Li, Xiaoyun

9009 Background: Programmed death-1 (PD-1) is an inhibitory T-cell co-receptor that may lead to suppression of antitumor immunity. Lambrolizumab is a humanized monoclonal IgG4 antibody against PD-1. This study explored the safety and clinical activity of lambrolizumab in patients (pts) with advanced melanoma (MEL). Methods: In this ongoing phase 1b expansion study of MEL pts with or without previous ipilimumab (IPI) treatment, lambrolizumab was administered IV every 2 or 3 weeks until disease progression or unacceptable toxicity. Tumor response was assessed every 12 weeks by independent, central, blinded radiographic review per immune-related response criteria and RECIST 1.1. Results: As of December 1, 2012, 294 pts with MEL were enrolled, including 179 IPI-naive and 115 IPI-pretreated. Pts received lambrolizumab 10 mg/kg (n = 183) or 2 mg/kg (n = 111). Preliminary data from the first 85 consecutive pts dosed before April 25, 2012, who had independent radiologic review available as of December 3, 2012, indicate a confirmed overall response rate per RECIST 1.1 of greater than 35%, pooled across all doses and schedules and including both IPI-naive and IPI-pretreated patients. The median duration of response has not been reached as only 2 pts who had initial response discontinued due to disease progression, but the duration of confirmed responses range from 28+ to 240+ days (up to 8+ months). Among 133 pts who were dosed with lambrolizumab before July 31, 2012, and evaluable for adverse events (AEs) as of September 28, 2012, fatigue (22%), rash (18%), and pruritus (14%) were the most common drug-related AEs (mostly grade 1/2). The incidence of drug-related grade 3/4 AEs was 10% (24% regardless of attribution). Four drug-related cases of pneumonitis were reported, all of grade 1/2. Grade 3/4 drug-related hypothyroidism (n = 1) and hyperthyroidism (n = 1) were noted. Conclusions: Preliminary data suggest that lambrolizumab has significant antitumor activity and is well tolerated with manageable side effects in both IPI-naive and IPI-pretreated MEL pts. These data have led to an ongoing, international, randomized study of lambrolizumab versus chemotherapy in IPI-pretreated MEL. Clinical trial information: NCT01295827.

LBA9000^ Background: The humanized monoclonal IgG4 anti-PD-1 antibody MK-3475 has demonstrated durable antitumor activity in MEL and NSCLC. We evaluated MK-3475 efficacy and safety in a pooled analysis of 411 MEL pts. Methods: A nonrandomized cohort of ipilimumab-naive (IPI-N) and IPI-treated (IPI-T) pts treated with MK-3475 10 mg/kg Q2W, 10 mg/kg Q3W, or 2 mg/kg Q3W and randomized cohorts of IPI-N and IPI-T pts treated with 2 Q3W or 10 Q3W were included. Response was assessed every 12 wk by RECIST 1.1 by independent central review and by immune-related response criteria (irRC) by investigator. Results: 162 pts were treated at 2 Q3W, 192 at 10 Q3W, and 57 at 10 Q2W. 190 pts were IPI-N and 221 were IPI-T. As of the 10/18/2013 cutoff, all pts had ≥6 mo follow-up and >75% had ≥9 mo follow-up. Among the 365 pts with measurable disease at baseline, ORR by RECIST was 40% (95% CI 32%-48%) in IPI-N and 28% (95% CI 22%-35%) in IPI-T pts. Responses were durable (88% ongoing at analysis). Median PFS by RECIST was 24 wk in IPI-N and 23 wk in IPI-T pts. Median OS was not reached, with 1-y OS of 71% in all pts. Benefit was observed by both RECIST and irRC at all doses and schedules in IPI-N and IPI-T pts (Table). MK-3475 demonstrated activity in all major subgroups irrespective of ECOG PS, LDH levels, BRAFmutation, M stage, and number and type of prior therapy. Overall, 12% of pts experienced drug-related grade 3/4 AEs and 4% discontinued due to a drug-related AE. There were no drug-related deaths. Conclusions: MK-3475 showed durable responses and a manageable safety profile across dose and schedules in IPI-N and IPI-T MEL pts. The observed efficacy and safety suggest MK-3475 may be an appropriate treatment for all pts with MEL. Clinical trial information: NCT01295827. [Table: see text]