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• W2912404450 abstract "We developed and tested in mice and human patients a therapeutic cancer vaccine targeting HER2-expressing cancers comprising autologous dendritic cells (DCs) transduced with an adenovirus expressing the non-signaling extracellular and transmembrane domains of HER2, a driver oncogene in many cancers including breast, ovarian, lung, colorectal, gastroesophageal, and bladder, and others. In mice, the homologous vaccine cured virtually all mice with large established tumors up to 2 cm and with established macroscopic lung metastases, and the protection was dependent on antibodies to HER2 that inhibited HER2 phosphorylation, but was FcR (ADCC) independent, and thus distinct from the main recognized mechanism of the clinically-approved anti-HER2 monoclonal antibody, trastuzumab. We are carrying out a phase I clinical trial in patients with advanced metastatic cancers who had progressed on treatment with at least one line of standard therapy, with tumors that are HER2 1+, 2+ or 3+ by immunohistochemistry or have a HER2 FISH score ≥ 1.8. Part 1 of the trial was carried out in patients naive to trastuzumab or other HER2-directed therapies, to be able to demonstrate safety in the absence of complicating effects of prior HER2-targeted therapies. In Part 1, although no responses were seen in 6 patients at the lowest dose of 5 million DCs, at the second and third dose escalations (10 and 20 million DCs), of 11 evaluable patients, 6 (54%) had clinical benefit, including one complete response (CR) lasting 89 weeks, one partial response (PR) lasting 24 weeks, and 4 cases of stable disease (SD), seen in patients with metastatic ovarian, gastroesophageal, prostate or colorectal cancers. Adverse reactions were mainly injection site reactions that generally did not require treatment. Serial echocardiograms did not reveal any evidence of cardiotoxicity. The number of circulating tumor cells also decreased in 40% (8/20), 83% (5/6) and 100% (2/2) at 12, 28 and 48 weeks on study, respectively. Based on these results and safety data, the FDA and IRB approved increasing the maximum dose to 40 million DCs and opening Part 2 of the trial in patients who have progressed after prior HER2-directed therapies such as trastuzumab, mostly metastatic breast and gastric cancer patients. Early results in Part II already showed 2 patients with SD. Thus, we have translated a cancer vaccine from mice to human clinical trials with very promising early results, and intend to combine this vaccine with checkpoint inhibitors, as vaccines can induce T-cell responses that turn “cold” tumors into “hot” ones amenable to checkpoint blockade immunotherapy. Citation Format: Jay A. Berzofsky, Lauren V. Wood, Hoyoung Maeng, Jane Trepel, David Stroncek, John C. Morris. HER2 cancer vaccine phase I clinical trial shows clinical benefit in 54% of evaluable patients [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A004." @default.
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• W2912404450 date "2019-02-01" @default.
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• W2912404450 title "Abstract A004: HER2 cancer vaccine phase I clinical trial shows clinical benefit in 54% of evaluable patients" @default.
• W2912404450 doi "https://doi.org/10.1158/2326-6074.cricimteatiaacr18-a004" @default.
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