Also at ASCO we presented the results of the 264 study which is a randomised phase II study in patients with stage 3b, 3c and stage 4 melanoma. These are patients that have a dermal subcutaneous or lymph node lesion that we could inject with talimogene laherparepvec, also known as T-VEC. In this study specifically, this was a randomised phase II study in which half the patients received ipilimumab, which is an anti-CTLA-4 antibody, the other half received ipilimumab plus T-VEC. T-VEC, or talimogene laherparepvec, is a herpes simplex type 1 virus that is already FDA approved and it’s a virus that has been shown to have an effect both where we inject it into tumours but also to have a systemic effect. Combining it with ipilimumab we wanted to see if we could have a better effect compared to what we would see with ipilimumab alone. So the primary endpoint for this study was overall response rate, as based on immune related response criteria.
The study met its primary endpoint. In the randomised study, which had about 100 patients in each arm, we found that the response rate in patients treated with ipilimumab alone was 18% whereas the response rate in patients treated with ipilimumab plus T-VEC was 38%, so more than a doubling of the response rate. Specifically we also did a subset analysis and looked at the stage of disease that the patients had, so looking at patients with stage 3b, 3c and stage 4 M1A disease. These are patients who do not yet have liver and lung metastases and other visceral metastases. We found that in this setting there was a further increase in the response rate in patients receiving ipi plus T-VEC versus ipi alone. But also, importantly, as well in patients that did have lung and liver metastases we saw a doubling of the response rate in patients receiving ipi plus T-VEC versus ipilimumab alone.
I personally think that this is a very ground-breaking study. This is a first randomised study using an oncolytic immunotherapy with a checkpoint inhibitor to see responses in patients with metastatic melanoma. So from that perspective the fact that we see an almost 40% response rate is very exciting for this.
Where are we taking this next? We are actually doing an additional study right now where we’re combining T-VEC with pembrolizumab which is an anti-PD-1 inhibitor or antibody. In that setting patients are randomised in a phase III study to receive either T-VEC and pembrolizumab versus a placebo that we inject into the tumour and pembrolizumab. That’s also an important study because the whole question is what does interlesional therapy add to the response rate. By injecting saline or a placebo into those lesions we will have a good idea about the added benefit of using T-VEC with pembrolizumab. This is a large phase III randomised study with 660 patients and a study that we hope to meet accrual within the next year or so. The primary endpoint for that study is actual a dual primary endpoint with progression free survival as well as overall survival.
