410TiP - Phase 2, open-label study of ceritinib in patients (pts) with advanced non-lung solid tumors and hematological malignancies characterized by geneti...

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Anti-Cancer Agents & Biologic Therapy
Presenter Igor Kiss
Citation Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368
Authors I. Kiss1, J. Rodon2, E. Grande Pulido3, S.Y. Rha4, S. Sathornsumetee5, G. Hess6, E. Eigendorff7, D. Cesic8, S. Sutradhar8, B. Pramanik8, T.M. Kim9
  • 1Clinic Of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, 65653 - Brno/CZ
  • 2Medical Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 3Medical Oncology, Hospital Universitario Ramon y Cajal, 28031 - Madrid/ES
  • 4Medical Oncology, Internal Medicine, Yonsei Severance Hospital Cancer Center, (120-752) - Seoul/KR
  • 5Faculty Of Medicine, Siriraj Hospital, Mahidol University, 10700 - Bangkok/TH
  • 6Department Of Hematology, Oncology And Pneumology, University Medical School of the Johannes Gutenberg-University, 55131 - Mainz/DE
  • 7Medical Oncology, Friedrich Schiller Univerisitaet, 07743 - Jena/DE
  • 8Oncology, Novartis Pharmaceuticals Corporation, 07936-1080 - East Hanover/US
  • 9Internal Medicine, Seoul National University Hospital, 110-744 - Seoul/KR

Abstract

Background

Genetic alterations in ALK are found in subsets of several cancers. In vitro and in vivo experiments have shown that neuroblastoma, anaplastic large cell lymphoma (ALCL) and non-small cell lung cancer (NSCLC) models carrying ALK alterations are sensitive to ALK inhibitors. In the ASCEND-1 study, pts with ALK+ ALCL (n=3) showed a dramatic response to ceritinib (Richly H et al, Blood 2015). Ceritinib also demonstrated antitumor activity in pediatric pts with ALK+ inflammatory myofibroblastic tumor (IMT) and ALCL (NCT01742286). These data provide a rationale to assess ceritinib in diverse ALK+ tumors other than NSCLC.

Trial design

ASCEND-10 is a prospective, open-label, multicenter, multi-arm study (NCT02465528) designed primarily to evaluate activity based on disease control rate (DCR) at 16 weeks by investigator in pts with advanced ALK+ non-lung solid tumors and ALK+ hematologic malignancies. Key secondary objectives: investigator-assessed ORR, DOR, time to response and overall safety. This trial will enroll adult pts with locally tested ALK gene aberrations. Eligible pts must have received ≥1 line of prior systemic treatment, provide an archival or fresh tissue prior to first dose. Other key inclusion criteria: presence of ≥1 measurable lesion defined by RECIST 1.1, and WHO PS ≤2. There will be ≥4 different tumor types (TT) in parallel arms: ALCL, IMT, glioblastoma, inflammatory breast cancer and any other non-lung ALK+ tumor. An adaptive design using a Bayesian Hierarchical model (BHM) will be used for the analysis of DCR. Proposed design is adaptive in the sense that it borrows information from other TT if efficacy is similar and provide more precise estimate of DCR. Early termination of a specific TT due to lack of efficacy is permitted. This flexible design also allows separate interim and final analysis for each TT once accrual and follow-up are complete for a given TT. Due to adaptive nature of the design the final sample size is not fixed. Approximately 106 pts are planned to be enrolled in this study.

Clinical trial identification

NCT01742286

Legal entity responsible for the study

Novartis Pharmaceutical Corporation

Funding

Novartis Pharmaceutical Corporation

Disclosure

I. Kiss: Has received speakers' honoraria from Roche, Merck, and Amgen. J. Rodón: Consulting/advisory: Novartis, Eli Lilly, Servier, Orion. G. Hess: Consulting/advisory:Janssen, Novartis, Pfizer, Roche, Celgene Research funding fees: Pfizer, Roche, CTI. D. Cesic, S. Sutradhar, B. Pramanik: Employee: Novartis. All other authors have declared no conflicts of interest.