AstraZeneca’s (LON:AZN) Phase III KESTREL study of durvalumab/tremelimumab has potential to show extended survival in patients with first-line recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN), experts said.
Phase I durvalumab monotherapy data lends confidence in the combination’s ability to improve survival over the SOC regimen of Eli Lilly’s (NYSE:LLY) Erbitux (cetuximab)/5-FU/platinum chemotherapy (EXTREME), albeit with some reservations about potential toxicity, experts said.
If KESTREL -- comparing durvalumab with or without tremelimumab against EXTREME -- is successful, experts were uncertain how results would affect SCCHN treatment overall, especially Bristol-Myers Squibb's (NYSE:BMY) Opdivo (nivolumab) and Merck’s (NYSE:MRK) Keytruda (pembrolizumab), which both have approvals for SCCHN after platinum chemotherapy. An expert added that while Opdivo combined with BMS’ CTLA4-targeting Yervoy (ipilimumab) – currently in the Phase III CheckMate-651 study (NCT02741570) and Phase II CheckMate-714 (NCT02823574) for first-line recurrent/metastatic SCCHN – could have the advantage of greater clinical familiarity, KESTREL has a better trial design to potentially show head-to-head data for durvalumab/tremelimumab versus durvalumab monotherapy or EXTREME.
Analysts expect KESTREL data in 2H17, forecasting a 40% probability of success and sales in SCCHN ranging from USD 600m-800m. AstraZeneca announced 27 October 2016 it would abandon pursuit of single-agent durvalumab in SCCHN. AstraZeneca’s idea behind the combination was to differentiate durvalumab from Opdivo and Keytruda given their single-agent approvals in August and November 2016, respectively, added Dr Sara Pai, lecturer on surgery, Massachusetts General Hospital, Boston, who is also an investigator and AstraZeneca advisory board member.