American Association for Cancer Research
ccr-23-3567_supplementary_table_s1_suppts1.pdf (75.66 kB)

Supplementary Table S1 from Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity from a Phase I Study of Simlukafusp Alfa (FAP-IL2v) in Advanced/Metastatic Solid Tumors

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journal contribution
posted on 2024-07-01, 07:24 authored by Neeltje Steeghs, Carlos Gomez-Roca, Kristoffer S. Rohrberg, Morten Mau-Sørensen, Debbie Robbrecht, Josep Tabernero, Samreen Ahmed, Maria E. Rodríguez-Ruiz, Caroline Ardeshir, Daniela Schmid, Nassim Sleiman, Carl Watson, Hanna Piper-Lepoutre, David Dejardin, Stefan Evers, Christophe Boetsch, Jehad Charo, Volker Teichgräber, Ignacio Melero

Supplementary Table S1. Study representation of underserved communities.



Simlukafusp alfa [fibroblast activation protein α–targeted IL2 variant (FAP-IL2v)], a tumor-targeted immunocytokine, comprising an IL2 variant moiety with abolished CD25 binding fused to human IgG1, is directed against fibroblast activation protein α. This phase I, open-label, multicenter, dose-escalation, and extension study (NCT02627274) evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of FAP-IL2v in patients with advanced/metastatic solid tumors. Participants received FAP-IL2v intravenously once weekly. Dose escalation started at 5 mg; flat dosing (≤25 mg) and intraparticipant uptitration regimens (15/20, 20/25, 20/20/35, and 20/35/35 mg) were evaluated. Primary objectives were dose-limiting toxicities, maximum tolerated dose, recommended expansion dose, and pharmacokinetics. Sixty-one participants were enrolled. Dose-limiting toxicities included fatigue (flat dose 20 mg: n = 1), asthenia (25 mg: n = 1), drug-induced liver injury (uptitration regimen 20/25 mg: n = 1), transaminase increase (20/25 mg: n = 1), and pneumonia (20/35/35 mg: n = 1). The uptitration regimen 15/20 mg was determined as the maximum tolerated dose and was selected as the recommended expansion dose. Increases in peripheral blood absolute immune cell counts were seen for all tested doses [NK cells, 13-fold; CD4+ T cells (including regulatory T cells), 2-fold; CD8+ T cells, 3.5-fold] but without any percentage change in regulatory T cells. Clinical activity was observed from 5 mg [objective response rate, 5.1% (n = 3); disease control rate, 27.1% (n = 16)]. Responses were durable [n = 3, 2.8 (censored), 6.3, and 43.4 months]. FAP-IL2v had a manageable safety profile and showed initial signs of antitumor activity in advanced/metastatic solid tumors.