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Open AccessArticle

A Phase 1 Study of mTORC1/2 Inhibitor BI 860585 as a Single Agent or with Exemestane or Paclitaxel in Patients with Advanced Solid Tumors

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Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Oncology Department, University of Milan, via G. Venezian, 1, 20133 Milan, Italy
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Institut Roi Albert II, Service d’Oncologie Médicale, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, Avenue Hippocrate 10, 200 Woluwe-Saint-Lambert, 1200 Brussels, Belgium
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Medical Oncology Unit, University Hospital of Parma, Via Antonio Gramsci 14, 43126 Parma, Italy
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Drug Research Unit Ghent, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium
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Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, via G. Venezian, 1, 20133 Milan, Italy
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Institut Roi Albert II, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université catholique de Louvain, Avenue Hippocrate 10, 200 Woluwe-Saint-Lambert, 1200 Brussels, Belgium
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Policlinico S. Orsola Malphigi, via Giuseppe Massarenti, 13, 40138 Bologna, Italy
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Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Rd, Ridgefield, CT 06877, USA
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Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397 Biberach an der Riß, Germany
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Staburo GmbH, Aschauer Str. 26b, 81549 Munich, Germany, on behalf of Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
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Boehringer Ingelheim, via Giovanni Lorenzini, 8, 20139 Milan, Italy
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Author to whom correspondence should be addressed.
Current address: SocraMetrics GmbH, Mainzerhofpl. 14, 99084 Erfurt, Germany.
Current address: AstraZeneca, Granta Park, Great Abington, Cambridge CB21 6GP, UK.
Cancers 2020, 12(6), 1425; https://doi.org/10.3390/cancers12061425
Received: 23 March 2020 / Revised: 4 May 2020 / Accepted: 16 May 2020 / Published: 31 May 2020
This phase 1 trial (NCT01938846) determined the maximum tolerated dose (MTD) of the mTOR serine/threonine kinase inhibitor, BI 860585, as monotherapy and with exemestane or paclitaxel in patients with advanced solid tumors. This 3+3 dose-escalation study assessed BI 860585 monotherapy (5–300 mg/day; Arm A), BI 860585 (40–220 mg/day; Arm B) with 25 mg/day exemestane, and BI 860585 (80–220 mg/day; Arm C) with 60–80 mg/m2/week paclitaxel, in 28-day cycles. Primary endpoints were the number of patients with dose-limiting toxicities (DLTs) in cycle 1 and the MTD. Forty-one, 25, and 24 patients were treated (Arms A, B, and C). DLTs were observed in four (rash (n = 2), elevated alanine aminotransferase/aspartate aminotransferase, diarrhea), four (rash (n = 3), stomatitis, and increased gamma-glutamyl transferase), and two (diarrhea, increased blood creatine phosphokinase) patients in cycle 1. The BI 860585 MTD was 220 mg/day (Arm A) and 160 mg/day (Arms B and C). Nine patients achieved an objective response (Arm B: Four partial responses (PRs); Arm C: Four PRs; one complete response). The disease control rate was 20%, 28%, and 58% (Arms A, B, and C). The most frequent treatment-related adverse events (AEs) were hyperglycemia (54%) and diarrhea (39%) (Arm A); diarrhea (40%) and stomatitis (40%) (Arm B); fatigue (58%) and diarrhea (58%) (Arm C). The MTD was determined in all arms. Antitumor activity was observed with BI 860585 monotherapy and in combination with exemestane or paclitaxel. View Full-Text
Keywords: mTOR serine-threonine kinases; BI 860585; clinical trial; phase 1; maximum tolerated dose; pharmacokinetics mTOR serine-threonine kinases; BI 860585; clinical trial; phase 1; maximum tolerated dose; pharmacokinetics
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de Braud, F.; Machiels, J.-P.H.; Boggiani, D.; Rottey, S.W.; Duca, M.; Laruelle, M.; Salvagni, S.; Damian, S.; Lapeire, L.D.; Tiseo, M.; Dermine, A.; Ould-Kaci, M.; Braunger, J.; Rascher, J.; Fischer, D.; Hoefler, J.; Mariani, G.L.; Cresta, S. A Phase 1 Study of mTORC1/2 Inhibitor BI 860585 as a Single Agent or with Exemestane or Paclitaxel in Patients with Advanced Solid Tumors. Cancers 2020, 12, 1425.

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