Poster Presentation Advances in Neuroblastoma Research Congress 2016

Phase I study of anti-GD2 antibody ch14.18/CHO long term infusion in recurrent or refractory neuroblastoma patients in Japan (#327)

Atsushi Narita 1 , Yoshiyuki Takahashi 1 , Nikolai Siebert 2 , Nobuhiro Nishio 1 , Xinan Wang 1 , Yinyan Xu 1 , Yusuke Okuno 1 , Daiei Kojima 1 , Kyogo Suzuki 1 , Norihiro Murakami 1 , Rieko Taniguchi 1 , Daisuke Ichikawa 1 , Motoharu Hamada 1 , Shinsuke kataoka 1 , Yuko Sekiya 1 , Nozomu Kawashima 1 , Eri Nishikawa 1 , Michi Kamei 1 , Hideki Muramatsu 1 , Asahito Hama 1 , Takehiko Kamijo 3 , Atsuko Nakazawa 4 , Hajime Hosoi 5 , Yoshiaki Kinoshita 6 , Shinobu Shimizu 7 , Katsuyoshi Kato 7 , Masaaki Mizuno 7 , Hans Loibner 8 , Tatsuro Tajiri 9 , Akira Nakagawara 9 , Ruth Ladenstein 10 , Holger N Lode 3 , Seiji Kojima 1
  1. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya
  2. Department of Pediatric Oncology and Hematology, University Medicine Greifswald, Greifswald
  3. Research Institute for Clinical Oncology, Saitama Cancer Center, Ina
  4. Department of Pathology, Tokai University School of Medicine, Isehara
  5. Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto
  6. Department of Pediatric Surgery, Kyushu University, Fukuoka
  7. Centre for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya
  8. Apeiron Biologics AG, CEO, Vienna
  9. Japan Neuroblastoma Study Group, Tokyo
  10. Paediatric Haematology/Oncology, St. Anna Children's Hospital and Research Institute for the SIOP Europe Neuroblastoma Group, Vienna

Background: The primary objective of this study was to assess safety and tolerability of single agent monoclonal anti-GD2 antibody ch14.18/CHO continuous long-term-infusion (LTI) in Japanese neuroblastoma patients. Secondary objectives were to evaluate pharmacokinetic (PK) and pharmacodynamics (PD) parameters and anti-tumor activity in patients with evaluable diseases.

Methods: Continuous infusion of 100 mg/m2/cycle (3.3mg/kg/cycle if body weight ≤12 kg) ch14.18/CHO was administered over 10 consecutive days every 5 weeks. Patients could receive up to five cycles. Blood samples were collected for assessment of PK, HACA response, immunophenotype, ADCC, CDC, biochemistry, Fc gamma receptor polymorphism, and MRD assessment.

Results: Ten patients with recurrent/refractory neuroblastoma were enrolled between September 2014 and July 2015. Nine patients (5 boys and 4 girls) were eligible and evaluable for toxicity and response assessments in this study. The median age was 4 (range 2-9) years old. Grade 3 or higher toxicities included anemia, leukopenia, neutropenia, elevation of hepatic transaminases, hyponatremia, and urticalia, but all these toxicities were reversible until the next scheduled cycle. The supportive care guidelines allowed all patients to continue the treatment at the same dose level. No unexpected Grade 4 toxicities were observed. PK parameters of ch14.18/CHO in Japanese patients were not different from Caucasian patients. All evaluable patients revealed an increased ADCC response over base line against neuroblastoma cells. Three of nine patients had partial responses evaluated by MIBG scans or tumor marker analysis. One patient discontinued after 2 cycles because of progressive disease in central nervous system. Eight patients are alive with stable disease without further chemotherapy (median follow-up 10 months from enrollment; range 7-17).

Conclusion: Japanese patients receiving ch14.18/CHO for high risk neuroblastoma had similar PK, tolerability and objective response rate compared to Caucasian patients. These results bridge data of ch14.18/CHO between Asian and Caucasian patients.