HER2-Targeted Cancer Vaccine Shows Promise in Early Trial

October 9, 2018

A novel cancer vaccine targeting HER2-positive malignancies has progressed quickly from mouse trials into early-phase human trials, with promising results.

A novel cancer vaccine targeting HER2-positive malignancies has progressed quickly from mouse trials into early-phase human trials, with promising results. The vaccine has produced several responses and cases of stable disease, and is well tolerated.

“We are using a vaccine approach to generate an immune response to HER2, which is found at high levels on and drives the growth of several types of cancer, including breast, ovarian, lung, colorectal, and gastroesophageal cancers,” said lead author Jay A. Berzofsky, MD, PhD, of the National Cancer Institute in Bethesda, Maryland, according to a press release. He presented results of the research at the International Cancer Immunotherapy Conference, held September 30–October 3 in New York City.

The researchers developed a cancer vaccine comprised of autologous dendritic cells that are transduced with an adenovirus. The virus expresses HER2’s non-signaling extracellular transmembrane domains. They first tested this in mice, and were able to cure “virtually all” mice with large established tumors and with macroscopic lung metastases; the mechanism of action was distinct from that of the established anti-HER2 therapy trastuzumab.

Based on that success, they began a phase I trial in human patients with advanced metastatic HER2-positive cancers (including ovarian, gastroesophageal, prostate, and other malignancies); in the first part of this trial, all included patients were native to trastuzumab or any other HER2-directed therapies.

At the lowest dose of 5 million dendritic cells, no responses were seen, but at higher doses of 10 and 20 million cells, responses were observed. Of 11 evaluable patients at those dose levels, 6 patients (54%) had clinical benefit; this included one complete response lasting 89 weeks and one partial response lasting 24 weeks. Four patients had stable disease.

The vaccine was well tolerated, with injection site reactions as the most common adverse event. The patients underwent serial echocardiograms, which revealed no evidence of cardiotoxicity. Levels of circulating tumor cells also diminished in many patients; at 12 weeks, 40% of patients had a reduced number of circulating cells, while at 28 weeks this rose to 83%, and at 48 weeks 100% of the two patients remaining on study saw reduced circulating tumor cells.

Based on the results seen in this part of the trial, the researchers received approval to raise the dose to 40 million dendritic cells. They moved on to test the vaccine in patients who progressed after prior HER2-directed therapies; they primarily included patients with metastatic breast and gastric cancers.

“Moving forward, we would like to investigate whether we can increase the proportion of people who benefit from treatment with the vaccine by combining it with checkpoint inhibitor therapy,” Berzofsky said; the authors noted that the vaccine may essentially move the tumor from a “cold” state to a “hot” state, where it is more amenable to treatment with checkpoint inhibition.