Phase II study of ipilimumab in adolescents with unresectable stage III or IV malignant melanoma
Institution:
1. Gustave Roussy, Université Paris-Saclay, Department of Pediatric and Adolescent Oncology, Villejuif, France;2. Institut D''Hematologie et D''Oncologie Pédiatrique, Centre Léon Bérard, Lyon, France;3. University of Colorado School of Medicine, Children''s Hospital Colorado, Aurora, CO, USA;4. University of California, Irvine School of Medicine, Orange, CA, USA;5. Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA;6. University of Texas, MD Anderson Cancer Center, Houston, TX, USA;7. Ghent University Hospital, Ghent, Belgium;8. Hospital Sant Joan de Déu Barcelona, Barcelona, Spain;9. Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;10. Bristol-Myers Squibb, Princeton, NJ, USA;11. St. Jude Children''s Research Hospital, Memphis, TN, USA;1. Uropediatric Unit, Division of Urology, Hospital da Clínicas, University of São Paulo Medical School, São Paulo, Brazil;2. Department of Pediatrics, Instituto da Criança, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, Brazil;1. Department of Pediatric Neurology, Warsaw Medical University, Warsaw, Poland;2. Department of Neurology and Epileptology, The Children''s Memorial Health Institute, Warsaw, Poland;3. Department of Oncology, Novartis Pharmaceuticals Corporation, Florham Park, NJ;4. Department of Oncology, Novartis Pharmaceuticals S.A.S., Rueil-Malmaison, France;5. Department of Neurology, Cincinnati Children''s Hospital Medical Center, Cincinnati, OH;1. Department of Pediatric Oncology, University Children''s Hospital, Zurich, Switzerland;2. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;3. Department of Pediatric Oncology, University of Wuerzburg, Wuerzburg, Germany;4. Institute of Biostatistics and Clinical Research, University of Muenster, Germany;6. Department of Radiation Oncology, Medical Faculty, Heinrich Heine University of Duesseldorf, Duesseldorf, Germany;5. Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;7. Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria;11. Department of Neuropathology, University of Bonn, Bonn, Germany;12. Department of Neuroradiology, University of Wuerzburg, Wuerzburg, Germany;8. Department of Radiation Oncology, University of Leipzig, Leipzig, Germany;1. Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China;2. Department of Hematology, Liaocheng People’s Hospital, Liaocheng, Shandong 252000, PR China;3. Haisheng Oncology Hospital of Qingdao, Qingdao, Shandong 266031, PR China;4. School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia;1. Institut d''Hématologie et d''Oncologie pédiatrique, Place Professeur Joseph Renaut, 69008 Lyon, France;2. Department of Oncology, MS 260, Room C6067, St. Jude Children''s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA;3. The Institute of Cancer Research, The Royal Marsden Hospital, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK;4. Department of Pediatrics, University of Colorado School of Medicine, 13001 East 17th Place, Aurora, CO 80045, USA;5. Childrens Hospital of Colorado, 13123 East 16th Avenue, B115, Aurora, CO 80045-7106, USA;6. Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA;7. Department of Pediatric Oncology, Institut Curie, 26, rue d''Ulm, 75248 Paris cedex 05, France;8. Clinical Research, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA;9. Quantitative Solutions B.V., Pivot Park Molenweg 79, 5349 AC Oss, The Netherlands;10. BARDS, MSD R&D (China) Co. Ltd., Universal Business Park, No. 10 Jiu Xianqiao Road, Chao Yang District, Beijing 100015, China;11. Department of Pediatric and Adolescent Oncology, Gustave Roussy, Univ. Paris-Sud, 114, rue Edouard Vaillant, 94805 Villejuif, France
Abstract:
BackgroundIpilimumab is approved for the treatment of advanced melanoma in adults; however, little information on the efficacy and safety of ipilimumab in younger patients is available.MethodsPatients aged 12 to <18 years with previously treated or untreated, unresectable stage III or IV malignant melanoma received ipilimumab 3 or 10 mg/kg every 3 weeks. Primary end-points were 1-year overall survival and safety.ResultsOver a period of 3.5 years, 12 patients received ipilimumab at either 3 mg/kg (n = 4) or 10 mg/kg (n = 8). The median number of ipilimumab doses was four for 3 mg/kg and three for 10 mg/kg. At 1 year, three of four patients on 3 mg/kg and five of eight patients on 10 mg/kg were alive. Two patients on 10 mg/kg had partial response, and one on 3 mg/kg had stable disease. One patient had durable partial response at 3 years without further treatment, at time of this report. There was one grade 3/4 immune-mediated adverse reaction with 3 mg/kg and five with 10 mg/kg. There were no treatment-related deaths. The study was stopped due to slow accrual.ConclusionsAt >1 year follow-up, ipilimumab demonstrated activity in melanoma patients aged 12 to <18 years, with a similar safety profile as that seen in adults. Our trial highlights the difficulties of enrolling younger patients with rare diseases in clinical trials for treatments that are approved in adults, suggesting adolescents with cancer types occurring predominantly in adults should be considered for inclusion in adult trials of promising new drugs.Clinical trial registration: NCT01696045.
