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Registrational dataset from the phase I/II ARROW trial of pralsetinib (BLU-667) in patients (pts) with advanced RET fusion+ non-small cell lung cancer (NSCLC).

Abstract

9515
Background: Pralsetinib is an investigational, highly potent, selective RET kinase inhibitor targeting oncogenic RET alterations. We provide the registrational dataset for pts with RET fusion+ NSCLC with and without prior treatment from the global ARROW study. Methods: ARROW (75 sites in 11 countries; NCT03037385) consists of a phase I dose escalation to establish recommended phase II dose (400 mg once daily [QD] orally) and phase II expansion cohorts defined by tumor type and/or RET alteration. Primary objectives were overall response rate (ORR; blinded independent central review per RECIST v1.1) and safety. Efficacy analyses are shown for response-evaluable pts (REP) with RET fusion+ NSCLC who initiated 400 mg QD pralsetinib by July 11 2019 and safety for all pts (regardless of diagnosis) treated with 400 mg QD. Results: As of November 18 2019, 354 pts with advanced solid tumors had received pralsetinib at starting dose of 400 mg QD with median follow-up 8.8 months. ORR, disease control rate (DCR), and % of pts with tumor size reduction are shown in the table for pts with metastatic RET fusion+ NSCLC (n=116; 72% KIF5B; 16% CCDC6; 12% other/fusion present but type unknown) and with prior platinum treatment (n=80) or without prior systemic treatment (n=26). ORR was similar regardless of RET fusion partner, prior therapies, or central nervous system involvement. Overall there were 7 (6%) complete responses, 4 (5%) in prior platinum pts and 3 (12%) in treatment naïve pts; median time to response overall was 1.8 months and median duration of response (DOR) was not reached (95% CI, 11.3–NR). In the safety population (n=354), most treatment-related adverse events (TRAEs) were grade 1-2, and included increased aspartate aminotransferase (31%), anemia (22%), increased alanine aminotransferase (21%), constipation (21%) and hypertension (20%). 4% of pts in the safety population (all tumor types) discontinued due to TRAEs. Conclusions: Updated, registrational, centrally reviewed data demonstrate that pralsetinib has rapid, potent, and durable clinical activity in pts with advanced RET fusion+ NSCLC regardless of RET fusion genotype or prior therapies, and QD oral dosing is well-tolerated. Clinical trial information: NCT03037385.
 Overall (n=116a)Prior platinum treatment (n=80)No prior systemic treatment (n=26)
ORR, % (95% CI)65 (55–73)b61 (50–72)b73 (52–88)
DCR, % (95% CI)93 (87–97)95 (88–99)88 (70–98)
Tumor size reduction, % of pts9695100
aIncluding n=10 with prior non-platinum treatment
bIncluding n=2 with partial response pending confirmation

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Journal of Clinical Oncology
Pages: 9515

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Published in print: May 20, 2020
Published online: May 25, 2020

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Justin F. Gainor
Massachusetts General Hospital, Boston, MA;
Giuseppe Curigliano
European Institute of Oncology, Milan, Italy;
Dong-Wan Kim
Seoul National University Hospital, Seoul, South Korea;
Dae Ho Lee
University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea;
Benjamin Besse
Gustave Roussy Université Paris Sud, Villejuif, France;
Christina S Baik
University of Washington School of Medicine, Main Hospital, Seattle, WA;
Robert C Doebele
University of Colorado Cancer Center, Aurora, CO;
Philippe Alexandre Cassier
Centre Léon Bérard, Lyon, France;
Gilberto Lopes
University of Miami Health System, Miami, FL;
Daniel Shao-Weng Tan
National Cancer Centre Singapore, Singapore, Singapore;
Elena Garralda
Hospital Universitari Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain;
Luis G. Paz-Ares
Hospital Universitario 12 de Octubre, Madrid, Spain;
Byoung Chul Cho
Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea;
Shirish M. Gadgeel
University of Michigan, Ann Arbor, MI;
Michael Thomas
Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany;
Stephen V. Liu
Georgetown University, Washington, DC;
Corinne Clifford
Blueprint Medicines Inc, Cambridge, MA;
Hui Zhang
Blueprint Medicines Inc, Cambridge, MA;
Christopher D. Turner
Blueprint Medicines Inc, Cambridge, MA;
Vivek Subbiah
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX;
Massachusetts General Hospital, Boston, MA; European Institute of Oncology, Milan, Italy; Seoul National University Hospital, Seoul, South Korea; University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea; Gustave Roussy Université Paris Sud, Villejuif, France; University of Washington School of Medicine, Main Hospital, Seattle, WA; University of Colorado Cancer Center, Aurora, CO; Centre Léon Bérard, Lyon, France; University of Miami Health System, Miami, FL; National Cancer Centre Singapore, Singapore, Singapore; Hospital Universitari Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; Hospital Universitario 12 de Octubre, Madrid, Spain; Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea; University of Michigan, Ann Arbor, MI; Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany; Georgetown University, Washington, DC; Blueprint Medicines Inc, Cambridge, MA; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX

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Blueprint Medicines Inc

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Justin F. Gainor, Giuseppe Curigliano, Dong-Wan Kim, Dae Ho Lee, Benjamin Besse, Christina S Baik, Robert C Doebele, Philippe Alexandre Cassier, Gilberto Lopes, Daniel Shao-Weng Tan, Elena Garralda, Luis G. Paz-Ares, Byoung Chul Cho, Shirish M. Gadgeel, Michael Thomas, Stephen V. Liu, Corinne Clifford, Hui Zhang, Christopher D. Turner, Vivek Subbiah
Journal of Clinical Oncology 2020 38:15_suppl, 9515-9515

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