A trial of talimogene laherparepvec and pembrolizumab for advanced melanoma (MASTERKEY-265)

The following bullet points list the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.

You may be able to join this trial if all of the following apply. You:

• Have melanoma that has spread to other parts of the body and cannot be completely removed by surgery (stage 3b to stage 4)
• Have 1 area of melanoma at least 10 mm across (diameter) that talimogene laherparepvec can be injected into or have a number of smaller areas of melanoma that can be injected into and the total of the diameters of each area adds up to at least 10 mm
• Have at least 1 area of cancer that can be measured on a scan
• Are willing to have a sample of your cancer taken (a biopsy ) if there is no suitable sample available that is less than 3 months old. The biopsy must not have been taken within 3 months of any treatment that reached your whole body (systemic treatment )
• Have satisfactory blood tests results
• Are well enough to carry out your normal activities, apart from heavy physical work (performance status of 0 or 1)
• Are at least 18 years old  
• Are willing to use reliable contraception during treatment and for 3 months after the final dose of talimogene laherparepvec or 4 months after the last dose of pembrolizumab if there is any possibility you or your partner could become pregnant and are willing to use male or female latex condoms during treatment and for 30 days afterwards to avoid the possibility of passing on talimogene laherparepvec

If you have contact with people who have a weakened immune system, have HIV and are pregnant or with children under 1 year, you must take precautions against exposing them to your blood and other bodily fluids (such as your saliva, urine or semen) during the time you have treatment with talimogene laherparepvec and for 28 days afterwards.

You cannot join this trial if any of these apply. You:

• Have melanoma that started in the eye (uveal melanoma) or in the mucosal tissue (mucosal melanoma )
• Developed melanoma after having an organ transplant, leukaemia or you were born with a problem with your immune system and the doctors think your melanoma is linked to these conditions
• Have melanoma spread to the brain that hasn’t been treated (you may be able to join if you have no more than 3 areas of melanoma spread to the brain, have had treatment with surgery, gamma knife therapy  or stereotactic radiotherapy , there is no sign of the areas growing and you haven’t needed steroids for the past 2 months)
• Are due to have any other anti cancer treatment during the time of the trial apart from radiotherapy to manage symptoms (palliative radiotherapy)
• Have had talimogene laherparepvec or any other virus (oncolytic viruses) to treat your cancer
• Have had pembrolizumab or any other similar drug such as nivolumab
• Have had an experimental drug or used an experimental device as part of another clinical trial in the past 28 days
• Have had radiotherapy in the past 28 days
• Have had a cancer drug called interferon, a monoclonal antibody (such as ipilimumab) or chemotherapy given into your arm or leg (regional chemotherapy) in the past 28 days
• Have moderate to severe side effects from previous anti cancer treatments
• Have had a stem cell transplant in the last 5 years using donor stem cells
• Have had a cancer vaccine
• Have had another cancer in the past 3 years apart from successfully treated early cancer (carcinoma in situ ) of the cervix, breast, prostate or bladder, successfully treated non-melanoma skin cancer or any other cancer treated with the aim to cure, no signs of it for at least 3 years and a low risk of it coming back
• Have or have had an autoimmune disease  such as autoimmune pneumonitis, glomerulonephritis, vasculitis or any other autoimmune condition that is causing symptoms or needed treatment that reached your whole body (systemic treatment) in the past 2 years (unless it is vitiligo, childhood asthma that has resolved, thyroid problems that are controlled by medications or treatment that replaces something in the body such as insulin)
• Have a weakened immune system due to another disease such as infection 
• Have taken drugs that damp down your immune system (immunosuppressants) such as steroids in the past 7 days or for more than 2 weeks (unless it was an inhaler)
• Have an herpes infection or a skin lesion (herpetic skin lesion) that needs treatment (such as acyclovir) by mouth or as an injection (the occasional use of creams may be allowed)
• Have had complications caused by herpes infection such as inflammation of the eye (herpetic keratitis) or the brain (encephalitis)
• Are known to be sensitive to talimogene laherparepvec, pembrolizumab or anything it contains
• Have had a live vaccination  in the past 28 days
• Have HIV
• Have hepatitis B or hepatitis C
• Have active tuberculosis (TB)
• Have any other serious medical condition or mental health problem that the trial team think could affect you taking part
• Are pregnant or breast feeding

In some people, their melanoma might have changes to the BRAF gene . If your melanoma is either BRAF wild type or has a BRAF mutation there are some treatments you either cannot have had before starting treatment in this trial or you must have finished the treatment in the last 2 weeks and have recovered from any side effects. The trial team can give you more details.