2026-04-13T04:11:47Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/122812024-11-29T08:27:15Zcom_2072_378072com_2072_378040col_2072_378100

Phase 2 study of the antitumour activity and safety of simlukafusp alfa (FAP-IL2v) combined with atezolizumab in patients with recurrent and/or metastatic cervical squamous cell carcinoma Verlingue, Loic Prenen, Hans Guerra Alia, Eva Maria Tosi, Diego ITALIANO, ANTOINE Perets, Ruth OAKNIN, ANA Quimioteràpia combinada Coll uterí - Càncer - Tractament Anticossos monoclonals - Ús terapèutic DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Uterine Cervical Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma, Squamous Cell CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales femeninos::neoplasias uterinas::neoplasias del cuello uterino Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::carcinoma de células escamosas COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados Cervical cancer; Immunotherapy; Squamous cell carcinoma Cáncer de cuello uterino; Inmunoterapia; Carcinoma de células escamosas Càncer de coll uterí; Immunoteràpia; Carcinoma de cèl·lules escamoses Background Simlukafusp alfa (FAP-IL2v) is an immune cytokine engineered to selectively promote immune responses in the tumour microenvironment. We evaluated the antitumour activity and safety of FAP-IL2v plus atezolizumab in recurrent and/or metastatic cervical squamous cell carcinoma (SCC) in a phase 2 basket study (NCT03386721). Methods Patients with confirmed metastatic, persistent or recurrent cervical SCC who had progressed on ≥1 anti-cancer therapy and had measurable disease were enrolled. FAP-IL2v 10 mg was administered once every 3 weeks (Q3W) or once weekly (QW) for 4 weeks then once every 2 weeks (Q2W) with the corresponding Q3W or Q2W atezolizumab regimens. The primary endpoint was objective response rate by investigator assessment. Findings Forty-eight patients were enrolled (Q3W: n = 47; QW/Q2W: n = 1). Among 45 response evaluable patients, objective responses occurred in 12 patients (27%; CI 16.0–41.0), including 3 complete and 9 partial responses. Responses occurred in 6/19 PD-L1 positive patients (32%; 95% CI 15.4–54.0) and 5/24 PD-L1 negative patients (21%; 95% CI 9.2–35.6). Median duration of response was 13.3 months (95% CI 7.6–NE). Median progression-free survival was 3.7 months (95% CI 3.3–9.0). Adverse events (AEs) were consistent with the known safety profile of each drug. AEs leading to withdrawal of either agent occurred in 6 patients (13%). Pronounced expansion and activation of natural killer and CD8 T cells in peripheral blood and increased tumour infiltration and inflammation were observed. Interpretation FAP-IL2v plus atezolizumab is clinically active and has manageable safety in patients with recurrent and/or metastatic cervical SCC. F. Hoffmann-La Roche Ltd. 2024-11-26T13:51:49Z 2024-11-26T13:51:49Z 2024-11 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion eBioMedicine;109 https://doi.org/10.1016/j.ebiom.2024.105374 Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess Elsevier Scientia