2026-04-17T13:48:31Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/128002025-05-03T03:19:40Zcom_2072_378070com_2072_378040col_2072_378092

Phase Ib Study of Immunocytokine Simlukafusp Alfa (FAP-IL2v) Combined with Pembrolizumab for Treatment of Advanced and/or Metastatic Melanoma SORIA RIVAS, AINARA Sanmamed, Miguel F. MUÑOZ COUSELO, EVA Sandhu, Shahneen Long, Georgina Spreafico, Anna Anticossos monoclonals - Ús terapèutic Melanoma - Tractament Quimioteràpia combinada Pell - Càncer - Tractament DISEASES::Neoplasms::Neoplasms by Site::Skin Neoplasms DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neuroendocrine Tumors::Melanoma 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 CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized Other subheadings::Other subheadings::/therapeutic use ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias cutáneas ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::tumores neuroendocrinos::melanoma 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 COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales Otros calificadores::Otros calificadores::/uso terapéutico Immunocitocina simlukafusp alfa; Pembrolizumab; Melanoma avançat Inmunocitocina simlukafusp alfa; Pembrolizumab; Melanoma avanzado Immunocytokine simlukafusp alfa; Pembrolizumab; Advanced melanoma Purpose: This study explored the combination of fibroblast activation protein (FAP) IL2 variant (FAP-IL2v), a novel immune-cytokine, with pembrolizumab in patients with advanced and/or metastatic melanoma. Patients and Methods: This open-label, multicenter, phase Ib clinical study (NCT03875079) evaluated the safety, tolerability, pharmacodynamics, pharmacokinetics, and antitumor activity of FAP-IL2v (simlukafusp alfa, RO6874281) in combination with pembrolizumab. Patients with advanced and/or metastatic melanoma were either checkpoint inhibitor (CPI)-naïve or CPI-experienced. Patients received 10 mg FAP-IL2v either continuously once every 3 weeks (Q3W) or in an induction/maintenance setting consisting of a 3-week induction phase with weekly (QW) dosing followed by continuous Q3W dosing. Pembrolizumab was dosed Q3W at 200 mg. Results: Eighty-three patients were treated: 16 patients in two safety run-in cohorts and 67 patients in two extension cohorts; 75 (90.4%) patients were CPI-experienced. The pharmacokinetics of FAP-IL2v in combination with pembrolizumab was similar to that after administration as monotherapy. Consistent with the proposed mode of action, FAP-IL2v preferentially expanded NK and CD8 T cells. The most common FAP-IL2v–related grade 3/4 adverse events were lymphopenia (23%), elevated γ-glutamyltransferase (8%), elevated alanine aminotransferase (6%), and infusion-related reaction (6%). A response was observed in 5 of 75 (6.7%) CPI-experienced patients (all partial responses) and 2 of 8 CPI-naïve patients (one complete response and one partial response). The median progression-free survival was 3.1 months. Conclusions: The safety profile of FAP-IL2v in combination with pembrolizumab was manageable and consistent with the known safety profile. However, further exploration of FAP-IL2v and pembrolizumab was precluded in patients with melanoma with prior CPI due to the lack of clinical activity. Significance: In this phase Ib study, the combination of FAP-IL2v, an immune-cytokine developed to overcome the limitations of wild-type IL2, with the CPI pembrolizumab did not show meaningful antitumor activity in patients who had progressed on prior CPI therapy, suggesting that FAP-IL2v alone cannot overcome CPI resistance or unresponsiveness. This study was funded by F. Hoffmann-La Roche Ltd. 2025-05-03T03:19:40Z 2025-05-03T03:19:40Z 2025-05-03T03:19:40Z 2025-03-20T12:42:22Z 2025-03-20T12:42:22Z 2025-02-24 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/12800 Cancer Research Communications;5(2) https://doi.org/10.1158/2767-9764.CRC-24-0601 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess American Association for Cancer Research Scientia