90O Dose optimization of zovegalisib, a novel PI3Kα inhibitor, in patients (pts) with PIK3CA-mutant (m) HR+/HER2− advanced breast cancer (BC): Results from the first-in-human (FIH) study to support the recommended phase III dose

ESMO Open 2026 Open access

Read full text
Authors: A. Varkaris, A. Italiano, S. Sammons, E. Felip Falgas, A.M. Schram, B. Pistilli, A. Schott, P. Tolosa Ortega, K. Wisinski, M. Wei, R. Nanda, J. E. McGuinness
+8 more J. Rodon Ahnert, S. Ehsani, J.J. Liu, A. Timm, J. Shen, E.L. Kwak, Cristina Saura Manich, G. Curigliano
DOI: 10.1016/j.esmoop.2026.106232
Cited by: 1

Abstract

Oncogenic PIK3CA mutations activate PI3Kα in ∼40% of HR+/HER2- BC and define a validated therapeutic target. Approved PI3K inhibitors target the orthosteric site shared by mutant and WT PI3Kα, causing WT-associated toxicities such as hyperglycemia, rash, diarrhea, and stomatitis. Zovegalisib (zovega, RLY-2608) is an allosteric pan-mutant selective inhibitor that targets mutant forms of PI3Kα while sparing WT. The ReDiscover FIH trial studied zovega with standard-dose fulvestrant (F) in CDK4/6 inhibitor (i)-experienced pts with PIK3CAm HR+/HER2- ABC and defined 600 mg BID fasted as the recommended phase 2 dose (RP2D).

Fields of Study & Subjects

PI3K/AKT/mTOR signaling in cancer Advanced Breast Cancer Therapies HER2/EGFR in Cancer Research

Publication details

Journal / source
ESMO Open
Publisher
Elsevier BV
Volume
11
Pages
106232–106232
Publication date
1 April 2026
Language
EN