First-line envafolimab in combination with recombinant human endostatin and chemotherapy for advanced squamous non-small cell lung cancer: Updated results from a prospective, single-arm, multicenter phase II study.

Abstract

8573 Background: Immunotherapy combined with chemotherapy has been established as the standard first-line treatment for patients with advanced squamous NSCLC (sq-NSCLC) without oncogenic driver mutations. Antiangiogenic drugs enhance immunotherapy efficacy by normalizing blood vessels and remodeling the tumor microenvironment. However, they pose a high bleeding risk in sq-NSCLC treatment. Recombinant human endostatin (Rh-endostatin), the only approved agent for sq-NSCLC, can prolong survival without increasing bleeding risk. This trial aimed to investigate the efficacy and safety of Envafolimab, the first approved subcutaneous single-domain anti-PD-L1 antibody, plus Rh-endostatin and chemotherapy as first-line treatment for advanced sq-NSCLC. Methods: This prospective, single-arm, multicenter, phase II trial was conducted at 3 research centers in China (NCT05243355). Patients with pathologically confirmed primary advanced or locally advanced unresectable sq-NSCLC. were enrolled. Patients received Envafolimab (300 mg, subcutaneously, day 1) and Rh-endostatin (210 mg, continuous intravenous infusion over 72 hours, day 1-3) combined with paclitaxel (175mg/m 2 , day 1) or albumin paclitaxel (260 mg/m 2 , day 1), and cisplatin (75 mg/m 2 , day 1-3), or carboplatin ( AUC 5, IV, day 1); every 3 weeks for 4-6 cycles, followed by maintenance Envafolimab until disease progression (PD), unacceptable toxicity, or patient refusal. The primary endpoint was the 1-year PFS rate, and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and tolerability. Results: From December 2021 to December 2024, 33 eligible patients were enrolled, 26 of whom were included in the safety and efficacy analysis. As of December 16, 2024, the median follow-up was 16.5 months (95%CI: 8.1, NA). According to RECIST v1.1, the ORR was 65.4%, and the DCR was 96.2%. The median PFS (mPFS) was 12.4 months (95%CI: 11.4, NA) with a 1-year PFS rate of 59.9% (95%CI: 43.0%, 83.3%). The median OS (mOS) was 24.6 months (95%CI: 12.2, NA) with 1-year OS rate of 70.7% (95%CI: 54.2%, 92.1%) and a 2-year OS rate of 54.7% (95%CI: 36.9%, 81.1%). Overall, adverse events (AEs) of any grade were reported in 84.8% (28/33) of patients. The most common AEs were myelosuppression, alopecia, and nausea, which were more likely to be chemotherapy-related. 33.3% (11/33) of patients experienced immune-related AEs (irAEs). No unexpected AEs were observed. Conclusions: Our results demonstrated that Envafolimab in combination with Rh-endostatin and chemotherapy resulted in favorable clinical outcomes with a manageable safety profile, representing a promising treatment modality as first-line therapy for advanced sq-NSCLC. Clinical trial information: NCT05243355 .