plus PF-3512676 (CPG 7909) in patients with melanoma or advanced solid tumours

receptor-9 agonist, are targeted immune modulators that elicit durable single-agent antitumour activity in advanced cancer. Methods: To determine the maximum tolerated dose (MTD) of these agents combined during this phase I study, patients received intravenous tremelimumab (6.0, 10.0, or 15.0mg kg 1) every 12 weeks plus subcutaneous PF-3512676 (0.05, 0.10, or 0.15mgkg 1) weekly. Primary end points were safety and tolerability; secondary end points included pharmacokinetics and antitumour activity. Results: Twenty-one patients with stage IV melanoma (n 17) or advanced solid tumours (n 4) were enrolled. Injection-site reactions (n 21; 100%), influenza-like illness (n 18; 86%), and diarrhoea (n 13; 62%) were the most common treatment-related adverse events (TAEs). Grade X3 TAEs were reported (n 7; 33%). Dose-limiting toxicities (prespecified 6-week observation) occurred in one of the six patients in the 10mgkg 1 tremelimumab plus 0.05mgkg 1 PF-3512676 cohort (grade 3 hypothalamopituitary disorder) and two of the six patients in the 15mgkg 1 tremelimumab plus 0.05mg kg 1 PF-3512676 cohort (grade 3 diarrhoea). Consequently, 15mgkg 1 tremelimumab plus 0.05mg kg 1 PF-3512676 exceeded the MTD. Two melanoma patients achieved durable (X170 days) partial response. No human antihuman antibody responses to tremelimumab were observed. Conclusion: Weekly PF-3512676 (p0.15mg kg 1) plus tremelimumab (p10mg kg 1 every 12 weeks) was tolerable. Tremelimumab (CP-675 206 or ticilimumab; Pfizer Inc, New York