PMID- 32486385
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 6
DP  - 2020 May 31
TI  - 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.
LID - 10.3390/cancers12061425 [doi]
LID - 1425
AB  - 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/m(2)/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.
FAU - de Braud, Filippo
AU  - de Braud F
AD  - Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Oncology Department, 
      University of Milan, via G. Venezian, 1, 20133 Milan, Italy.
FAU - Machiels, Jean-Pascal H
AU  - Machiels JH
AUID- ORCID: 0000-0001-6369-9742
AD  - Institut Roi Albert II, Service d'Oncologie Medicale, Cliniques Universitaires 
      Saint-Luc and Institut de Recherche Clinique et Experimentale (Pole MIRO), 
      Universite Catholique de Louvain, Avenue Hippocrate 10, 200 Woluwe-Saint-Lambert, 
      1200 Brussels, Belgium.
FAU - Boggiani, Daniela
AU  - Boggiani D
AD  - Medical Oncology Unit, University Hospital of Parma, Via Antonio Gramsci 14, 
      43126 Parma, Italy.
FAU - Rottey, Sylvie W H
AU  - Rottey SWH
AD  - Drug Research Unit Ghent, Ghent University Hospital, Corneel Heymanslaan 10, 9000 
      Ghent, Belgium.
FAU - Duca, Matteo
AU  - Duca M
AD  - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, via 
      G. Venezian, 1, 20133 Milan, Italy.
FAU - Laruelle, Marie
AU  - Laruelle M
AUID- ORCID: 0000-0002-0907-5805
AD  - Institut Roi Albert II, Cliniques Universitaires Saint-Luc and Institut de 
      Recherche Clinique et Experimentale (Pole MIRO), Universite catholique de 
      Louvain, Avenue Hippocrate 10, 200 Woluwe-Saint-Lambert, 1200 Brussels, Belgium.
FAU - Salvagni, Stefania
AU  - Salvagni S
AD  - Policlinico S. Orsola Malphigi, via Giuseppe Massarenti, 13, 40138 Bologna, 
      Italy.
FAU - Damian, Silvia
AU  - Damian S
AD  - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, via 
      G. Venezian, 1, 20133 Milan, Italy.
FAU - Lapeire, Lore D F
AU  - Lapeire LDF
AUID- ORCID: 0000-0002-5028-6305
AD  - Drug Research Unit Ghent, Ghent University Hospital, Corneel Heymanslaan 10, 9000 
      Ghent, Belgium.
FAU - Tiseo, Marcello
AU  - Tiseo M
AUID- ORCID: 0000-0002-9553-8465
AD  - Medical Oncology Unit, University Hospital of Parma, Via Antonio Gramsci 14, 
      43126 Parma, Italy.
FAU - Dermine, Alexandre
AU  - Dermine A
AD  - Institut Roi Albert II, Cliniques Universitaires Saint-Luc and Institut de 
      Recherche Clinique et Experimentale (Pole MIRO), Universite catholique de 
      Louvain, Avenue Hippocrate 10, 200 Woluwe-Saint-Lambert, 1200 Brussels, Belgium.
FAU - Ould-Kaci, Mahmoud
AU  - Ould-Kaci M
AD  - Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Rd, Ridgefield, CT 
      06877, USA.
FAU - Braunger, Juergen
AU  - Braunger J
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397 Biberach 
      an der Riss, Germany.
FAU - Rascher, Juliane
AU  - Rascher J
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397 Biberach 
      an der Riss, Germany.
FAU - Fischer, Daniela
AU  - Fischer D
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397 Biberach 
      an der Riss, Germany.
FAU - Hoefler, Josef
AU  - Hoefler J
AD  - Staburo GmbH, Aschauer Str. 26b, 81549 Munich, Germany, on behalf of Boehringer 
      Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
FAU - Mariani, Gabriella L
AU  - Mariani GL
AD  - Boehringer Ingelheim, via Giovanni Lorenzini, 8, 20139 Milan, Italy.
FAU - Cresta, Sara
AU  - Cresta S
AUID- ORCID: 0000-0002-6830-0662
AD  - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, via 
      G. Venezian, 1, 20133 Milan, Italy.
LA  - eng
GR  - N/A/Boehringer Ingelheim/
PT  - Journal Article
DEP - 20200531
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7352719
OTO - NOTNLM
OT  - BI 860585
OT  - clinical trial
OT  - mTOR serine-threonine kinases
OT  - maximum tolerated dose
OT  - pharmacokinetics
OT  - phase 1
COIS- Filippo de Braud reports membership of an advisory board or committee for 
      TizianaLife Sciences, BMS, Celgene, Novartis, Servier, Pharm Research Associated, 
      Daiichi Sankyo, Ignyta, Amgen, Pfizer, Octimet Oncology, Incyte, Teofarma, Pierre 
      Fabre, Roche, and EMD Serono; and consultancy for or receipt of speaker fees from 
      BMS, Eli Lilly, Roche, Amgen, AstraZeneca, Gentili, Fondazione Menarini, 
      Novartis, MSD, Ignyta, Bayer, Noema S.r.l., ACCMED, Dephaforum S.r.l., Nadirex, 
      Roche, Biotechspert Ltd., PriME Oncology, and Pfizer. Jean-Pascal H. Machiels 
      reports membership of an advisory board or committee for Pfizer, Roche, 
      AstraZeneca, Bayer, Innate, Merck Serono, Boehringer Ingelheim, BMS, Novartis, 
      Janssen, Incyte, Cue Biopharma, ALX Oncology, MSD, Debio, and Nanobiotix (managed 
      by institution); receipt of travel grants from Amgen, BMS, Pfizer, and MSD; and 
      receipt of a grant and a refund for work performed during the trial from 
      Boehringer Ingelheim. Marcello Tiseo reports membership of an advisory board or 
      committee for Boehringer Ingelheim; consultancy for/receipt of speaker fees from 
      Boehringer Ingelheim; research grants from AstraZeneca, and Boehringer Ingelheim; 
      receipt of advisory board and/or speaker fees from AstraZeneca, BMS, MSD, 
      Boehringer Ingelheim, and Takeda. Mahmoud Ould-Kaci, Juergen Braunger, and 
      Daniela Fischer report employment by Boehringer Ingelheim. Juliane Rascher 
      reports prior employment by Boehringer Ingelheim, and current employment by 
      SocraMetrics GmbH. Josef Hoefler reports membership of Staburo GmbH board of 
      directors; consultancy for/receipt of speaker fees from Boehringer Ingelheim, and 
      receipt of other financial support from Boehringer Ingelheim. Gabriella L. 
      Mariani reports prior employment by Boehringer Ingelheim, and current employment 
      by AstraZeneca. Daniela Boggiani, Sylvie W.H. Rottey, Matteo Duca, Marie 
      Laruelle, Stefania Salvagni, Silvia Damian, Lore D.F. Lapeire, Alexandre Dermine, 
      and Sara Cresta report no conflicts of interest.
EDAT- 2020/06/04 06:00
MHDA- 2020/06/04 06:01
PMCR- 2020/05/31
CRDT- 2020/06/04 06:00
PHST- 2020/03/23 00:00 [received]
PHST- 2020/05/04 00:00 [revised]
PHST- 2020/05/16 00:00 [accepted]
PHST- 2020/06/04 06:00 [entrez]
PHST- 2020/06/04 06:00 [pubmed]
PHST- 2020/06/04 06:01 [medline]
PHST- 2020/05/31 00:00 [pmc-release]
AID - cancers12061425 [pii]
AID - cancers-12-01425 [pii]
AID - 10.3390/cancers12061425 [doi]
PST - epublish
SO  - Cancers (Basel). 2020 May 31;12(6):1425. doi: 10.3390/cancers12061425.