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

Abstract

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 fi rmed metastatic, persistent or recurrent cervical SCC who had progressed on >= 1 anticancer 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), - 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) - 54.0) and 5/24 PD-L1 negative patients (21%; 95% CI 9.2-35.6). - 35.6). Median duration of response was 13.3 months (95% CI 7.6-NE). - NE). Median progression- free survival was 3.7 months (95% CI 3.3-9.0). - 9.0). Adverse events (AEs) were consistent with the known safety profile fi le 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 fi ltration and inflammation fl ammation were observed. Interpretation FAP-IL2v plus atezolizumab is clinically active and has manageable safety in patients with recurrent and/or metastatic cervical SCC.