Abstract #724: A phase 1 clinical trial of immune response and safety of an active immunotherapy regimen co-targeting PRAME and PSMA antigens in subjects with advanced solid malignancies
Authors: Mihail Obrocea, Nicholas Vogelzang, Lee Cranmer, Marc Ernstoff, Jeffrey Weber, John Marshall, Zhiong Qiu, Darlene Rosario, Adrian Bot
Journal: Cancer Research (2009)

Background:This clinical trial is testing an investigational immunotherapeutic 3-component regimen encompassing a recombinant plasmid (pPRA-PSM) dose followed by 2 peptide (E-PSM and E-PRA) doses (low and high) delivered by intra lymph node injection in a prime-boost sequence aimed to elicit an immune response against PRAME and PSMA antigens. Methods: The trial design used a prime-boost strategy with all patients receiving a fixed priming dose (2,400 µg/dose) of the plasmid-antigen vector via ultrasound guided intranodal injection into inguinal or axillary lymph nodes on days 1, 4, 15 and 18 of each treatment cycle followed by peptide administrations on days 29 and 32. The peptide doses used are as follows: low dose cohort: E-PSM: 30 \#956;g/dose, E-PRA: 22.5\#956;g/dose; high dose cohort: E-PSM: 300\#956;g/dose, E-PRA: 150\#956;g/dose. All patients enrolled have advanced and/or refractory carcinomas, are HLA*0201+ and tumor samples obtained from prior biopsies show presence of both PRAME and PSMA antigens. Immunologic evaluation occurs prior to treatment and on days 29 and 39 of each cycle with clinical evaluation for disease status every 2nd cycle. Patients that do not exhibit disease progression as defined by the protocol remain on study and may receive up to 6 cycles of treatment. Immune response as measured by flow cytometry using PBMCs quantifies the frequency of CD8+ tetramer+ T cells specific for PRAME and PSMA epitopes. In addition, a second immune response measurement, a direct ELISPOT analysis is used to determine the frequency of IFN gamma producing spot forming colonies. Results:Preliminary immune and clinical responses are available from 12 patients (6 melanoma, 4 prostate, 1 renal, 1 esophageal cancer and 1 mesothelioma) treated in the low peptide dose cohort. Ten patients completed 2 or more cycles of therapy. Positive immune responses (tetramer assay) against at least one immunizing antigen were noted in at least 6 patients with 3 patients showing sustained immune responses beyond 2 cycles of treatment. Most frequent treatment related adverse events reported were: fatigue, pain at injection site and chills (all grade 1 or 2). Clinical benefit was observed in 3 patients: 1 patient (ocular metastatic melanoma) completed 6 cycles with stable disease (SD), 1 patient (metastatic kidney cancer) had SD by end of cycle 4 and 1 patient (metastatic prostate cancer) had a decrease in the PSA > 60%. In the high dose peptide cohort, 10 patients received treatment with 6 patients on-going. Conclusions: To date treatment has been well-tolerated and positive immune responses were observed. A full clinical data set and any observed correlation(s) between immune responses and clinical outcome will be presented.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 724.