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Background D+T has been approved for several indications, including BRAF V600–mutant unresectable or metastatic melanoma and as adjuvant therapy following resected BRAF V600–mutant stage III melanoma. Pyrexia is a common adverse event but is generally low-grade and manageable; further characterization may optimize management and reduce permanent treatment (tx) discontinuation due to pyrexia. Methods Trial databases were queried for reports of pyrexia in pts treated with D and/or T, including adjuvant therapy. Indications included unresectable, metastatic, or resected stage III melanoma; non-small cell lung cancer (NSCLC); colorectal cancer, and other BRAF–mutation positive solid tumors. Data for D+T was compiled from the following trials: COMBI-AD (NCT01682083), COMBI-d (NCT01584648), COMBI-v (NCT01597908), and BRF113928 (NCT01336634). Pyrexia was graded according to the Common Terminology Criteria for Adverse Events version 4.0. Results A total of 1991 pts were included from clinical trials (D+T, n=1076; D, n=586; T, n=329). Pyrexia was observed in 904 pts: D+T, 61% (660/1076); D, 33% (196/586); T, 15% (48/329). Of pts treated with D+T, 6% (62/1076) experienced grade 3 events and 1 of 1076 pts experienced a grade 4 event. The median time to onset was 27 d (range, 1-716 d). Recurrent any-grade pyrexia occurred in 41% (442/1076) of pts; 29% had ≥ 3 episodes. Of the 442 pts with recurrent pyrexia, 377 (85%) experienced a subsequent event within 3mo of the first pyrexia episode. No pyrexia-related deaths were reported. Outcomes were reported for 2252 of 2253 events in pts treated with D+T across trials. Pyrexia management strategies included: tx interruption (939/2253 events [42%]), dose reduction (225/2253 [10%]), and tx discontinuation (62/2253 [3%]); ≥ 98% of events were reported to be resolved following each of the aforementioned interventions. Conclusions Pyrexia in pts treated with D+T is typically low-grade, occurs early during tx exposure, and most pts experience ≤ 1 episode. Tx interruption was the most frequent intervention strategy used in clinical trials. Pyrexia can be effectively managed with nearly all events reported to have been resolved at the time of the analysis. Clinical trial identification Pooled analysis of data from the following trials: NCT01227889, NCT01153763, NCT01266967, NCT01072175, NCT00880321, NCT01336634, NCT01584648, NCT01597908, NCT01682083, NCT01245062, NCT01037127, NCT00687622. Editorial acknowledgement Allison Lytle, PhD, from ArticulateScience LLC, funded by Novartis Pharmaceuticals Corporation. Legal entity responsible for the study Novartis Pharmaceuticals Corporation. Funding Novartis Pharmaceuticals Corporation. Disclosure C. Robert: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Array; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Merck. D. Schadendorf: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Immunocore; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Incyte; Honoraria (self), Advisory / Consultancy: 4SC; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Honoraria (self), Advisory / Consultancy: Mologen; Advisory / Consultancy: Sanofi/Regeneron; Speaker Bureau / Expert testimony: Roche; Travel / Accommodation / Expenses: Merck; Honoraria (self): Sysmex; Honoraria (self): Grunenthal Group; Honoraria (self): Agenus; Honoraria (self): Array BioPharma; Honoraria (self): AstraZeneca; Honoraria (self): LEO Pharma; Honoraria (self): Pfizer; Honoraria (self): Philogen; Honoraria (self): Regeneron. R. Dummer: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Novartis; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Merck Sharp & Dhome; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Bristol-Myers Squibb; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Roche; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Amgen; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Takeda; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Pierre Fabre; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Sun Pharma; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Sanofi; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship: Catalym. K.T. Flaherty: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Genentech; Advisory / Consultancy: Merck; Advisory / Consultancy: Lilly; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Oncoceutics; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: Aeglea Biotherapeutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Loxo; Advisory / Consultancy: Roche; Advisory / Consultancy: Asana Biosciences; Advisory / Consultancy: Incyte; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Shattuck Labs; Advisory / Consultancy: Tolero Pharmaceuticals; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy, Shareholder / Stockholder / Stock options: FOGPharma; Advisory / Consultancy: Neon Therapeutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Tvardi; Advisory / Consultancy: Takeda; Advisory / Consultancy: Varestem; Advisory / Consultancy: Boston Biomedical; Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy: Cell Medica; Advisory / Consultancy, Travel / Accommodation / Expenses: Debiopharm Group; Shareholder / Stockholder / Stock options: Clovis Oncology; Shareholder / Stockholder / Stock options: X4 Pharma; Shareholder / Stockholder / Stock options: PIC Therapeutics; Shareholder / Stockholder / Stock options: Fount Therapeutics; Shareholder / Stockholder / Stock options: Apricity Health; Shareholder / Stockholder / Stock options: Vivid Biosciences; Shareholder / Stockholder / Stock options: Checkmate Pharmaceuticals; Shareholder / Stockholder / Stock options: Strata Oncology. H.A. Tawbi: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): GlaxoSmithKline; Advisory / Consultancy: Roche; Advisory / Consultancy: Array; Research grant / Funding (institution): Celgene. A.M. Menzies: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre. A. D'Amelio: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis; Shareholder / Stockholder / Stock options: GlaxoSmithKline. E. de Jong: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. E. Gasal: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. G.V. Long: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Novartis; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Pierre Fabre.

Background A goal of adjuvant therapy is to prolong disease-free survival, with the risk of mortality approaching that of the general population. From the literature, recurrences in stage III melanoma are most likely to occur within 3 years after surgery. Mixture-cure models (MCMs) capture survival heterogeneity of cancer patients by assuming they are either “cured” or “uncured”, where cured patients are defined as having a low risk of relapse. Methods We applied MCMs to 3-year recurrence-free survival (RFS) outcomes in patients with resected melanoma treated with adjuvant nivolumab (NIVO) or ipilimumab (IPI) in the double-blind, phase III CheckMate 238 trial (NCT02388906) and assumed that the cured fraction has mortality risks similar to that of the general population. Patient age, sex, and geographic region information from CheckMate 238 and mortality rates from the World Health Organization were used to derive a cohort-level background survival distribution representative of “cured” or “disease-free” patients. Parametric functions were used to model uncured population outcomes. Parameters of the MCM were estimated by means of maximum likelihood methods. Statistical goodness-of-fit metrics and visual inspection showed that generalized gamma and log-logistic distributions were best suited for survival analyses of cured and uncured patients, respectively. Results The 3-year RFS rates were explained by the fraction of patients with a low risk of relapse in the NIVO arm at 55.1% (95% CI, 49.2–60.1) and IPI arm at 39.9% (95% CI, 33.6–46.1). Sensitivity analyses indicated that the estimated fraction of patients with a low risk of relapse was > 50% in the NIVO arm. Estimated RFS distributions of the uncured patients exhibited similar patterns for both arms, implying the differences in RFS rates between treatment arms can be explained with the elicited differences in proportions of patients at high vs low risk of relapse. Conclusions MCM analyses from CheckMate 238 suggested that adjuvant treatment with NIVO leads to a higher proportion of patients with low risk of relapse compared with IPI. Validation of the results from MCMs will include analyses of longitudinal RFS and overall survival data from the EORTC 18071 trial. Clinical trial identification NCT02388906. Editorial acknowledgement Kakoli Parai, PhD, and Andrea Lockett at StemScientific, an Ashfield Company, funded by Bristol-Myers Squibb. Legal entity responsible for the study Bristol-Myers Squibb. Funding Bristol-Myers Squibb. Disclosure J.S. Weber: Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy, Shareholder / Stockholder / Stock options: AltorBioScience; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution): Astellas Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Licensing / Royalties, Named on a patent for a PD-1 antibody biomarker: Biodesix; Shareholder / Stockholder / Stock options: Biond; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: cCam Biotherapeutics; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Celldex; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Daiichi Sankyo; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: GlaxoSmithKline; Honoraria (self), Advisory / Consultancy: Ichor Medical Systems; Research grant / Funding (institution): Incyte; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Lion Biotechnologies; Honoraria (self), Advisory / Consultancy: Medivation; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Licensing / Royalties, Named on patent for an ipilimumab biomarker: Moffitt Cancer Center; Honoraria (self), Advisory / Consultancy: Nektar; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pieris Pharmaceuticals; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Sellas Life Sciences; Honoraria (self), Advisory / Consultancy: WindMIL; Honoraria (self), Advisory / Consultancy, Shareholder / Stockholder / Stock options: CytomX Therapeutics; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis. M. Kurt: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. M. Edmondson-Jones: Advisory / Consultancy: Bristol-Myers Squibb. A. Amadi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. M. Lobo: Full / Part-time employment: Bristol-Myers Squibb. A. Moshyk: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. S. Kotapati: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. P. Mohr: Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: GlaxoSmithKline; Honoraria (self), Advisory / Consultancy: Merck, Sharp & Dohme; Honoraria (self), Advisory / Consultancy: Merck Germany; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Sanofi.

Background Outcome of high-risk stage III melanoma patients (pts) was poor with a 5-year OS rate of Methods Between Augustus 2015 and October 2016, 20 stage IIIB/IIIC melanoma pts with palpable nodal disease were included in the phase Ib feasibility OpACIN trial. Pts were randomized to receive IPI 3 mg/kg + NIVO 1 mg/kg, either adj 4 courses or split 2 courses neoadj and 2 adj. Path response, as reviewed by a blinded pathologist, was defined as Results After a median FU of 36.7 months (minimum 28.3 months FU of pts alive) none of the 7 pts with a path response in the neoadj arm have relapsed. Both non-responding pts in the neoadj have relapsed versus 4 pts in the adj arm. One pt has died in the neoadj arm and 3 in the adj arm. The estimated 3-year RFS rate was 80% for the neoadj arm and 60% for the adj arm. The 3-year OS rates were 90% and 67%, respectively. Of the 18 (90%) pts that had developed 1 or more grade 3-4 adverse events all have recovered to ≤ grade 1, except for grade 2 endocrine toxicities needing hormonal supplementation therapy that are ongoing in 8 (50%) of 16 pts alive. Conclusions OpACIN was the first trial investigating neoadj IPI + NIVO in pts with macroscopic stage III melanoma, thus having the longest FU. At 3 years FU, no new safety events occurred and none of the pts with a path response have relapsed, suggesting that path response could be considered as surrogate marker for RFS and OS in neoadjuvant checkpoint inhibitor trials. Clinical trial identification NCT02437279. Legal entity responsible for the study Netherlands Cancer Institute. Funding BMS. Disclosure C.U. Blank: Advisory / Consultancy: MSD; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Roche; Advisory / Consultancy: GSK; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: GenMab; Advisory / Consultancy: Lilly; Research grant / Funding (institution): NanoString; Advisory / Consultancy: Pierre Fabre. J.V. van Thienen: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis. J.B.A.G. Haanen: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AZ/MedImmune; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Immunocore; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy, Research grant / Funding (institution): Neon Therapeutics; Advisory / Consultancy: Celsius Therapautics; Advisory / Consultancy: Gadet; Advisory / Consultancy: GSK. A.C.J. van Akkooi: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: MSD Merck; Advisory / Consultancy: Merck-Pfizer; Advisory / Consultancy: 4SC. T.N. Schumacher: Advisory / Consultancy: Adaptive Biotechnologies; Advisory / Consultancy, Shareholder / Stockholder / Stock options: AIMM Therapeutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Allogene Therapeutics; Advisory / Consultancy: Amgen; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Merus; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Neon Therapeutics; Advisory / Consultancy: Scenic Biotech; Research grant / Funding (institution): MSD; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Merck KGaA; Shareholder / Stockholder / Stock options: Neogene Therapeutics; Shareholder / Stockholder / Stock options, Venture partner: Third Rock Venture. E.A. Rozeman: Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: NanoString. All other authors have declared no conflicts of interest.

Background In the multi-center investigator-initiated OpACIN-neo trial, patients (pts) with macroscopic stage III melanoma were randomized (stratified by center) to 3 different dosing schemes of neoadjuvant (neoadj) IPI+NIVO. Two cycles IPI 1mg/kg + NIVO3mg/kg was identified as the most favorable regimen with 20% grade 3-4 adverse events and a pathological response rate (pRR) of 77%. After a median follow-up (FU) of 8.3 months (mo) none (0/86) of the pts with a pathologic (path) response had relapsed, while 9/21 (43%) without a path response relapsed. Post-hoc analyses were conducted to investigate potential differences between pts treated in Europe (EU) and in Australia (AUS). Methods Baseline patient characteristics, safety and efficacy in terms of path response were evaluated in pts treated in EU (n=48) and AUS (n=38). Multivariate analyses were performed using logistic regression method. Median FU was 9.3mo for EU pts and 6.9mo for AUS pts. Results Baseline characteristics (AUS vs EU) differed in age (median 60 vs 53 year [yr], p=0.017) and AUS pts were more likely to be male (65.8 vs 50.0%, p=0.142) and have an unknown primary melanoma (36.8 vs 20.8%, p=0.100); no difference in PD-L1 expression was observed. There was a trend to a higher pRR for AUS pts than for EU pts (84.2% vs 68.1%, OR 2.50, p=0.092). pRR was also higher for pts >60yr compared to £60yr (91.2% vs 64.7%, OR 5.64, p=0.010) and males vs females (83.7% vs 63.9%, OR 2.90, p=0.041). Multivariate analysis including continent, age and gender showed an adjusted OR for path response of 1.85 (p=0.289) for AUS vs EU pts, an OR of 4.89 (p=0.021) for pts >60yrs vs £60yrs and an OR of 2.50 (p=0.095) for males vs females. The frequency of high grade toxicity was the same in pts 60yr (42.3% vs 32.4%, p=0.353). Conclusions The continental difference in path response appears mostly driven by differences in age and gender. It remains to be elucidated whether the higher pRRs in elderly pts and pts from AUS can be explained by differences in mutational burden (analysis in progress and will be presented). Our data also indicate that neoadj IPI+NIVO is safe and highly effective in the elderly. Clinical trial identification NCT02977052. Legal entity responsible for the study Netherlands Cancer Institute. Funding BMS. Disclosure E.A. Rozeman: Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: NanoString. A.M. Menzies: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre. R.A. Scolyer: Advisory / Consultancy: MSD; Advisory / Consultancy: Neracare; Advisory / Consultancy: Novartis. A.C.J. van Akkooi: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Merck MSD; Advisory / Consultancy: Merck-Pfizer; Advisory / Consultancy: 4SC. J. Hansson: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis. G.V. Long: Advisory / Consultancy: Aduro; Advisory / Consultancy: Amgen; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck MSD; Advisory / Consultancy: Mass-Array; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche. C.U. Blank: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Pfizer; Advisory / Consultancy: GSK; Advisory / Consultancy: GenMab; Research grant / Funding (institution): NanoString. All other authors have declared no conflicts of interest.

Aim: Ipi, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 to augment antitumor immune responses, is an approved treatment for advanced melanoma. We report primary efficacy data and ongoing analyses from a phase III trial to evaluate Ipi as an adjuvant therapy for resected stage III melanoma at high risk of recurrence. Methods: In this randomized, double-blind trial, eligible patients (pts) included those ≥18 yrs of age who underwent complete resection of stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis). 951 pts were randomized (stratified by stage and region) 1:1 to Ipi 10 mg/kg (n = 475) or placebo (Pbo, n = 476) q3w for 4 doses, then every 3 mos for up to 3 yrs until completion, disease recurrence, or unacceptable toxicity. The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included safety and health-related QoL. Results: Overall, 20%/44%/36% of pts had stage IIIA/IIIB/IIIC, 42% ulcerated primary, and 58% macroscopic lymph node involvement. At a median follow-up of 2.7 yrs, Ipi significantly improved RFS vs Pbo (234/475 vs 294/476 events): median RFS 26.1 mos for Ipi vs 17.1 mos for Pbo (HR 0.75, 0.64–0.90; log-rank P = 0.0013). 3-yr RFS rates were 46.5% and 34.8%, respectively. RFS benefit was consistent across subgroups (e.g., stage IIIB or IIIC, ulcerated primary). Most common grade 3/4 immune-related adverse events (irAEs) in the Ipi and Pbo arms were gastrointestinal (15.9% vs 0.8%), hepatic (10.6% vs 0.2%), and endocrine (8.5% vs 0%). Most irAEs were managed and resolved using established algorithms. Of 471 pts who started Ipi, 245 (52%) discontinued treatment due to AEs (182 [38.6%] within 12 weeks); 5 (1.1%) died due to drug-related AEs. RFS analyses adjusted for prognostic factors and key HRQoL data will be presented. Conclusions: In this phase III trial, Ipi as adjuvant therapy provided a clinically and statistically significant improvement in RFS vs Pbo for pts with stage III melanoma at high risk of recurrence. AE profile was generally consistent with that observed in advanced melanoma, although with a higher incidence of endocrinopathies. Disclosure: A.M.M. Eggermont: Financial interest: Advisory boards for Amgen, Bristol-Myers Squibb, GlaxoSmithKline, MedImmune, and MSD; V. Chiarion-Sileni: Advisory board participation: Bristol-Myers Squibb, GlaxoSmithKline, and Roche; J.-. Grob: Consultant or advisory role: Bristol-Myers Squibb, Roche, GlaxoSmithKline, Merck; honoraria: Bristol-Myers Squibb, Roche, GlaxoSmithKline, Merck; R. Dummer: Consultant or advisory role, honoraria, and research funding: AstraZeneca, Novartis, Cephalon, MSD, Bristol-Myers Squibb, GlaxoSmithKline, Roche, Amgen, Bayer; J.D. Wolchok: Grants and personal fees: Bristol-Myers Squibb, during conduct of the study; grants and personal fees from Medimmune, Glaxo SmithKline; personal fees: Merck Sharpe and Dohme, EMDSerono, Johnson and Johnson; H. Schmidt: Advisory board: Roche; speakers' bureau: Bristol-Myers Squibb; O. Hamid: Consultant or advisory role: Bristol-Myers Squibb; speakers' bureau: Bristol-Myers Squibb; research funding from Bristol-Myers Squibb to The Angeles Clinic; C. Robert: Consultant or advisory role: Bristol-Myers Squibb, GlaxoSmithKline, Roche, MSD; honoraria: Bristol-Myers Squibb, GlaxoSmithKline, Roche; P.A. Ascierto: Consultant or advisory role: Bristol-Myers Squibb, Roche-Genentech, MSD, GlaxoSmithKline, Novartis, Ventana; honoraria: Bristol-Myers Squibb, Roche-Genentech, GlaxoSmithKline; research funding: Bristol-Myers Squibb, Ventana; J.M. Richards: Stock ownership: Bristol-Myers Squibb; C. Lebbe: Advisory boards: Bristol-Myers Squibb, Roche, Novartis, GlaxoSmithKline, Amgen.; M. Smylie: Consultant or advisory role: Bristol-Myers Squibb; honoraria: Bristol-Myers Squibb; J.S. Weber: Advisory boards: Bristol-Myers Squibb (less than 10,000 USD annually for advisory boards); grants from Bristol-Myers Squibb to Moffitt for the conduct of the trial in question; M. Maio: Consultant or advisory role: Bristol-Myers Squibb; honoraria: Bristol-Myers Squibb; research funding: Bristol-Myers Squibb; C. Konto: Employee of Bristol-Myers Squibb; V. De Pril: Employee of Bristol-Myers Squibb; stock ownership: Bristol-Myers Squibb; A. Testori: Consultant or advisory role: Bristol-Myers Squibb, Roche, GlaxoSmithKline, Amgen, Celgene; honoraria: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.