Abstract 1628TiP
Background
CIT is a common and challenging complication of cancer therapy, resulting in chemotherapy dose reduction, treatment delay, and discontinuation. Platelet (Plt) transfusions provide only a transient benefit, are costly, associated with risk of adverse events, and have limited availability. Until recently, chemotherapy dose modifications and Plt transfusions were the only management options for CIT. NCCN guidelines now include consideration of the TPO receptor agonist romiplostim for CIT based on data from a phase 2 prospective randomized study and retrospective studies. We describe here two ongoing pivotal phase 3 RCT of romiplostim to treat CIT.
Trial design
Adult patients receive (trial 1) oxaliplatin-based chemotherapy for gastrointestinal, pancreatic, or colorectal cancer (NCT03362177) or (trial 2) carboplatin-based chemotherapy for non-small cell lung, ovarian, or breast cancer (NCT03937154). In each trial, 162 patients with Plt ≤85×109/L and CIT from a prior regimen will be randomized 2:1 to receive romiplostim or placebo, respectively, stratified by baseline Plt count and tumor type (trial 1) or specific carboplatin regimen (trial 2). After initiation of study drug at 2 μg/kg subcutaneously, patients will be dosed weekly, adjusting by 1 μg/kg to ≤10 μg/kg, to achieve Plt counts ≥100×109/L. Chemotherapy can start when Plt counts are >100×109/L or Week 4 per investigator; after 12 weeks, those not achieving Plt counts ≥100×109/L, or a Plt count deemed safe to proceed with chemotherapy, stop treatment and enter follow-up. Interim analyses for each trial will occur when 81 patients have completed 3 chemotherapy cycles. The primary endpoint for both studies is thrombocytopenia-induced dose modification of any myelosuppressive agent in the second and third cycles of the planned chemotherapy regimen (ie, dose reduction, delay, omission, or discontinuation) as adjudicated by an independent committee (oncologists and a biostatistician). Secondary endpoints include depth of the Plt nadir, time to Plt response, duration-adjusted rate of grade ≥2 bleeding, overall survival, Plt transfusion incidence, proportion achieving a Plt response, and safety.
Clinical trial identification
NCT03362177, NCT03937154.
Editorial acknowledgement
Susanna Mac of Amgen Inc provided medical writing support.
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
H. Al-Samkari: Financial Interests, Personal, Advisory Role: Forma, Novartis, Rigel, Moderna, Argenx, Dova/Sobi, Agios; Financial Interests, Personal, Research Grant: Amgen, Dova/Sobi, Agios. C. Geredeli: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Roche, Amgen, Bayer, Pfizer, Takeda, Astellas, AstraZeneca, Merck, Eczacibasi, Novartis, Deva. C. Arslan: Financial Interests, Personal, Research Grant: Roche, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Nektar, Johnson & Johnson, Lilly, Amgen, Astellas, Teva, Bayer, Henlius, Yuhan, Daiichi Sankyo, Pfizer, Sanofi-Aventis, Incyte; Financial Interests, Personal, Advisory Role: Roche, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Johnson & Johnson, Lilly, Amgen, Astellas, Teva, Pfizer, Bayer; Financial Interests, Personal, Support for attending meetings and/or travel: Novartis, Bristol Myers Squibb, AstraZeneca, Johnson & Johnson, Amgen, Astellas, Teva, Pfizer, Bayer; Financial Interests, Personal, Advisory Board: Novartis, Bristol Myers Squibb, AstraZeneca, Johnson & Johnson, Amgen, Astellas, Teva, Pfizer, Bayer. M. Salgado Fernandez: Financial Interests, Personal, Advisory Role: Amgen, Celgene, Servier; Financial Interests, Personal, Speaker’s Bureau: Amgen, Bristol Myers Squibb, Merck Serono, Rovi; Financial Interests, Personal, Travel, Accommodations, Expenses: Merck, Roche, Sanofi. T. Ciuleanu: Financial Interests, Personal, Advisory Role: A&D Pharma, Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, Servier; Financial Interests, Personal, Travel, Accommodations, Expenses: A&D Pharma, Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Ipsen, Janssen, Lilly, Merck, MSD, Novartis, Pfizer, Roche/Genentech, Sanofi, Servier. C. Bowers: Financial Interests, Personal, Full or part-time Employment: Amgen Inc; Financial Interests, Personal, Stocks/Shares: Amgen Inc. A. Armas: Financial Interests, Personal, Full or part-time Employment: Amgen Inc; Financial Interests, Personal, Stocks/Shares: Amgen Inc. F. Scotté: Financial Interests, Personal, Advisory Role: Amgen, Mylan, Roche, Mundipharma, Leo Pharma, Tesaro, Helsinn, Tilray, Vifor Pharma, Pfizer, Pierre Fabre Oncology, Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Amgen, Roche. P.A. Bunn: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck, Genentech, Lilly, Bristol Myers Squibb, Takeda, CStone, Ascentage, Imidex; Financial Interests, Personal, Member of the Board of Directors: Verastem. D. Kuter: Financial Interests, Personal, Research Grant: Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, Bristol Myers Squibb, Immunovant, Kezar, Principia, Protalex, Rigel, Takeda (Bioverativ), UCB; Financial Interests, Personal, Advisory Role: Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, BioCryst, Bristol Myers Squibb, Caremark, CRICO, Daiichi Sankyo, Dova, Genzyme, Immunovant, Incyte, Kyowa Kirin, MSD, Momenta, Novartis, Pfizer, Platelet Disorder Support Association, Principia, Protalex, Rigel, Sanofi, Shionogi, Shire, Takeda (Bioverativ), UCB, Up-To-Date, Zafgen. G.A. Soff: Financial Interests, Personal, Research Grant: Amgen, Janssen Scientific Affairs, Dova Pharmaceuticals, Hengrui USA. All other authors have declared no conflicts of interest.