• A Phase Ib dose-escalation study of MEDI4736 in combination with tremelimumab established a recommended dose and schedule for Phase III trial development that yielded manageable, generally reversible adverse events overall.
• The ongoing Phase III ARCTIC trial is evaluating MEDI4736 as monotherapy or in combination with tremelimumab in patients with advanced NSCLC who have received at least 2 prior systemic treatment regimens.
• In an ongoing Phase I trial of pembrolizumab and ipilimumab in locally advanced or metastatic NSCLC, the combination demonstrated antitumor activity and a manageable toxicity profile, with no dose-limiting toxicities or treatment-related deaths.
• The Phase I CheckMate 012 trial of first-line nivolumab in combination with ipilimumab for patients with advanced NSCLC demonstrated a high level of clinical activity characterized by deep and durable responses.

During the ASCO plenary session, we saw more favorable data on the use of an anti-PD-1 antibody combined with an anti-CTLA-4 antibody in melanoma, and the same strategy is being studied in lung cancer. Early findings from trials using this strategy unveiled at ASCO included a Phase I study of 18 patients receiving the combination of pembrolizumab and ipilimumab that demonstrated a response rate of 39%. Another Phase Ib/II dose-finding study evaluated MEDI4736 and tremelimumab and demonstrated an objective response in more than a quarter of patients with 22% experiencing a Grade 3 or 4 adverse event. A third data set presented more recently at IASLC showed promising activity with the combination of nivolumab and ipilimumab as first-line therapy with a low frequency of Grade 3 and 4 adverse events leading to treatment discontinuation. Although the benefits of combination therapy versus monotherapy in melanoma seem to be greatest in patients with low PD-L1 tumor expression, data on this question in lung cancer are incomplete at this point.

One of the concerns with these combinations is the increased rate of toxicity, which to date has generally been considered manageable. An important ongoing Phase III trial is evaluating the combination of MEDI4736 and tremelimumab in patients both with and without PD-L1 expression who have received at least 2 prior therapies.