Data from AZD8701, an Antisense Oligonucleotide Targeting FOXP3 mRNA, as Monotherapy and in Combination with Durvalumab: A Phase I Trial in Patients with Advanced Solid Tumors

• DOI: 10.1158/1078-0432.c.7815565
• Publication Date: 2025-05-13T19:39:38Z
• Authors: Lillian L. Siu; Sophie Postel-Vinay; Rafael Villanueva...; Guillermo de Velasco; Eduardo Castanon ...; Christos E. Kyria...; Melissa Johnson; Kaïssa Ouali; Stephen McMorn; Helen K. Angell; Felicia Ng; Shashank Saran; Mahdiye Bayat; Teresa Collins; Archana Roy; Arthur W. Lambert; Song Cho; Neil Miller; Michele Petruzzelli; John Stone; Christophe Massard
• Keywords: Durvalumab; Solid tumor

<div>AbstractPurpose:<p>AZD8701 uses next-generation antisense oligonucleotide (ASO) technology to selectively reduce human forkhead box P3 (FOXP3) expression in regulatory T cells, reversing their immunosuppressive function. <i>FOXP3</i> ASO alone or with PD-(L)1 inhibition attenuated tumor growth mice. We report a phase I study of AZD8701 combined durvalumab patients advanced solid tumors.</p>Patients and Methods:<p>Eligible had tumors received prior standard-of-care treatment, including anti–PD-(L)1 therapy. Patient cohorts were treated intravenously weekly at escalating doses, either (60–960 mg) (240–720 1,500 mg intravenous every 4 weeks. The primary objective was safety tolerability, the aim determining MTD.</p>Results:<p>Forty-five monotherapy, 18 durvalumab. One dose-limiting toxicity (increased alanine aminotransferase) occurred 960 mg. most common adverse events related monotherapy fatigue (22.2%), asthenia, pyrexia, increased aminotransferase (20% each); profile similar when With 24.4% 15.6% stable disease for ≥16 ≥24 weeks, respectively; one patient 720 partial response. mRNA changes heterogeneous (8/13 showed reduction), no clear dose relationship. accumulated epithelium stroma.</p>Conclusions:<p>This demonstrates clinical feasibility therapy, generally manageable events, knockdown, delivery tumor.</p></div>