Clinical Data
The Phase 1/2a trial began as a dose-escalation Phase 1 trial, transitioning to a Phase 2a comparing expanded dose cohorts with a total of 51 patients enrolled, n=29 in the vaccine group (VG) and n=22 in the control group (CG). After a median follow-up of 16 months, the overall recurrence rate was 44.8% in the VG versus 54.5% in the CG (p=0.58), with a recurrence rate of only 23.5% in those patients who received booster inoculations. The estimated two-year disease free survival (DFS) is 46.3% in the VG versus 38.1% in the CG (p=0.36). Importantly, in the optimally dosed group (OPT) that received the primary vaccine series (PVS) with 1000 mcg of peptide, there was a significant survival benefit with the estimated 2-year DFS at 73.5% in the VG (n=15), versus 38.1% in the CG (n=22) (p=0.03).


Of the 51 patients, all entered the trial with no evidence of disease with 40 enrolled after completion of standard of care treatment for their primary diagnosis and 11 after completion of standard of care treatment for the recurrence of their disease. A further subset analysis was completed comparing the DFS of patients with primary or recurrent disease at enrollment. The survival benefit observed in the optimally dosed group persisted in the primary disease patients (DFS: OPT 66.7% versus CG 36.7%, p=0.02) but not in the recurrent patients (DFS: OPT 33.3% versus CG 22.2%, p=0.96).

In the Phase 1/2a trial, HLA-A2 positive patients were vaccinated and HLA-A2 negative patients were prospectively followed as a control group. The VG received six monthly inoculations of E39 + 250 mcg GM-CSF as the PVS, followed by two boosters every six months. Of the 29 vaccinated patients, 24 completed the PVS, 17 received one booster, and 14 received two boosters. There were no clinicopathologic differences between groups with primarily grade 1 and grade 2 toxicities. The three most common toxicities were injection site erythema, skin induration and pruritus, which occurred in all vaccinated patients. Immunologic evaluation was performed as a delayed type hypersensitivity (DTH) reaction pre- and post- PVS. Overall, DTH increased pre- to post-PVS in vaccinated patients (5.9+1.5 mm vs 11.7+3.2 mm, p=0.07), with a larger increase seen in the optimally dosed patients (3.8+2.0 mm vs 9.5+3.5 mm, p=0.07) versus those not optimally dosed (7.8+2.1 mm v 11+5.0 mm, p=0.24). Demographic, safety, immunologic, and recurrence data were collected and analyzed using the appropriate statistical tests.