Expanded phase I combination trial of GVAX immunotherapy for prostate cancer and ipilimumab in patients with metastatic hormone-refractory prostate cancer (mHPRC)

Abstract

5146 Background: A Phase 1 trial is underway to study GVAX immunotherapy for prostate cancer [GVAX immunotherapy (GVAX IT)] and ipilimumab (Ipi) in chemonaïve mHRPC patients (pts). Methods: Twelve pts were treated in a dose-escalation phase for 24 weeks (wks) with bi-weekly intradermal injections of GVAX IT and monthly Ipi. Pts were enrolled in cohorts of 3; each cohort received an escalating dose of Ipi: 0.3, 1, 3 or 5 mg/kg. Sixteen pts were then enrolled in an expansion cohort to be treated with GVAX IT and 3 mg/kg Ipi. Results: Escalation Cohort: Median follow-up of 12 pts is 21.2 months (m). Five of six pts at the higher Ipi doses (3 and 5 mg/kg) developed Grade 2 or 3 immune-related adverse events (irAEs), including Grade 2 or 3 hypophysitis and Grade 3 alveolitis. Late onset PSA responses (declines > 50%) were seen in these 5 pts with response durations of 6.7, 8.6, 9.5, 13.8 (on-going), and 23.1 m. Four of these pts had stable disease on bone scan for at least 12 m, and up to 21 m. Multiple tumor-reactive antibodies (abs) induced by treatment were identified by serologic analysis (SEREX), including abs to filamin B, PSMA and NY-ESO-1. Biopsies of injection sites showed T cell infiltration and Granzyme B expression; these T cells are being tested for antigen-specific lytic activity. Expansion Cohort: Sixteen pts were enrolled, 6 have completed treatment, 10 are on-going. Three pts have experienced irAEs of Grade 1 diarrhea, Grade 3 adrenal insufficiency, and a Grade 3 hepatitis that resolved with steroids. With median follow-up of 6.5 months in the 6 pts who have completed treatment, 1 pt had a PSA response (> 50% decline) and 3 obtained stable PSA, accompanied in one pt by pain relief and decrease in alkaline phosphatase. Conclusions: The GVAX IT and ipilimumab combination is active in mHRPC in this trial. IrAEs appear manageable and may correlate with anti-tumor activity. The maximum tolerated dose of the combination is not established. Follow-up on the 16 expansion cohort pts will provide data on safety, clinical activity and immunologic correlates. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Cell Genesys, Medarex Cell Genesys, Medarex Cell Genesys