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 metastatic, persistent or recurrent cervical SCC who had progressed on ≥1 anti-cancer 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), including 3 complete and 9 partial responses. Responses occurred in 6/19 PD-L1 positive patients (32%; 95% CI 15.4–54.0) and 5/24 PD-L1 negative patients (21%; 95% CI 9.2–35.6). Median duration of response was 13.3 months (95% CI 7.6–NE). Median progression-free survival was 3.7 months (95% CI 3.3–9.0). Adverse events (AEs) were consistent with the known safety profile 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 and inflammation were observed. Interpretation FAP-IL2v plus atezolizumab is clinically active and has manageable safety in patients with recurrent and/or metastatic cervical SCC.