1259TiP A randomized, double-blind, placebo-controlled, phase III study comparing the combination of PDR001, dabrafenib and trametinib versus placebo, dabrafenib and trametinib in previously untreated patients with unresectable or metastatic BRAF V600–mutant melanoma (COMBI-i) E. Gasal 1 , A.M. Arance Fernandez 2 , P.A. Ascierto 3 , V. Atkinson 4 , R. Dummer 5 , K.T. Flaherty 6 , J-J. Grob 7 , J. Hansson 8 , J. Hassel 9 , J. Larkin 10 , C. Lebbe ´ 11 , G.V. Long 12 , P. Lorigan 13 , W. Miller 14 , P. Nathan 15 , A. Ribas 16 , C. Robert 17 , D. Schadendorf 18 , H. Tawbi 19 , A. Upalawanna 20 1 Medical Oncology, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, 2 Department of Medical Oncology, Hospital Cl  ınic Barcelona, Barcelona, Spain, 3 Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy, 4 Department of Medical Oncology, University of Queensland, Brisbane, Australia, 5 Department of Dermatology, University of Zurich Hospital, Zurich, Switzerland, 6 Medicine, Dana-Farber Cancer Institute/Harvard Medical School and Massachusetts General Hospital Cancer Center, Boston, MA, USA, 7 Dermatology, Aix-Marseille University and APHM Hospital CHU Timone, Marseille, France, 8 Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden, 9 Department of Dermatology and NCT, Universit€ at Heidelberg, Heidelberg, Germany, 10 Medicine, Royal Marsden Hospital, London, UK, 11 APHP Dermatology and CIC Departments, Ho ˆpital Saint-Louis University Paris Diderot, Paris, France, 12 Melanoma Medical Oncology, Melanoma Institute Australia, University of Sydney, and Mater Hospital, Sydney, Australia, 13 Division of Molecular & Clinical Cancer Sciences, The Christie NHS Foundation Trust, Manchester, UK, 14 Departments of Oncology and Medicine, McGill University, Montreal, QC, Canada, 15 Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, UK, 16 Department of Medicine, UCLA Medical Center, Los Angeles, CA, USA, 17 Department of Medicine, Gustave Roussy Comprehensive Cancer Center, Villejuif–Paris Sud, France, 18 Department of Dermatology, University Hospital Essen and German Cancer Consortium, Essen, Germany, 19 Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 20 Medical Oncology, Novartis Pharma AG, Basel, Switzerland Background: Checkpoint inhibitor and targeted therapies are both important tools in the management of BRAF V600–mutated unresectable or metastatic melanoma. Although these therapies have improved responses and overall survival, many patients still progress and die from this disease. Thus, additional treatment strategies are needed to improve durability of responses and related long-term outcomes in these patients. Based on preclinical and preliminary clinical data, BRAF and MEK inhibitors can re- verse the oncogenic BRAF-induced immune-suppressive phenotype through enhanced melanoma antigen expression and enhanced tumor antigen-specific T-lymphocyte rec- ognition in vivo. These data suggest that there is potential clinical benefit in combining dabrafenib and trametinib with checkpoint inhibitor therapy. Trial design: The 3-part COMBI-i phase 3 study (NCT02967692) will evaluate the safety and efficacy of PDR001, an investigational anti–programmed death 1 antibody, in combination with dabrafenib and trametinib in previously untreated patients with BRAF V600–mutated unresectable or metastatic melanoma. In part 1, a safety run-in will establish the recommended phase 3 regimen (RP3R) for use in part 3 using an adaptive Bayesian logistic regression model. In part 2, tissue and blood samples from the biomarker cohort will be used to characterize baseline immune markers and explore potential immune marker modulation by the triplet therapy. Part 3 is the randomized, double-blind, placebo-controlled portion that will open once the RP3R has been deter- mined. Approximately 500 patients will be randomized 1:1 to receive either PDR001 in combination with dabrafenib and trametinib or placebo in combination with dabrafe- nib and trametinib, with randomization stratified based on Eastern Cooperative Oncology Group performance status and lactate dehydrogenase level. The primary endpoint will be progression-free survival per investigator’s assessment according to RECIST v1.1. Overall survival will be a key secondary endpoint. Clinical trial identification: NCT02967692 First received: November 16, 2016 Legal entity responsible for the study: Novartis Pharmaceuticals Corporation Funding: Novartis Pharmaceuticals Corporation Disclosure: E. Gasal: Employment: Novartis Stock or Other Ownership: Amgen Inc, Novartis. A.M. Arance Fernandez: Honoraria, Consulting/Advisory Role, and Speakers Bureau: Roche, Bristol-Myers Squibb, MSD, and Novartis Travel/Accommodations/ Expenses: Roche, Bristol-Myers Squibb P.A. Ascierto: Consulting/Advisory Role: Bristol-Myers Squibb, Roche/Genentech, Merck Sharp & Dohme, Novartis, Amgen, Array BioParma, Merck Serono Research Funding: Bristol-Myers Squibb, Roche/ Genentech, Array BioPharma. V. Atkinson: Honoraria and Speakers Bureau: Bristol- Myers Squibb, MSD, Novartis, Roche Consulting/Advisory Role: Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre Travel/Accommodations/Expenses: Bristol- Myers Squibb, MSD, Novartis. R. Dummer: Honoraria and Consulting/Advisory Role: Roche, Bristol-Myers Squibb, MSD, Novartis, GlaxoSmithKline, Amgen, Takeda, Pierre Fabre Research Funding: Roche, GlaxoSmithKline, Bristol-Myers Squibb, Novartis, MSD, Takeda, Pierre Fabre. K.T. Flaherty: Consulting/Advisory Role: Novartis. J-J. Grob: Honoraria and Consulting/Advisory Role: Bristol-Myers Squibb, Roche, MSD, Novartis Speakers Bureau: Novartis Travel/Accommodations/Expenses: Bristol-Myers Squibb, MSD, Roche, Novartis. J. Hansson: Consulting/Advisory Role: Roche, Novartis, Merck, Bristol-Myers Squibb Travel/Accommodations/Expenses: Novartis. J. Hassel: Honoraria: Bristol-Myers Squibb, MSD, Roche, GlaxoSmithKline, Novartis, Amgen Research Funding: Bristol-Myers Squibb Travel/Accommodations/ Expenses: Bristol-Myers Squibb, MSD, Amgen, GlaxoSmithKline. J. Larkin: Honoraria: Bristol-Myers Squibb, MSD, Pfizer, Novartis, Eisai, GlaxoSmithKline, Roche Research Funding: Bristol-Myers Squibb, MSD, Pfizer, Novartis. C. Lebbe ´: Honoraria, Consulting/Advisory Role: Roche, Bristol-Myers Squib, Novartis, Amgen, MSD Speakers Bureau: Bristol-Myers Squib, Amgen, Roche, Novartis Research Funding: Roche, Bristol-Myers Squib Travel/Accommodations/Expenses: Roche, Bristol-Myers Squib, Amgen. G.V. Long: Consulting/Advisory Role: Bristol-Myers Squibb, Merck, Novartis, Amgen, Roche P. Lorigan: Consulting/Advisory Role: Merck Sharp & Dohme, Bristol-Myers Squibb, Novartis, Amgen, GlaxoSmithKline Speakers Bureau: Merck Sharp & Dohme, Novartis, Bristol-Myers Squibb, Roche Travel/ Accommodations/Expenses: Merck Sharp & Dohme, Bristol-Myers Squibb. W. Miller: Honoraria: Bristol-Myers Squib, Merck, Roche, Novartis, GlaxoSmithKline Consulting/Advisory Role: Bristol-Myers Squib, Merck, Roche, Novartis, Amgen, GlaxoSmithKline Research Funding: Bristol-Myers Squib, Novartis, GlaxoSmithKline, Roche, AstraZeneca, Merck, MethylGene, Bayer, Amgen, MedImmune. P. Nathan: Consulting/Advisory Role: AztraZeneca, Bristol-Myers Squibb, MSD, Immunocore, Pfizer, Pierre Fabre, Novartis, GlaxoSmithKline, Ispen Speakers Bureau: Bristol-Myers Squibb, Novartis Travel/Accommodations/Expenses: Bristol-Myers Squibb, MSD. A. Ribas: Consulting/Advisory Role: Merck, Amgen, Genentech/Roche, Novartis, Lilly Stock or Other Ownership: Kite Pharma, Compugen, FLX Bio, CytomX Therapeutics, Arcus Ventures. C. Robert: Honoraria and Consulting/Advisory Role: Bristol-Myers Squibb, Roche, Merck, Novartis, Amgen, GlaxoSmithKline. D. Schadendorf: Honoraria, Speakers Bureau and Travel/Accommodations/Expenses: Amgen, Bristol- Myers Squibb, Novartis, MSD, Roche Consulting/Advisory Role: Bristol-Myers Squibb, Novartis, MSD, Roche, Array Research Funding: Bristol-Myers Squibb, Novartis. H. Tawbi: Consulting/Advisory Role: Novartis Research Funding: Bristol- Myers Squibb, Novartis, Merck. A. Upalawanna: Employment and Stock or Other Ownership: Novartis. 1260TiP Late physical, psychological and social consequences of ipilimumab treatment in advanced melanoma A.H. Boekhout 1 , M. Hauptmann 2 , A.J.M. van den Eertwegh 3 , G.A.P. Hospers 4 , J.W.B. de Groot 5 , M.J.B. Aarts 6 , E. Kapiteijn 7 , A.J. Ten Tije 8 , D. Piersma 9 , W.H.J. Kruit 10 , K.P.M. Suijkerbuijk 11 , F.W.P.J. Berkmortel 12 , G. Vreugdenhil 13 , R. H. Koornstra 14 , E. Fiets 15 , M. Lees 16 , K.J.M. Janssen 17 , L.V. van den Poll-Franse 1 , C.U. Blank 18 1 Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, Netherlands, 2 Epidemiology, Netherlands Cancer Institute, Amsterdam, Netherlands, 3 Medical Oncology, VU University Medical Centre, Amsterdam, Netherlands, 4 Medical Oncology, University Medical Centre Groningen, Groningen, Netherlands, 5 Medical Oncology, Isala, Zwolle, Netherlands, 6 Medical Oncology, Maastricht University Medical Centre, Maastricht, Netherlands, 7 Medical Oncology, Leiden University Medical Centre, Leiden, Netherlands, 8 Medical Oncology, Amphia hospital, Breda, Netherlands, 9 Medical Oncology, Medical Spectrum Twente, Enschede, Netherlands, 10 Medical Oncology, Erasmus University Medical Centre, Rotterdam, Netherlands, 11 Medical Oncology, University Medical Centre Utrecht, Utrecht, Netherlands, 12 Medical Oncology, Atrium Medical Centre, Sittard, Netherlands, 13 Medical Oncology, Maxima Medical Centre, Eindhoven, Netherlands, 14 Medical Oncology, Radboud Medical Centre, Nijmegen, Netherlands, 15 Medical Oncology, Medical Centre Leeuwarden, Leeuwarden, Netherlands, 16 Oncology, Bristol-Meyers Squibb, Paris, France, 17 Oncology, Bristol- Meyers Squibb, Utrecht, Netherlands, 18 Medical Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands Background: After the introduction of ipilimumab, an anti-CTLA-4 monoclonal anti- body, durable, long term survival has become a possibility for a subgroup of advanced melanoma patients. Since ipilimumab is a relatively novel drug there are limited data on the long-term physical, psychological, and social functioning of these patients. This study will evaluate the long-term physical and psychosocial performances and the Annals of Oncology abstracts Volume 28 | Supplement 5 | September 2017 doi:10.1093/annonc/mdx377 | 447 Downloaded from https://academic.oup.com/annonc/article-abstract/28/suppl_5/mdx377.045/4109332 by guest on 30 July 2018