Envafolimab combined with lenvatinib and albumin-bound paclitaxel in previously treated advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma: a prospective, phase II, multi-cohort trial

Clinical Snapshot

Key Findings

• P Value: No significant difference between groups: PFS P=0.629, OS P=0.873

• Effect Size: Disease control rate: 100% in both groups

• Primary Outcome: ORR: 60.0% (Group A), 46.7% (Group B)

• Nnt Or Sensitivity: Number needed to treat approximately 2 patients for one objective response in Group A

• Confidence Interval: mPFS Group A: 8.2 months (95% CI 6.1-10.4); Group B: 5.9 months (95% CI 3.8-8.1)

Clinical Application

Requires access to envafolimab (subcutaneous PD-L1 inhibitor), lenvatinib, and albumin-bound paclitaxel; intensive monitoring needed given 100% adverse event rate Envafolimab not currently TGA-approved; lenvatinib and albumin-bound paclitaxel available but not PBS-listed for this indication; would require special access scheme consideration Patients with HER2-negative, MSS advanced gastric/GEJ adenocarcinoma after first-line treatment failure, particularly those without prior immunotherapy exposure

Abstract

BACKGROUND: This single-center, open-label, exploratory trial aimed to investigate the efficacy and safety of envafolimab combined with lenvatinib and chemotherapy in previous treated advanced G/GEJ adenocarcinoma. METHODS: Eligible patients with HER2-negative, microsatellite stable (MSS) advanced G/GEJ adenocarcinoma who had progressed after first-line treatment were enrolled in this phase II trial. Patients without previously receiving PD-1/PD-L1 inhibitors were enrolled in Group A, and those who progressed on the first-line PD-1 inhibitors were included in Group B. Patients in both groups received envafolimab (200 mg, subcutaneous injection (sc), days 1 and 15, Q4W) combined with lenvatinib and albumin-bound paclitaxel (100 mg/m2, IV, days 1, 8 and 15, Q4W, up to 6 cycles) until disease progression, unacceptable toxicity, or refusal of continuation. The primary endpoint was objective response rate (ORR). RESULTS: A total of 30 patients were included for safety and efficacy analysis. As of data cutoff (Sep 14, 2024), the median follow-up was 17.0 months (IQR: 8.0-18.8) in Group A. The ORR was 60.0%, and the DCR was 100.0%. The mPFS was 8.2 months (95% CI 6.1-10.4) with mOS of 14.8 months (95% CI 7.4-22.2). With a median follow-up of 9.0 months (IQR: 6.1-16.2) in Group B, the ORR was 46.7%, and the DCR was 100.0%. The mPFS was 5.9 months (95% CI 3.8-8.1), and the mOS was 11.5 months (95% CI 3.1-19.9). The overall incidence of adverse events (AEs) of any grade was 100%. While Group A showed numerically better outcomes than Group B, there was no statistically significant difference in PFS (P = 0.629) or OS (P = 0.873) between the two groups. CONCLUSIONS: Second-line envafolimab-based combination therapy demonstrated promising effects in previously treated advanced GC, particularly in those who have not previously received ICIs.

References

1. 1.Zhao, X., Feng, W., Geng, Q., Huang, M., Zhang, Z., Chen, J., Sheng, X., Zhu, X., & Guo, W. (2026). Envafolimab combined with lenvatinib and albumin-bound paclitaxel in previously treated advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma: a prospective, phase II, multi-cohort trial. Cancer Immunology, Immunotherapy. https://doi.org/10.2217/nnm-2022-0300