Camrelizumab plus albumin-bound paclitaxel and S-1 as first-line treatment of HER-2 negative unresectable locally advanced or advanced gastric and gastroesophageal junction adenocarcinoma: A phase II clinical trial.

4038 Background: Gastric cancer is a common malignant tumor of the digestive tract. For nearly 90% of HER2 negative advanced gastric and gastroesophageal junction adenocarcinoma (G/GEJ) patients (pts), the current first-line treatment options and efficacy are limited, and new therapeutic drugs are urgently needed to improve the efficacy of advanced G/GEJ. Methods: This is a prospective, single center, single arm, open label phase II clinical trial involving HER-2 negative G/GEJ diagnosed by histopathology. Pts received 4-6 cycles of treatment with camrelizumab combined with albumin bound paclitaxel and S-1, followed by camrelizumab maintenance therapy until progression or 2 years. By following up with pts and evaluating clinical efficacy based on imaging examinations, the effectiveness and safety of the protocol can be assessed. Results: From December 2020 to December 2024, a total of 47 pts obtained informed consent based on exclusion criteria. As of the deadline (January 6, 2025), the average follow-up period was 17.4 months, with a median follow-up time of 16.7 months (range: 1.6-42.2 months). One patient had completed 2 years of treatment and ended maintenance therapy with camrelizumab, 5 pts (12.5%) were still receiving treatment, 34 pts (85.0%) stopped treatment, and 28 pts (70%) developed disease progression (PD). The best therapeutic effect was achieved in 2 cases with CR, 25 cases with PR, 11 cases with SD, and 2 cases with PD. The experiment reached the primary endpoint with an ORR of 67.5%. The secondary endpoint DCR was 95.0%, the median PFS was 7.8 months [95% confidence interval (CI): 6.2-9.4 months], and the median OS was 23.8 months [95% confidence interval (CI): 15.2-32.4 months]. For all study subjects, there was no correlation between OS, PFS, and baseline characteristics of the study (age, gender, ECOG, microsatellite status, mismatch repair protein status, EBER status, PDL1 level, number of metastatic sites, presence of liver metastasis, presence of lung metastasis, presence of abdominal metastasis, presence of bone metastasis). Among all enrolled pts, 36 experienced adverse events (76.6%) and 18 experienced grade 3-4 TRAE (38.3%), mainly bone marrow suppression and immune related rash. Conclusions: As the first-line treatment for HER-2 negative advanced gastric and gastroesophageal junction adenocarcinoma, the combination of Carilizumab with albumin bound paclitaxel and S-1 has shown encouraging efficacy. Clinical trial information: ChiCTR2300069672 .