Verlingue Loic, Italiano Antoine, Prenen Hans, Guerra Alia Eva Maria, Tosi Diego, Perets Ruth, Lugowska Iwona, Moiseyenko Vladimir, Gumus Mahmut, Arslan Cagatay, Lindsay Colin R, Deva Sanjeev, Taus Álvaro, Oaknin Ana, Rottey Sylvie, Cicin Irfan, Goksu Sema Sezgin, Smolin Alexey, Roselló-Keränen Susana, Habigt Christin, Marbach Daniel, Boetsch Christophe, Dejardin David, Sleiman Nassim, Evers Stefan, Richard Muriel, Ardeshir Caroline, Charo Jehad, Kraxner Anton, Teichgräber Volker, Keshelava Nino, Dziadziuszko Rafal
Gustave Roussy Institute of Oncology, Villejuif, France.
Institut Bergonié Cancer Center, Bordeaux, France.
EBioMedicine. 2024 Nov;109:105374. doi: 10.1016/j.ebiom.2024.105374. Epub 2024 Oct 11.
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).
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.
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.
FAP-IL2v plus atezolizumab is clinically active and has manageable safety in patients with recurrent and/or metastatic cervical SCC.
F. Hoffmann-La Roche Ltd.
西姆卢卡福斯α（FAP-IL2v）是一种经过基因工程改造的免疫细胞因子，旨在选择性地促进肿瘤微环境中的免疫反应。在一项2期篮子研究（NCT03386721）中，我们评估了FAP-IL2v联合阿特珠单抗治疗复发性和/或转移性宫颈鳞状细胞癌（SCC）的抗肿瘤活性和安全性。
纳入确诊为转移性、持续性或复发性宫颈SCC且在≥1种抗癌治疗中进展且具有可测量病灶的患者。FAP-IL2v 10mg每3周给药1次（Q3W）或每周给药1次（QW），共4周，然后每2周给药1次（Q2W），同时采用相应的Q3W或Q2W阿特珠单抗给药方案。主要终点是研究者评估的客观缓解率。
共纳入48例患者（Q3W组：n = 47；QW/Q2W组：n = 1）。在45例可评估缓解的患者中，12例患者出现客观缓解（27%；CI 16.0-41.0），包括3例完全缓解和9例部分缓解。在19例PD-L1阳性患者中有6例出现缓解（32%；95%CI 15.4-54.0），在24例PD-L1阴性患者中有5例出现缓解（21%；95%CI 9.2-35.6）。中位缓解持续时间为13.3个月（95%CI 7.6-未达到）。中位无进展生存期为3.7个月（95%CI 3.3-9.0）。不良事件（AE）与每种药物已知的安全性特征一致。导致停用任何一种药物的AE发生在6例患者中（13%）。观察到外周血中自然杀伤细胞和CD8 T细胞明显扩增和活化，肿瘤浸润和炎症增加。
FAP-IL2v联合阿特珠单抗在复发性和/或转移性宫颈SCC患者中具有临床活性且安全性可控。
F. Hoffmann-La Roche Ltd.
