Table 2.
MVA Vaccine Trials: Renal Caner
| Vaccine Therapy (superscript number denotes reference) | Phase (No. of pts) | Immune Response to Vaccine Antigen | Clinical Outcome | |
|---|---|---|---|---|
| TROVAXa (MVA-5T4) | + IFN-α as 1st or 2nd line therapy77 | I/II (11) | 11/11 anti-5T4 antibodies, 5/11 T-cell response | No objective tumor response Median TTP 9 mo (2.1–18+ mo) |
| ± IFN-α78 | II (23) | 21/25 anti-5T4 Ab, 7/21 T-cell response Median TTP: T-cell responders, 10.2 mo; non-responders, 4.5 mo (p=0.04); Greater median OS in pts with > median fold increase in 5T4 antibodies at week 7 (p=0.01) | 1/15 PR SD: 7/15 TroVax + IFN-α; 7/13 TroVax | |
| + high dose IL-279 | I/II (25) | 23/23 anti-5T4 Ab; 13/23 increase in T-cell response | 3/25 NED post-surgery; 12/25 SD (1–18 mo) | |
| + low dose IL-280 | II (25) | 21/25 anti-5T4 Ab, 5/11 T-cell response Pts who developed greater than median anti-5T4 antibody titers had a greater TTP and better OS (p<0.05) | 2 CR (>24 mo), 1 PR (>13 mo), 6 SD (6–21 mo) Median OS >12.87 (1.9–24.76) Median TTP >3.37 (1.5–24.76) | |
| + IL-2, IFN-α, or Sunitnib vs. placebo + IL-2, IFN-α, or Sunitnib; if PD: vaccine ± sorafenib81 | III (733) | 56% developed anti-5T4 Ab More pts developed anti-5T4 Abs in MVA-5T4 + IFN-α group than in vaccine + IL-2 or vaccine + sunitinib group High 5T4 antibody responders had a favorable survival compared with placebo-treated pts |
Terminated given little prospect of showing survival benefit Pts with good prognosis receiving IL2 + vaccine vs. IL-2 alone had improved OS |
|
| TG4010 (MVA- MUC1-IL2) | Vaccine, followed by addition of IFN- α + IL-2 if PD82 | II (37) | 7/37 CD8+ T cell response; 6/28 CD4+ T-cell response MUC1-specific CD8+ T cell response associated with longer OS | Median OS 19.3 mo overall, 22.4 mo for combination therapy SD > 6 mo: 5/27 TG4010 (median SD 5.9 mo), 6/20 TG4010 + cytokines (median SD 8.4 mo) |
a
TroVax – modified vaccinia ankara (MVA) virus expressing 5T4
b
TG4010 – modified vaccinia ankara virus expressing MUC-1 and IL-2 transgenes.
TTP – time to progression; OS – overall survival; PR – partial response; NED – no evaluable disease; SD – stable disease