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.

Filippo de Braud, Jean-Pascal H. Machiels, Daniela Boggiani, Sylvie W. H. Rottey, Matteo Duca, Marie Laruelle, Stefania Salvagni, Silvia Damian, Lore D. F. Lapeire, Marcello Tiseo, Alexandre Dermine, Mahmoud Ould-Kaci, Juergen Braunger, Juliane Rascher, Daniela Fischer, Josef Hoefler, Gabriella L. Mariani, Sara Cresta

Research output: Contribution to journalArticlepeer-review

Abstract

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 58Arms 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.
Original languageEnglish
JournalCancers
Volume12
Issue number6
DOIs
Publication statusPublished - May 1 2020

Keywords

  • *clinical trial
  • *BI 860585
  • *maximum tolerated dose
  • *mTOR serine-threonine kinases
  • *pharmacokinetics
  • *phase 1

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