Abstract 537P
Background
LY2880070 (LY) is an oral, selective competitive inhibitor of checkpoint kinase 1 (Chk1). LY and low-dose gemcitabine (LD GEM) was tolerable in advanced cancers. This combination has been assessed in advanced or metastatic high-grade serous ovarian cancer (HGSOC).
Methods
This two-part, open-label, multi-center study explored the safety, pharmacokinetics (PK), and anti-tumor activity of LY in patients with advanced or metastatic cancers. An expansion cohort was conducted in 27 patients with HGSOC. The primary objective of this Phase 2a cohort was to: 1) Characterize the dose-limiting toxicities (DLTs) and overall safety profile for LY+LD GEM in HGSOC; and 2) Evaluate the anti-tumor activity of LY + LD Gem. Patients received LY (50 mg b.i.d. X 5 days/week) + LD GEM (100 mg/m2) on days 1, 8, and 15 (optional) of a 21-day cycle.
Results
The combination of LY with GEM was generally well tolerated. The most common related adverse events included fatigue nausea, vomiting, diarrhea, fever, dyspnea, neutropenia, and thrombocytopenia. Treatment-emergent adverse events in >40% of ovarian patients included vomiting, nausea, anemia, fever, decreased appetite, ALT increased, abdominal pain, and fatigue. DLTs included reduced platelet count (Gr2), fatigue (Gr3), diarrhea (Gr3), and thrombocytopenia (x2, Gr2). Two patients (7.4%) had partial response (PR). Fourteen patients (51.9%) had stable disease, one of whom had an unconfirmed PR. Eleven patients (40.7%) achieved disease control ≥ 12 weeks.
Conclusions
This combination was generally tolerated in advanced or metastatic HGSOC. Further investigation is needed to better define biomarkers predictive of response in this patient population.
Clinical trial identification
NCT02632448.
Editorial acknowledgement
Legal entity responsible for the study
Esperas Pharma Inc.
Funding
Esperas Pharma Inc.
Disclosure
W.H. Miller: Financial Interests, Personal, Other, Consultant fees: Merck, BMS, Roche, GSK, Novartis, Amgen, Mylan, EMD Serono, Sanofi; Financial Interests, Personal, Other, Honoraria/speaker's bureau: BMS, Merck; Financial Interests, Personal, Other, Honoraria/Speaker’s Bureau: Roche, GSK, Novartis, Amgen, Mylan, EMD Serono, Sanofi; Financial Interests, Institutional, Research Grant, Grant: Merck, CIHR, CRS, Terry Fox Research Institute, SWCRF, CCSRI; Financial Interests, Institutional, Other, Clinical Trial: Merck, MiMic, Astellas, BMS, Novartis, GSK, Incyte, Pfizer, Sanofi, Ocellaris Pharma, Alkermes, Genentech, Array, Exelixis, VelosBio, Esperas Pharma. A.F. Shields: Financial Interests, Institutional, Principal Investigator: Esperas Pharma Inc. D. Provencher: Financial Interests, Institutional, Principal Investigator: Esperas Pharma Inc, Ocellaris Pharma Inc. L. Gilbert: Financial Interests, Institutional, Principal Investigator: Esperas Pharma Inc. G. Shapiro: Financial Interests, Personal, Advisory Board: Pfizer, Eli Lilly, G1 Therapeutics, Roche, Merck KGaA/EMD-Serono, Sierra Oncology, Bicycle Therapeutics, Fusion Pharmaceuticals, Cybrexa Therapeutics, Astex, Almac, Ipsen, Bayer, Angiex, Daiichi Sankyo, Seattle Genetics, Boehringer Ingelheim, ImmunoMet, Asana, Artios, Atrin, Concarlo Holdings, Syros, Zentalis, CytomX Therapeutics, Blueprint Medicines; Financial Interests, Institutional, Invited Speaker: Exelixis, Cyteir, Clovis, Samumed, Abbvie, Incyte, AstraZeneca, Novartis, Amgen, Bristol Myers Squibb, CanBas, Cyclacel, Aileron, PUMA; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer, Esperas, Bayer, Lilly, Boehringer Ingelheim, Seattle Genetics, Syros; Other, Other, Patent: Dosage regimen for sapacitabine and seliciclib, issued to Geoffrey Shapiro and Cyclacel Pharmaceuticals: Cyclacel; Other, Pending patent: Compositions and Methods for Predicting Response and Resistance to CDK4/6 Inhibition, with Liam Cornell, PhD (Dana-Farber Cancer Institute): Dana-Farber Cancer Institute. A.M. Oza: Financial Interests, Institutional, Principal Investigator: Esperas Pharma, Ocellaris Pharma Inc. J. Spratlin: Financial Interests, Institutional, Principal Investigator: AstraZeneca, Taiho, Celgene, Incyte, Amgen, BMS. S. Lheureux: Financial Interests, Institutional, Principal Investigator: Esperas Pharma Inc. G. Bhat: Financial Interests, Institutional, Principal Investigator: Esperas Pharma. S. Salvador: Financial Interests, Institutional, Principal Investigator: Esperas Pharma. P. Nunes: Financial Interests, Institutional, Principal Investigator: Esperas Pharma. S. Lau: Financial Interests, Institutional, Principal Investigator: Esperas Pharma. I. Weiner: Financial Interests, Institutional, Project Lead: Esperas Pharma. J. Keene: Financial Interests, Institutional, Principal Investigator: Esperas Pharma. S. Zaknoen: Financial Interests, Personal, Advisory Role: Esperas Pharma, Ocellaris Pharma, Medikine, Atara, Mirati. P. Smith: Financial Interests, Personal, Other, Employee: Eli Lilly. J. Stille: Financial Interests, Personal, Other, Employee: Eli Lilly. D. Vincett: Financial Interests, Personal, Other, Employee: Ozmosis Research. Q.S. Chu: Financial Interests, Institutional, Principal Investigator: Alkermes, Bicycle, Exactis, GSK, Mirati, Ocellaris Pharma, Revolution Medicine, Treadwell, TP Therapeutics; Financial Interests, Personal and Institutional, Principal Investigator, Advisory Board: Amgen, Astellas, Astra Zenec, BMS, Boehringer Ingelheim, Eli Lilly, Esperas Pharma, Merck, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Abbvie, AnHeart, Eisai, J&J, Jazz, Roche, Sanofi, Takeda.