Phase III data for Amgen’s cancer-killing virus product talimogene laherparepvec (T-VEC) back what could be a potential advance in the treatment of melanoma.
The results of the OPTiM study – reported at the American Society of Clinical Oncology (ASCO) meeting in Chicago – are a milestone as they represent the first time that a virus-based therapy has been shown to provide clinical benefit in this form of skin cancer.
In OPTiM, the virus achieved a durable response rate – defined as a complete or partial tumour response lasting six months or more – in around 16 per cent of metastatic melanoma patients, compared to just 2 per cent with granulocyte macrophage colony-stimulating factor (GM-CSF) therapy.
Patients with milder disease tended to fare even better, with durable response rates of more than 30 per cent. Meanwhile, the overall response rate was 26 per cent with T-VEC compared to 6 per cent for GM-CSF, and there was also a trend toward improved overall survival with Amgen’s drug.
Interim data revealed that median overall survival reached 23.3 months with T-VEC versus 19 months with GM-CSF. Patients in the trial continue to be followed and Amgen said it would have more insight on survival later this year.
T-VEC has a double-whammy effect on cancer cells, infecting and killing some cells directly while also eliciting an immune response that tackles other tumour tissue. After injection into the tumour the virus replicates and secretes GM-CSF locally, which leads to cell rupture and, in turn, helps stimulate the host response.
While the results were well-received, questions have been raised about the choice of comparator drug in the trial. While GM-CSF makes sense from a biological perspective based on T-VEC’s mechanism of action, it is not a standard treatment for melanoma.
Adding GM-CSF to Bristol-Myers Squibb’s (BMS) CTLA-4 inhibitor Yervoy (ipilimumab) did however make a dramatic difference to the activity of the drug in a phase II study presented at ASCO. The combination prolonged overall survival versus Yervoy given alone, allowing two thirds of patients to live beyond 12 months, and GM-CSF also appeared to reduce the toxicity of BMS’ drug.
For T-VEC, interest is building around the concept of combining the virus with PD-1-targeting immunotherapies such as BMS’ nivolumab and Merck & Co’s lambrolizumab, which also generated new data at ASCO. Amgen said it is carrying out early-stage combination studies with T-VEC.
Amgen acquired T-VEC in 2011 when it bought BioVex in a deal valued at up to $1bn, including $425m in upfront cash.
Melanoma accounts for less than five per cent of skin cancers but is by far the most aggressive form of the disease, accounting for 75 per cent of all skin cancer-related deaths each year.
Treatment of the cancer has already undergone something of a revolution since the debuts of Yervoy and Roche’s Zelboraf (vemurafenib) in 2011, with both drugs achieving more than $200m in sales in their first full year on the market.