TroVax

There were two renal cell TroVax studies presented at ASCO, an oral presentation by Howard Kaufman of Columbia University and a poster by Robert Hawkins of The Christie Hospital, Manchester, UK.

5T4 is a protein that is over-expressed in 90% of renal cell tumors including clear cell and papillary but not in other cancer types. Simply stated, TroVax is a 5T4 vaccine that has the objective of stimulating the immune system to attack the tumor.

Columbia University Trial

In the Columbia University Phase II trial, 25 patients (21 clear cell and 4 papillary) entered the trial, to be treated with the combination of high-dose Interleukin-2 (HD IL-2) and TroVax. The maximum treatment level, if tolerated, was 8 vaccinations and 4 cycles of IL-2. All but one patient had had prior therapies.

23 patients were evaluated. There were only grade 1 adverse events to the vaccine and the normal adverse events to the IL-2. There were no partial or complete responses. 12 of the 23 (52%) had stable disease, the remaining had progressive disease. The progression-free survival was approximately 5 months. 80% of the patients were alive at 24 months, which Kaufman compared to the historical figure of 50% for IL-2 alone at Columbia University over the past five years.

Christie Hospital Trial

For the second Phase II trial, in Manchester, there were 11 patients, 10 clear cell and 1 papillary, scheduled to receive 11 immunizations with TroVax plus infusions of Interferon-alpha three times weekly. The median dosages were 9 vaccinations and 34 treatments with Interferon-alpha.

There was no sign of adverse events due to TroVax but one patient stopped treatment due to a rash from the Interferon-alpha.

The results were 10 patients with stable disease and 1 with progressive disease. The median progression-free survival was 9 months, but for clear cell patients it was 10.4 months. At median follow-up time of 15.6 months, 9 of the 11 patients were still alive.

Discussion

These were both small, Phase II studies from which it is difficult to draw conclusions. In both studies, the best response was stable disease, which is not encouraging. In the Columbia University study, the progression-free survival (PFS) was only 5 months, but the protocol used by Columbia for HD IL-2 treatment is not consistent with the standard treatment. The fact that 80% of patients were surviving at 24 months compares favorably with the Sutent figure presented at this year's ASCO. As for the Manchester study, the 10.4 months PFS is the same as the PFS of the Avastin/Interferon-alpha arm of the AVOREN trial. Median survival time has not yet been reached.

We will learn more from the Oxford BioMedica-sponsored Phase III trial called the TroVax Renal Immunotherapy Survival Trial (TRIST), now underway. TRIST has enrolled 700 patients in three arms (low dose IL-2, interferon-alpha, sunitinib (Sutent)) in a randomized (one is assigned to any arm at random), placebo-controlled (half get TroVax and half don't) testing whether TroVax affects overall survival. The Oxford BioMedica reps told ACKC that the results of the trial will be reported at next year's ASCO. This trial is no longer recruiting patients.

July 2008 Update

Oxford Biomedica announced on July 11th that, based on the fact that 190 patients out of 733 in a trial have died and trial will not meet its primary efficacy endpoint, the Drug Safety Monitoring Board has ruled that there should be no more TroVax vaccinations administered on the TRIST trial. Oxford Biomedica has agreed with this ruling and has discontinued TroVax treatment, but is continuing the trial itself, administering low dose IL-2, interferon-alpha, or sunitnib. Oxford Biomedica may continue testing TroVax in other cancer types, but this is the end of the road for TroVax in kidney cancer.