dm+d

Unassigned

New Medicines

TroVaxInoperable/unresectable metastatic colorectal cancer, ovarian cancer, prostate cancer and renal cancer

Information

TroVax
Vaccine
Oxford Biomedica
Sanofi

Development and Regulatory status

Phase II Clinical Trials
None
Discontinued
Yes
01. Jul 09: Oxford BioMedica is seeking a partner (as replacement for Sanofi-Aventis) to develop & commercialise MVA 5T4 [3].
02. Jul 09: Oxford BioMedica reported that the US FDA supports the company´s proposal to continue clinical investigations of MVA 5T4 in pts with metastatic disease including colorectal cancer & a number of other cancers. Depending on the outcome of the trials in metastatic disease, the FDA may also allow trials of MVA 5T4 as adjuvant therapy, particularly in pts with colorectal cancer. The company is also seeking clinicians & clinical trial networks to conduct independent trials of MVA 5T4 [3].
03. Nov 10: discussions are ongoing for sponsored trials [3].
04. May 15: PII development in multiple cancer indications is ongoing in the United Kingdom [10]
05. May 15: Potential launch date updated as phase II trials still continuing [8].
06. Jan 17: No further update on development in the UK. US development has been discontinued [11]

Category

Cancer vaccine;immunostimulant: 5T4 is an antigen that is not found in healthy adult tissue, but is present in a high proportion of tumours
Inoperable/unresectable metastatic colorectal cancer, ovarian cancer, prostate cancer and renal cancer
Intramuscular

Trial or other data

01. The P3 QUASAR V study expected to start enrolling 3000 patients with early-stage (stage II/III) colorectal cancer in mid-2008. The vaccine will be used during or after adjuvant chemotherapy with a primary endpoint of disease-free survival at three years. This stusy will be conducted by the UK-based clinical trial network, QUASAR (1).
02. A P3 study, FLAMENCO, in patients with metastatic colorectal cancer trial will evaluate MVA 5T4 as a first-line treatment in association with FOLFOX or FOLFIRI (+/- bevacizumab) in 1300 patients with metastatic colorectal cancer. The study will start to enroll in mid-2008 and results from an interim analysis are expected in 2010. A submission for regulatory approval in this indication is scheduled for 2013 (1).
03. Apr 09: Sanofi Aventis return rights to Oxford Biomedica following a pipeline review (2).
04. Mar 11: Oxford Biomedica announces that PIII TRIST results (in renal cancer), published in Clinical Cancer Research in Nov 10, confirmed the association between a high 5T4 antibody response & enhanced survival in pts treated with TroVax. They have identified an algorithm (the “Immune Response Surrogate”; IRS) for predicting the quantitative 5T4 antibody response induced by TroVax in order to identify those pts who are most likely to mount a strong 5T4 antibody response before receiving TroVax. The IRS is a combination of three baseline (pre-treatment) blood parameters which can be measured using a blood test; 5T4 antibody levels, haemoglobin & haematocrit (the proportion of blood volume occupied by red blood cells). Pts with higher IRS values who were treated with TroVax survived longer than pts in the placebo gp with the same IRS values. Importantly, the IRS was also associated with 5T4 antibody response & survival when applied to an independent dataset derived from the nine historic PI & II studies of TroVax in pts with renal, colorectal & prostate cancer, implying that the IRS could potentially be applied to multiple cancer types. The IRS will be used in all future TroVax clinical trials including the planned sponsored PII studies in colorectal cancer expected to start in 2011. Based on the typical blood profiles of pts with these cancer indications, it is expected that the IRS will predict that the majority of these pt populations may benefit from TroVax [4].
05. Sanofi-Aventis had planned to start the PIII FLAMENCO study but discontinued their involvement. The funding of the PIII QUASAR V trial derives from a variety of sources, including the UK Medical Research Council & the UK Department of Health [3]. No news is available on the progress of either trial [3,5,6].
06. Jul 12: Cardiff University in partnership with Oxford Biomedica have enrolled first patient into a phase II trial (TaCTiCC) of MVA 5T4 in patients with colorectal cancer. Up to 54 patients will be randomised to receive MVA 5T4 alone or in combination with cyclophosphamide. The primary endpoint of trial is to assess anti-5T4 immune responses following treatment. Secondary endpoints include progression-free survival, objective response rate and overall survival [7]. The planned closure date of trial is Dec 15 [8].
07. Nov 15: PII trial in Mesothelioma (Combination therapy, First line therapy) in the United Kingdom is completed (NCT01569919)[10]