Envafolimab in combination with lenvatinib and albumin paclitaxel for previously treated advanced gastric/gastroesophageal junction adenocarcinoma: Preliminary analysis of a phase II, two-cohort study.

Abstract

e16039 Background: The combination of first-line chemotherapy and PD-1 has emerged as a standard treatment, enhancing the efficacy in advanced gastric/gastroesophageal junction (GEJ) cancer. The efficacy of the combination of second-line chemotherapy and PD-1/PD-L1 remains unclear. This study aims to observe the efficacy of Envafolimab plus tyrosine kinase inhibitors (TKIs) and second-line chemotherapy in the treatment of patients with advanced GEJ adenocarcinoma. Methods: This prospective, open-label, phaseⅡ, two cohort study was conducted to assess the efficacy and safety of Envafolimab-based therapy in patients experiencing progression after initial first-line treatment. Eligible patients with HER2-negative, microsatellite stable (MSS), advanced GEJ adenocarcinoma were consecutively enrolled and assigned into cohort A or cohort B, according to whether they received PD-1 inhibitors in the first-line treatment. Patients in both cohorts received Envafolimab (200mg, hypodermic injection, days 1 and 15, Q4W) combined with Lenvatinib (8mg/12mg, po, once a day) and albumin paclitaxel (100mg/m2, IV, days 1, 8 and 15, Q4W, up to 6 cycles) until disease progression, unacceptable toxicity, or patients refusal to continue treatment. The primary endpoint was objective response rate(ORR) per iRECIST v1.1, and the secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. The efficacy and safety data in this analysis were from patients in cohort A who previously failed in first-line chemotherapy and did not receive PD-1 or PD-L1 inhibitors ever. Results: From October 2022 to June 2023, cohort A enrolled 16 patients, and 15 of them were evaluable for efficacy analysis. The average age was 58.87 ±11.81 years, 80% patients were male. 6 patients had been tested for PD-L1 status, of which 1 (16.7%) was positive and 5 (83.3%) were negative. As of Jan29, 2024, the median follow-up was 10.6 months (95%CI = 8.67-12.53), the median number of treatment cycles was 7 cycles (IQR: 5, 8). Based on the iRECIST v1.1, the ORR was 60.00% (90% CI = 35.96%-80.91%), the DCR was 100.00% (90% CI = 81.90%-100.00%). The median PFS (mPFS) was 8.23 months (90% CI =6.27-8.61), and the median OS (mOS) was 10.6 months (90% CI =8.79-12.15). Overall incidences of adverse events (AEs) of any grade was 100%, and 75.00% (n = 12) had ≥ grade 3 AEs during treatment. Most treatment-related adverse events (TRAEs) of grade ≥3 included neutrophil count (56.25%), decreased leukocyte count (37.5%). Conclusions: In patients of advanced gastric cancer who have not previously received PD-1/PD-L1 inhibitors, this second-line combination therapy demonstrates promising preliminary effects. Clinical trial information: NCT06030934 .