Efficacy and safety of combination therapy with envafolimab and lenvatinib in patients with endometrial cancer after failure of first-line platinum-based therapy.

5597 Background: The treatment options after first-line platinum-based doublet chemotherapy for endometrial cancer (EC) are still very limited in China, highlighting the substantial needs for second line and subsequent treatment of advanced EC. This trial aims to investigate the effects of Envafolimab, the world's first subcutaneously injectable anti-PD-L1 antibody approved by China's National Medical Products Administration, in combination with Lenvatinib for Chinese patients with advanced EC. Methods: This is a multicenter, multicorhort, open-label, phase Ⅱ study. Patients with pathologically confirmed advanced EC failed at least 1 prior lines of platinum-based chemotherapy were enrolled. Tumor tissue or biopsy specimens should be provided for central retrospective biomarker analysis. Patients in Envafolimab+Lenvatinib cohort received Envafolimab 400mg every 4 weeks subcutaneously plus Lenvatinib 20 mg once daily orally, in 4-week cycles. The primary endpoint was objective response rate (ORR), as assessed by blinded independent review committee (BIRC) per RECIST 1.1, in patients that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). Results: As of July 12, 2023, 32 patients from 28 centers had received Envafolimab+Lenvatinib treatment. The median number of previous systemic therapies in these patients was 1 (range: 1-5), and 15.6% of them had received more than two previous systemic therapies at study entry. Analysis of the primary endpoint was conducted in the 25 patients that is not MSI-H or dMMR and had received at least one efficacy evaluation. The confirmed ORR per BIRC was 40.0% (10/25, 95% CI 21.1%- 61.3%). Disease control rate (DCR) was 84.0% (21/25, 95% CI 63.9%-95.5%), and the median progression-free survival (PFS) was 9.2 months (95% CI 4.0-11.0). Of the 32 patients receiving combination treatment, the most common any-grade treatment-related adverse events (TRAEs) were hypothyroidism (59.4%), proteinuria (56.3%), hypertension (56.3%) and platelet count decreased (53.1%). Grade 3 or 4 TRAEs occurred in 62.5% (20/32) patients. No grade 5 TRAEs were reported. Conclusions: Envafolimab plus Lenvatinib showed robust antitumor activity with a manageable safety profile in patients with advanced EC who are not MSI-H or dMMR and have experienced disease progression after prior systemic therapy. Compared to the results from other intravenous anti-PD-1 antibody plus Lenvatinib in EC patients, Envafolimab with Lenvatinib had comparable efficacy and similar safety whilst a higher proportion of heavily pretreated patients were enrolled in this trial. Moreover, subcutaneous injection of Envafolimab plus Lenvatinib provided a more convenient dosing regimen in this population. Further evaluation of this combination therapy is underway. Clinical trial information: NCT05112991 .