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Association Between Immune-related Adverse Events (irAEs) And Disease Control Or Overall Survival In Patients (pts) With Advanced Melanoma Treated With 10 Mg/kg Ipilimumab In Three Phase II Clinical Trials

J. Lutzky, J. Wolchok, O. Hamid, C. Lebbe, H. Pehamberger, G. Linette, V. de Pril, R. Ibrahim, A. Hoos, S. O'Day

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9034 Background: The monoclonal antibody ipilimumab targets cytotoxic T-lymphocyte antigen-4. The most common AEs associated with ipilimumab are irAEs, and both antitumor and irAE responses likely reflect its immune-mediated mechanism of action. In this report, a potential association between disease control (DC) or overall survival (OS) and irAEs in patients (pts) with advanced melanoma treated with 10 mg/kg ipilimumab in 3 Phase II clinical trials was explored. Methods: Across 3 Phase II studies (CA184008, 022, and 007), ipilimumab (10 mg/kg) was given every 3 weeks (Q3W) x 4 (induction); eligible pts could continue to receive ipilimumab Q12W starting at week (wk) 24 (maintenance). In study 022, pts were randomized to 0.3, 3, and 10 mg/kg groups, whereas study 008 was a single-arm trial of ipilimumab 10 mg/kg. In study 007, ipilimumab 10 mg/kg was administered either with placebo or daily prophylactic budesonide. Disease control (CR/PR/SD) was evaluated using modified World Health Organization (mWHO) and immune- related response criteria (Hodi FS, et al. J Clin Oncol 26: 2008 (May 20 suppl; abstr 3008). Association between DC and grade 0/1 vs. grade ≥2 irAEs was examined (studies 007, 008, and 022). Association between OS and irAEs which developed within 12 wks of ipilimumab treatment was also explored using landmark analyses from Day 81 (studies 008 and 022). Results: Across the 3 phase II studies, the rate of DC by mWHO in pts with grade 0/1 irAEs was 20–24% and in pts with grade ≥2 irAEs was 34–43%. The number of pts with DC was higher among those who experienced an irAE compared with those who did not, but DC was not statistically significantly associated with grade 0/1 vs grade ≥2 irAEs. For pts who lived up to Day 81 in studies 008 and 022, median OS (95% CI) from Day 81 was 14.8 mo (10.0–21.7) for any irAE and 8.21 mo (5.29–13.7) for no irAE within 12 weeks; median OS was 13.6 mo (5.78-NR) for any grade ≥2 irAE and 11.3 mo (7.95–15.8) for no grade ≥2 irAE within 12 weeks. Conclusions: DC and survival benefits with ipilimumab are observed among pts that develop an irAE and among pts that do not develop an irAE. Thus, pts who do not experience an irAE may still demonstrate clinical benefit with ipilimumab. [Table: see text]