TY - JOUR
T1 - Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity from a Phase I Study of Simlukafusp Alfa (FAP-IL2v) in Advanced/Metastatic Solid Tumors
AU - Steeghs, Neeltje
AU - Gomez-Roca, Carlos
AU - Rohrberg, Kristoffer S
AU - Mau-Sørensen, Morten
AU - Robbrecht, Debbie
AU - Tabernero, Josep
AU - Ahmed, Samreen
AU - Rodriguez-Ruiz, Maria E
AU - Ardeshir, Caroline
AU - Schmid, Daniela
AU - Sleiman, Nassim
AU - Watson, Carl
AU - Piper-Lepoutre, Hanna
AU - Dejardin, David
AU - Evers, Stefan
AU - Boetsch, Christophe
AU - Charo, Jehad
AU - Teichgräber, Volker
AU - Melero, Ignacio
PY - 2024/7/1
Y1 - 2024/7/1
N2 - PURPOSE: 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.PATIENTS AND METHODS: 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.RESULTS: 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].CONCLUSIONS: FAP-IL2v had a manageable safety profile and showed initial signs of antitumor activity in advanced/metastatic solid tumors.
AB - PURPOSE: 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.PATIENTS AND METHODS: 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.RESULTS: 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].CONCLUSIONS: FAP-IL2v had a manageable safety profile and showed initial signs of antitumor activity in advanced/metastatic solid tumors.
KW - Adult
KW - Aged
KW - Endopeptidases/administration & dosage
KW - Female
KW - Humans
KW - Interleukin-2/administration & dosage
KW - Male
KW - Maximum Tolerated Dose
KW - Membrane Proteins
KW - Middle Aged
KW - Neoplasm Metastasis
KW - Neoplasms/drug therapy
KW - Recombinant Fusion Proteins/pharmacokinetics
KW - Treatment Outcome
UR - http://www.scopus.com/inward/record.url?scp=85197955408&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-23-3567
DO - 10.1158/1078-0432.CCR-23-3567
M3 - Journal article
C2 - 38630781
SN - 1078-0432
VL - 30
SP - 2693
EP - 2701
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 13
ER -