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AACR 2022 | Investigating the ATR inhibitor elimusertib in advanced solid tumors

Timothy Yap, MBBS, PhD, MRCP, PgDip, University of Texas MD Anderson Cancer Center, Houston, TX, explains the Phase Ib expansion trial (NCT03188965) assessing the safety and efficacy of the ataxia telangiectasia and Rad3-related (ATR) inhibitor elimusertib in patients with advanced solid tumors carrying DNA damage response (DDR) defects. ATR inhibitors prevent DNA damage checkpoint activation and disrupt DDR by binding to ATR and blocking ATR mediator signalling. 143 patients with advanced solid tumors with different putative deleterious DDR alterations participated in the trial. Clinical benefit with disease control for at least 16 weeks was achieved in approximately 35% of patients and overall durable objective responses were seen across a variety of cancer types. Importantly, 27.8% of patients with advanced ovarian cancer, including those resistant to platinum-based therapy and those who had previously received PARP inhibitor therapy, experienced durable clinical benefit that lasted longer than 6 months. Furthermore, 26.5% of patients with ATM loss had durable clinical benefit lasting more than 6 months. Going forward, we need to better identify molecular biomarkers that can predict which patients are most likely to benefit from elimusertib monotherapy. Rational combination strategies are currently investigating elimusertib with the PARP inhibitor niraparib and the PD-1 inhibitor pembrolizumab. This interview took place at the American Association for Cancer Research Annual Meeting in New Orleans, LA.


Employment: University of Texas MD Anderson Cancer Center, where I am Medical Director of the Institute for Applied Cancer Science, which has a commercial interest in DDR and other inhibitors (IACS30380/ART0380 was licensed to Artios)

Grant/Research support (to Institution): Acrivon, Artios, AstraZeneca, Bayer, Beigene, BioNTech, Blueprint, BMS, Clovis, Constellation, Cyteir, Eli Lilly, EMD Serono, Forbius, F-Star, GlaxoSmithKline, Genentech, Haihe, ImmuneSensor, Ionis, Ipsen, Jounce, Karyopharm, KSQ, Kyowa, Merck, Mirati, Novartis, Pfizer, Ribon Therapeutics, Regeneron, Repare, Rubius, Sanofi, Scholar Rock, Seattle Genetics, Tesaro, Vivace and Zenith.

Consultancies: AbbVie, AstraZeneca, Acrivon, Adagene, Almac, Aduro, Amphista, Artios, Athena, Atrin, Avoro, Axiom, Baptist Health Systems, Bayer, Beigene, Boxer, Bristol Myers Squibb, C4 Therapeutics, Calithera, Cancer Research UK, Clovis, Cybrexa, Diffusion, EMD Serono, F-Star, Genmab, Glenmark, GLG, Globe Life Sciences, GSK, Guidepoint, Idience, Ignyta, I-Mab, ImmuneSensor, Institut Gustave Roussy, Intellisphere, Jansen, Kyn, MEI pharma, Mereo, Merck, Natera, Nexys, Novocure, OHSU, OncoSec, Ono Pharma, Pegascy, PER, Pfizer, Piper-Sandler, Prolynx, Repare, resTORbio, Roche, Schrodinger, Theragnostics, Varian, Versant, Vibliome, Xinthera, Zai Labs and ZielBio

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