Phase 1 cohort expansion study of LY3023414, a dual PI3K/mTOR inhibitor, in patients with advanced mesothelioma

• DOI: 10.1007/s10637-021-01086-6
• Publication Date: 2021-03-04T04:42:05Z
• Authors: Marjorie G. Zauderer; Evan W. Alley; Johanna Bendell; Enrica Capelletto; Todd M. Bauer; Sophie Callies; Anna M. Szpurka; Suhyun Kang; Melinda D. Willard; Volker Wacheck; Anna M. Varghese
• Keywords: Tolerability

Summary BACKGROUND LY3023414 is a selective, ATP competitive inhibitor of class I PI3K isoforms, mTORC1/2 and DNA-PK. A Phase 1 dose escalation, 200 mg twice daily (BID) was the determined recommended phase 2 (RP2D). We report antitumor activity safety monotherapy in patients with advanced mesothelioma. METHODS Patients enrolled had malignant pleural or peritoneal mesothelioma measurable disease, ECOG PS 0–1, were refractory ineligible to receive standard therapies. received BID. This expansion cohort intended evaluate preliminary by overall response rate. Safety, tolerability pharmacokinetics assessed. Biomarkers associated treatment an exploratory endpoint. RESULTS Forty-two for median duration 11.2 weeks (range: 1.1–53.0). One patient confirmed partial (PR) (ORR 2.4%). Three unconfirmed PR. Seventeen stable disease (SD) (DCR 43%). Most common adverse events (AEs) included fatigue (43%), nausea decreased appetite (38%), vomiting (33%), diarrhea (29%). AEs mostly mild moderate. Grade ≥ 3 reported 21% as most frequent event (10%). Alterations BAP1 identified 11/19 molecular aberration, followed SETD2 NF2 alterations. No obvious pattern genetic changes/mutations single genes pathways anti-tumor activity. CONCLUSION (200 BID) demonstrated acceptable manageable profile limited single-agent ClinicalTrials.gov identifier: NCT01655225; Date registration: 19 July 2012.