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AACR 2022 | TRESR trial: Investigating an ATRi in patients with DNA damage repair loss-of-function mutant tumors

Timothy Yap, MBBS, PhD, MRCP, PgDip, University of Texas MD Anderson Cancer Center, Houston, TX, outlines updates from the Phase I/II TRESR trail (NCT04497116) which assessed RP-3500, a ataxia telangiectasia and Rad3-related inhibitor (ATRi), in patients with DNA damage repair (DDR) loss-of-function mutant tumors. RP-3500 was well tolerated, with no grade 4 mechanism-based anemia events seen in the trial and grade 3 events occurring at a rate of 24%. Moreover, RP-3500 monotherapy resulted in durable clinical benefits in several tumor types and genomic alterations, with the overall clinical benefit rate being 43%. Importantly, in patients with ovarian cancer, 85% of whom were platinum-refractory and resistant, and 90% of whom had previously been treated with a PARP inhibitor, the overall response rate was 25%, the clinical benefit rate was 75%, and the median progression-free survival was 35 weeks. In patients with BRCA1 and BRCA2 mutated cancers who were previously treated with a PARP inhibitor, the clinical benefit was 48%. Many clinical trials investigating RP-3500 alone and in combination with other agents are currently being undertaken. 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