threatening condition and there are no other established therapies available, approvals have been granted based on non-comparative Phase II studies which used response rate as an endpoint. The indication proposed by the sponsor is: the treatment of unresectable or metastatic melanoma in adults’. ‘for This is a broad indication, which would include patients eligible for treatment with ipilimumab or BRAF inhibitors, even though comparable efficacy has not been demonstrated. The sponsor is currently conducting randomised controlled trials in melanoma comparing pembrolizumab with chemotherapy (Study P002) and ipilimumab (Study P006). It is therefore recommended that pembrolizumab be approved for registration, but with a more restricted indication than the one proposed by the sponsor. The indication currently approved in the USA would be appropriate: the treatment of patients with unresectable or metastatic melanoma and disease ‘for progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.’ The risk-benefit balance is less favourable in subjects with PD-L1 negative disease, due to limited efficacy. It may be appropriate to further limit the indication to subjects with PDL1 positive tumours. However this would require the availability of appropriate testing. The sponsor should be asked to comment on this issue. First round recommendation regarding authorisation It is recommended that the application be approved, but with the restricted indication outlined above. Clinical questions Efficacy Question 1 The sponsor was asked to provide a short summary of any updated/new efficacy data relating to the following: Duration of response in the melanoma cohorts (B1, B2 and D) of P001. Any updated data on duration of response in subjects with PD-L1 negative disease should also be provided Overall survival in the melanoma cohorts (B1, B2 and D) of Study P001 The relationship between biomarkers (other than PD-L1) and efficacy outcomes in melanoma in study P001 Results from Cohort B3 in Study P001 Results from the Phase III melanoma studies P002 and P006. Question 2 The sponsor was asked to comment on the availability in Australia of IHC testing for tumour expression of PD-L1. Are there any plans for the assay used in Study P001 to be made commercially available?
threatening condition and there are no other established therapies available, approvals have been granted based on non-comparative Phase II studies which used response rate as an endpoint. The indication proposed by the sponsor is: ‘for the treatment of unresectable or metastatic melanoma in adults’. This is a broad indication, which would include patients eligible for treatment with ipilimumab or BRAF inhibitors, even though comparable efficacy has not been demonstrated. The sponsor is currently conducting randomised controlled trials in melanoma comparing pembrolizumab with chemotherapy (Study P002) and ipilimumab (Study P006). It is therefore recommended that pembrolizumab be approved for registration, but with a more restricted indication than the one proposed by the sponsor. The indication currently approved in the USA would be appropriate: ‘for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.’ The risk-benefit balance is less favourable in subjects with PD-L1 negative disease, due to limited efficacy. It may be appropriate to further limit the indication to subjects with PDL1 positive tumours. However this would require the availability of appropriate testing. The sponsor should be asked to comment on this issue. First round recommendation regarding authorisation It is recommended that the application be approved, but with the restricted indication outlined above. Clinical questions Efficacy Question 1 The sponsor was asked to provide a short summary of any updated/new efficacy data relating to the following: Duration of response in the melanoma cohorts (B1, B2 and D) of P001. Any updated data on duration of response in subjects with PD-L1 negative disease should also be provided Overall survival in the melanoma cohorts (B1, B2 and D) of Study P001 The relationship between biomarkers (other than PD-L1) and efficacy outcomes in melanoma in study P001 Results from Cohort B3 in Study P001 Results from the Phase III melanoma studies P002 and P006. Question 2 The sponsor was asked to comment on the availability in Australia of IHC testing for tumour expression of PD-L1. Are there any plans for the assay used in Study P001 to be made commercially available?