Of the three patients given the highest dose of the vaccine, two have exhibited stable disease for 6 months and the third patient has maintained stable disease for 9 months, said Alexandra Drakaki, MD, PhD, assistant professor of hematology/oncology and urology at the University of California at Los Angeles.
In her oral presentation, Drakaki said the vaccine is directed at the ubiquitous membranous expression of carbonic anhydrase IX (CAIX) in renal cell carcinoma. After 10 years of experimentation, the research team developed a fusion gene construct, granulocyte-macrophage colony-stimulating factor plus CAIX, transduced by a replication deficient adenovirus into autologous dendritic cells that are injected in patients with metastatic renal cell carcinoma who express CAIX.
In the process, patients undergo leukapheresis, and peripheral mononeuclear cells are harvested. Dendritic cells are then transduced with AD-GM-CAIX. On day 7 after leukapheresis, the cells are infused back into the patients with metastatic renal cell carcinoma.
The phase I study was designed to determine if infusing the cells into the patients was safe. The cells were infused in a classic 3-by-3 dose escalation. The lowest dose was 2 x 106 given every 2 weeks for 3 doses. The next level dose was 10 x 106 followed by the highest dose of 50 x 106.
Patients who were eligible for the treatment had to have histologically-documented renal clear cell carcinoma with measurable disease who had also received one or two previous treatments for metastatic kidney cancer. They had to be in ECOG performance status 0 or 1. The patients were required to have normal renal, liver, and bone marrow function.
The trialists ruled ineligible patients with rapidly progressing disease who had less than 3 months of life expectancy; had systemic infections; had received immunotherapy within 30 days, and had untreated central nervous system metastases.
Patients underwent a 28-day screening before leukapheresis. Then came the 7-to-9 day preparation of the engineered cells. Then came the first injection, 14 days later the second injection, and then the third dose another 14 days later. About 28 days after that, tumor imaging was performed. Immune monitoring was performed at baseline and then after each infusion, and after the first scan and again 6 months later.
So far, Drakaki and colleagues have screened 15 patients for the study, and nine patients were enrolled; all nine received all 3 doses. Six of the patients are in their 60s; two were in their 50s, and one patient was in their 70s. Six of the patients were white; two were Asian and one was Latin American.
There were no serious adverse events, Drakaki said. Grade 1 fatigue was experienced by three patients; one patient experienced Grade 1 joint pain; one patient experienced Grade 1 fever. Grade 2 back pain, headache, and fatigue were experienced by one patient each.
One of the secondary endpoints, monitoring immune response to GM-CAIX in dendritic cells of responders, was positive, Drakaki reported.
“CAIX is a potential target for clear cell carcinoma,” she said. “Dendritic cell-CAIX vaccination at the highest dose is feasible, safe, and triggers a CAIX specific immune response. CAIX vaccine monotherapy in the highest dose is associated with stable disease.”
Drakaki said the next step in the project is to complete the immunological endpoints and assays, and then complete the ongoing phase I monotherapy study, including treating the expansion cohort with the highest dose. After that, the researchers are posing combination therapy with checkpoint inhibitors or tyrosine kinase inhibitors, she said.
by Ed Susman, Contributing Writer, MedPage TodayNovember 06, 2017
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