1049P Phase Ib/II trial of envafolimab, a novel subcutaneous single-domain anti-PD-L1 monoclonal antibody, plus lenvatinib in patients with selected advanced solid tumors

Envafolimab is the world’s first subcutaneously injectable anti-PD-L1 antibody approved by China’s National Medical Products Administration with the injection time of less than 20 seconds. Here, we report the results from a phase Ib/II study of envafolimab plus lenvatinib in patients with selected advanced solid tumors. This was an open-label, multi-center trial. 6 patients with advanced solid tumors were enrolled in the phase Ib study for safety evaluation first, and then the phase II was divided into two cohorts. Cohort 1, PD-(L)1 inhibitor therapy resistant advanced non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Cohort 2, treatment naive advanced RCC. The objectives of phase Ib were to assess the safety and determine the recommended phase II dose (RP2D) for envafolimab plus lenvatinib. The primary endpoint of phase II was objective response rate (ORR) per RECIST v1.1. As cutoff date of March 31 2023, 24 patients were enrolled in phase Ib (n = 6) and the phase II expansion (n = 18). The RP2D was envafolimab 400mg every 4 weeks plus lenvatinib 20 mg/d. In PD-(L)1 resistant NSCLC (n=11), ORR was 27.3 % (95% CI: 6.0% to 61.0%), median duration of response (mDOR) was 4.2 months (95% CI: 3.7 to NE) and median progression-free survival (mPFS) was 8.1 months (95% CI: 1.8 to NE). In treatment naive RCC (n=5), ORR was 80.0% (95% CI: 28.4% to 99.5%), mDOR was NE (95% CI: NE to NE) and mPFS was NE (95% CI, NE to NE). The most common treatment-related adverse events (TRAEs) were proteinuria (75.0%), hypothyroidism (70.8%) and hypertension (62.5%). There were no grade 5 TRAEs and no TRAEs resulted in envafolimab or lenvatinib discontinuation. Envafolimab in combination with lenvatinib demonstrated a robust preliminary ORR and mPFS in PD-(L)1 resistant NSCLC patients with manageable safety profile. In consistent with the results from other intravenous anti-PD-1 antibody plus Lenvatinib in RCC patients, subcutaneous injection of envafolimab with lenvatinib provided a more convenient dose regimen in this population. Further evaluation of this combination therapy are underway in both populations.