vaccine targeting HER2-expressing cancers is safe and effective. The AdHER2 DC vaccine demonstrated immunogenicity and clinical benefit in patients with metastatic or bladder cancer.
Area of Science:
- Oncology
- Immunotherapy
- Vaccine Development
Background:
- Urgent need for novel therapeutic agents targeting HER2-expressing cancers beyond breast cancer.
- HER2 is a validated target in several cancer types, including metastatic and bladder cancers.
- Existing treatments for HER2-expressing cancers have limitations, necessitating alternative strategies.
Purpose of the Study:
- To evaluate the safety and immunogenicity of a novel dendritic cell (DC) vaccine targeting HER2 (AdHER2 DC vaccine).
- To assess the preliminary clinical activity of the AdHER2 DC vaccine in patients with HER2-expressing metastatic or bladder cancer.
- To determine the optimal dose and tolerability of the AdHER2 DC vaccine in a Phase I clinical trial.
Main Methods:
- Phase I clinical trial (NCT01730118) involving patients with HER2-expressing metastatic cancer or high-risk bladder cancer.
- Autologous dendritic cells (DCs) were transduced with an adenoviral vector expressing HER2 (AdHER2).
- Patients received up to five doses of the AdHER2 DC vaccine at escalating dose levels; safety, immunogenicity, and objective response were assessed.
Main Results:
- 33 patients were enrolled across four dose levels; median follow-up was 36 weeks.
- The AdHER2 DC vaccine was well-tolerated, with injection-site reactions as the primary adverse events; no cardiac toxicity was observed.
- Clinical benefit was observed in 33.3% of evaluable patients (1 complete response, 1 partial response, 5 stable disease); significant cellular anti-HER2 immune responses were induced in 90.9% of patients.
Conclusions:
- The AdHER2 DC vaccine demonstrated promising immunogenicity and preliminary clinical benefit in patients with HER2-expressing cancers.
- The vaccine exhibited an excellent safety profile, supporting its potential for further clinical development.
- The AdHER2 DC vaccine shows potential for future applications, particularly in combination therapeutic regimens.
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