한빛사논문
- 조회267
David S. Hong 1,*, Michael Postow 2, Bartosz Chmielowski 3, Ryan Sullivan 4, Amita Patnaik 5, Ezra E.W. Cohen 6, Geoffrey Shapiro 7, Conor Steuer 8, Martin Gutierrez 9, Heather Yeckes-Rodin 10, Robert Ilaria Jr 11, Brenda O’Connell 11, Joanna Peng 11, Guangbin Peng 11, Nora Zizlsperger 11, Anthony Tolcher 12, and Jedd D. Wolchok 13
1MD Anderson Cancer Center, Houston, Texas.
2Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York.
3Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California.
4Massachusetts General Hospital, Boston, Massachusetts.
5South Texas Accelerated Research Therapeutics (START), San Antonio, Texas.
6Moores Cancer Center at UC San Diego Health, San Diego, California.
7DanaFarber Cancer Institute, Boston, Massachusetts.
8Winship Cancer Institute of Emory University, Emory University School of Medicine, Atlanta, Georgia.
9Regional Cancer Care Associates, Hackensack, New Jersey.
10Martin Medical Center, Port Saint Lucie, Florida.
11Infinity Pharmaceuticals, Inc., Cambridge, Massachusetts.
12NEXT Oncology, San Antonio, Texas.
13Weill Cornell Medicine, New York, New York.
D.S. Hong and M. Postow contributed equally as co-senior authors of this article
*Corresponding author: correspondence to David S. Hong
Abstract
Purpose: Eganelisib (IPI-549) is a first-in-class, orally administered, highly selective PI3Kγ inhibitor with antitumor activity alone and in combination with programmed cell death protein 1/ligand 1 (PD-1/PD-L1) inhibitors in preclinical studies. This phase 1/1b first-in-human, MAcrophage Reprogramming in Immuno-Oncology-1 (NCT02637531) study evaluated the safety and tolerability of once-daily eganelisib as monotherapy and in combination with nivolumab in patients with solid tumors.
Patients and methods: Dose-escalation cohorts received eganelisib 10-60 mg as monotherapy (n = 39) and 20-40 mg when combined with nivolumab (n = 180). Primary endpoints included incidence of dose-limiting toxicities (DLT) and adverse events (AE).
Results: The most common treatment-related grade ≥3 toxicities with monotherapy were increased alanine aminotransferase (ALT; 18%), aspartate aminotransferase (AST; 18%), and alkaline phosphatase (5%). No DLTs occurred in the first 28 days; however, toxicities meeting DLT criteria (mostly grade 3 reversible hepatic enzyme elevations) occurred with eganelisib 60 mg in later treatment cycles. In combination, the most common treatment-related grade ≥3 toxicities were increased AST (13%) and increased ALT and rash (10%). Treatment-related serious AEs occurred in 5% of monotherapy patients (grade 4 bilirubin and hepatic enzyme increases in one patient each) and 13% in combination (pyrexia, rash, cytokine release syndrome, and infusion-related reaction in ≥2 patients each). Antitumor activity was observed in combination, including patients who had progressed on PD-1/PD-L1 inhibitors.
Conclusions: On the basis of the observed safety profile, eganelisib doses of 30 and 40 mg once daily in combination with PD-1/PD-L1 inhibitors were chosen for phase 2 study.
논문정보
- Research article
- 2023년 06월 (BRIC 등록일 2023-08-22)
- 국외 연구진
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