Abstract
<div>Purpose:<p>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.</p>Patients and Methods:<p>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.</p>Results:<p>Sixty-one participants were enrolled. Dose-limiting toxicities included fatigue (flat dose 20 mg: <i>n =</i> 1), asthenia (25 mg: <i>n =</i> 1), drug-induced liver injury (uptitration regimen 20/25 mg: <i>n =</i> 1), transaminase increase (20/25 mg: <i>n =</i> 1), and pneumonia (20/35/35 mg: <i>n =</i> 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<sup>+</sup> T cells (including regulatory T cells), 2-fold; CD8<sup>+</sup> 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% (<i>n =</i> 3); disease control rate, 27.1% (<i>n =</i> 16)]. Responses were durable [<i>n =</i> 3, 2.8 (censored), 6.3, and 43.4 months].</p>Conclusions:<p>FAP-IL2v had a manageable safety profile and showed initial signs of antitumor activity in advanced/metastatic solid tumors.</p></div>
Published Version
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