A pilot study of a PANVAC-V and PANVAC-F in patients (pts) with metastatic carcinoma

Abstract

2512 Background: The vast majority of carcinomas express either MUC-1 or CEA. Preclinical and clinical studies have demonstrated that induction of T-cell responses directed against CEA and MUC-1 can lead to anti-tumor activity without toxicity. Two novel vaccines have been developed: (a) PANVAC-V (V) a recombinant vaccinia virus containing CEA and MUC-1 with modified agonist epitopes and 3 costimulatory molecule transgenes, and (b) PANVAC-F (F) a similar recombinant fowlpox virus. Methods: This pilot study enrolled 25 pts with metastatic carcinoma who had progressive disease after chemotherapy. Pts received V priming followed by F boosts every 2 weeks × 3 then monthly with restaging scans every 2 months while on study. All vaccines were given with sargramostim at the vaccine site. The primary endpoint was safety. Class I and class II immune responses to CEA were analyzed. Class I responses were assayed by ELISPOT, intracellular cytokine, and tetramer binding; and class II responses were assayed by ELISA using CEA protein and class II peptides. Results: Treatment was well tolerated with 135 cycles given. Only one grade 3 toxicity (syncope during a flu-like illness) was possibly related to vaccine. Apart from injection site reactions, only 9 cycles (7%) were associated with transient grade 2 toxicity (generally flu-like syndromes). Class I and class II immunologic responses were demonstrated. A pt with metastatic breast cancer and 5 large liver metastasis had a 24% decrease in unidimensional measurement of disease for 6 months. A pt with metastatic gastric cancer had stable disease for 5 months. Furthermore, a pt with metastatic clear cell ovarian cancer s/p chemotherapy had complete disappearance of large volume, symptomatic ascites accompanied by marked improvement in the appearance of mesenteric stranding and a CA-125 reduction from 281 U/mL to continued sustained normal values (< 20 U/mL). Conclusions: This vaccine can be given safely and can generate therapy specific immunologic responses. In addition 1 pt with metastatic ovarian cancer had a dramatic clinical response. Based on this, we have initiated a pilot study specifically for ovarian cancer pts to gain more information on which to base a large clinical endpoint trial. No significant financial relationships to disclose.