Monotherapy of envafolimab in patients with high tumor mutational burden advanced solid tumors: Results from a phase II clinical trial.

Abstract

2595 Background: Tumor mutational burden (TMB) has emerged as a predictive biomarker of immune checkpoint blockade response in cancers. Envafolimab, a humanized single-domain anti-PD-L1 antibody subcutaneous administration (s.c.), has been approved in China for the treatment of advanced solid tumors with MSI-H. The study is to explore the potential anti-tumor activity in patients with TMB-high (TMB-H) in China. Methods: The study consists of two parts. Part 1 is to explore the association of single agent envafolimab activity with tissue TMB (tTMB) measured by Onco500 assay in patients with advanced solid tumors. Part 2 will further evaluate the efficacy of envafolimab in advanced solid tumor patients base on the cutoff of TMB value identified from Part 1. Envafolimab is administrated s.c. at 400 mg every 4 weeks until disease progression, adverse events, or other reasons causing treatment discontinuation. Efficacy and safety are assessed in all patients who received at least one dose of envafolimab. tTMB is assessed by a central lab using SimcereDx Onco500 assay (Jiangsu Simcere Medical Device Co., Ltd, China). The primary endpoint was objective response rate (ORR) assessed by independent review committee per RECIST v1.1 criteria. Results: As of Nov 15, 2024, a total of 70 patients with advanced cancers (colorectal cancer [9,12.6%], cervical cancer and soft tissue sarcoma [8 each; 11.4%], and other 18 tumor types) have received envafolimab in Part 1. 30 (42.9%) patients had received ≥3 systemic therapies (median 2; range 1-19). Median follow-up time was 31.2 months (range: 0.6-36.8). 49 (70%) patients had at least one treatment-related adverse events (TRAEs), and 6 (8.6%) had grade 3 or 4 TRAEs. The most common TRAEs were anemia and alanine aminotransferase increased (9 each; 12.9%). Grade 2 decreased appetite was the only TRAE resulting in treatment discontinuation. No treatment-related death reported. TMB≥13 mut/Mb with Onco500 panel was selected as the threshold of TMB-H based on the clinical data and previous comparison of platforms for determining TMB value in patients. Key efficacy outcomes are presented (Table). ORR and DOR were higher in patients with tTMB ≥13mut/Mb (33.3% and 20.2m) than patients with tTMB < 13mut/Mb (4.3% and 3.8m). Conclusions: tTMB could be a useful predictive biomarker for response to envafolimab in patients with pre-treated advanced solid cancer. The Part 2 of this study is ongoing (NCT04891198). Clinical trial information: NCT04891198 . tTMB≥13 mut/Mb(n = 24) tTMB<13 mut/Mb(n = 46) Objective response rate, n (%) [95% CI] 8 (33.3) [15.6-55.3] 2 (4.3) [0.5-14.8] Complete / partial response 1 (4.2) / 7(29.2) 0 (0) / 2 (4.3) Stable disease / progressive disease 2 (8.3) / 9 (37.5) 16 (34.8) / 24 (52.2) Median DoR, months (95% CI) 20.2 (4.4-NE) 3.8 (NE-NE) Median PFS, months (95% CI) 2.8 (1.8-8.7) 1.9 (1.8-3.6) Median OS, months (95% CI) 13.2 (5.7-NE) 12.7 (7.4-18.2)