TroVax

Indication

All solid tumors where the 5T4 tumor antigen is present. Clinical development is ongoing in renal cell carcinoma, colorectal cancer, lung cancer, and prostate cancer, and is planned in breast cancer.

Technical design

TroVax is a proprietary tumor-associated antigen, 5T4, delivered by the pox virus vector, modified vaccinia virus Ankara (MVA).

Clinical status

Over 150 patients have been treated with collectively over 500 doses of TroVax in clinical trials. TroVax has been safe and tolerable, with no serious adverse effects. TroVax has induced an anti-tumor immune response to the 5T4 tumor antigen in over 95% of evaluable patients. The strongest immune responders have also tended to show the greatest clinical benefit.

Oxford BioMedica began patient recruitment in a Phase III trial in renal cell carcinoma in November 2006. The trial was halted in August 2008 as it was assessed that it would not meet its endpoint. Subsequent analysis has shown that Trovax was not effective on patients with poor blood chemistry (approx 50% of the patients) but that if patients were screened for blood chemistry it may have met its end point. Further phase II trials in different indications are ongoing to prove this proposition.

Colorectal cancer

TroVax was administered as a single agent post chemotherapy to combat Stage IV colorectal cancer. It induced an anti-tumor immune response in 94% of patients while 41% of patients showed periods of disease stabilization. The immune response induced by TroVax correlated with time to disease progression (p < 0.01) and a relationship was determined with survival

Colorectal cancer (two trials)

TroVax was administered alongside first-line chemotherapy to combat Stage IV colorectal cancer. It induced an anti-tumor immune response in all patients while 95% of patients showed disease stabilization and 17% of patients showed complete tumor responses. In the TroVax plus FOLFOX trial, the immune response induced by TroVax correlated with tumour responses (p < 0.02). 25% of patients were alive at an average follow-up time of almost two and a half years.

Colorectal cancer

TroVax is administered as an adjuvant to surgery to combat Stage IV colorectal cancer with operable liver metastases. It induced an anti-tumor immune response in 95% of patients while 56% of patients remained disease-free at a median follow-up of nine months.

Renal cell carcinoma (four trials)

Trovax is administered alongside interleukin-2 or interferon-alpha to combat advanced or metastatic renal cell carcinoma. It has induced an anti-tumor immune response in 88% of patients while several patients have shown partial tumor responses.

Prostate cancer

Trovax is administered either as a single agent or in combinations with GM-CSF to combat hormone-refractory prostate cancer. It has mounted an immune response in 85% of patients. Further data will be announced in November 2006.

Renal cell carcinoma

Trovax is administered in combinations with interleukin-2, interferon-alpha, sunitinib to combat advanced or metastatic renal cell carcinoma to 700 patients, with the primary endpoint being the rate of overall survival. There is a Special Protocol Assessment agreement with the FDA that specifies the design, conduct, analysis and endpoints of the trial.

Trovax works by targeting the 5T4 antigen—a protein that is found on 85% of solid tumors. The idea is that by targeting this protein Trovax initiates an immune response enabling the body to fight the cancer.

See the Oxford BioMedica website for more information.

Breast cancer

TroVax will be administered after standard chemotherapy to combat Stage III/IV breast cancer to 120 patients, with the key endpoint being progression-free survival compared to historical controls. The United States clinical trial consortium, Southwest Oncology Group has received FDA clearance to start the trial with sponsorship from the United States National Cancer Institute and is expected to begin by end 2006.

Colorectal cancer

TroVax will be administered with adjuvant chemotherapy to combat Stage II/III colorectal cancer to approximately 3000 patients, with the primary endpoint of overall and disease-free survival at three years. Clinical trial network, QUASAR, is seeking funds for the proposed trial through appropriate agencies

Commercialisation strategy

Oxford BioMedica entered a global development and commercialisation agreement for TroVax in March 2007 with sanofi-aventis. There are many aspects to this agreement including co-funding the ongoing TRIST study and funding all other research, development, regulatory and commercialisation activities.