Topical TLR7 agonist and radiotherapy in patients with metastatic breast cancer

• DOI: 10.1136/jitc-2024-011173
• Publication Date: 2025-04-05T13:41:12Z
• Authors: Sylvia Adams; Sandra Demaria; Darawan Rinchai; Ena Wang; Yelena Novik; Ruth Oratz; Maria Fenton-Keri...; Pascale G Levine; Xiaochun Li; Francesco Marincola; Ping Jin; David Stroncek; Judith Goldberg; Davide Bedognetti; Silvia Chiara For...
• Keywords: Imiquimod; TLR7

Background Toll-like receptor (TLR) agonists and radiation therapy hold promise for cancer immunotherapy. We conducted a phase I/II trial combining topical imiquimod (IMQ, TLR-7 agonist) local radiotherapy (RT) in patients with metastatic breast accompanied by longitudinal transcriptional analysis of tumor biopsies. Methods The primary objective the ( NCT01421017 ) was to assess systemic responses immune-related response criteria (irRC) after an 8-week cycle IMQ concurrent RT (cohort 1). An amendment added two cohorts, both received one dose cyclophosphamide (CTX) administered 1 week before study treatment initiation, IMQ/RT/CTX 2) RT/CTX control 3). Cutaneous metastases were prospectively assigned (area A) or alone B). Secondary objectives safety (Common Terminology Criteria Adverse Events criteria) skin metastases. In all tumors biopsied at 2 3 weeks. Results 31 enrolled (n=12, n=12, n=7, cohort 1, 2, 3, respectively), 4 out 24 cohorts showing (two complete (CR) partial (PR)). No observed seven arm (RT alone). well-tolerated, no grade 4–5 treatment-related adverse events occurred AEs manageable (anemia, pain, ulceration, n=1 each). Local 19/24 (9 CR 10 PR) 5/24 (5 areas treated combined IMQ-RT alone, respectively (p<0.001). All underwent serial biopsies, 84 samples yielded sufficient material analyses. These revealed that presence T-helper functional orientation microenvironment paralleled downregulation DNA-repair genes associated IMQ+RT, but not alone. post-treatment activation immune-effector functions stable progressing lesions. Conclusions Our findings support clinical efficacy recurrent cancer, evidence occasional antitumor activity. Trial registration number .