Efficacy of Sintilimab Combined With Bevacizumab and XELOX/SOX in Initially Unresectable AFP-positive Gastric/Gastroesophageal Junction Adenocarcinoma

Conversion Therapy of Sintilimab Combined With Bevacizumab and XELOX/SOX for Initially Unresectable AFP-positive Gastric/Esophagogastric Junction Adenocarcinoma : A Multi-center, Single-arm, Phase II Trial (SOLIDS-02)

Alpha-fetoprotein-producing gastric cancer (AFP-positive gastric cancer, AFP-GC), a rare and highly aggressive subtype of gastric cancer, accounts for 1.3% to 15% of all gastric cancer cases. Its clinical features are significantly different from those of common gastric cancer. Not only does it show abnormally elevated serum AFP levels, but it also has a stronger angiogenic ability, a higher rate of distant metastasis, and a poorer prognosis even after a upfront R0 surgery, making it a challenging problem in the field of gastric cancer treatment. Notably, patients with AFP-positive gastric cancer have a relatively low sensitivity to the traditional standard regimens. There is an urgent need to explore targeted treatment strategies to break through the efficacy bottleneck.

Combination of sintilimab, bevacizumab and XELOX/SOX for initially unresectable AFP-positive gastric/esophagogastric junction adenocarcinoma could be a novel therapeutic strategy to increase response rate and therapeutic efficacy. This study is a multi-center, single-arm phase 2 clinical trial to evaluate efficacy, tolerability and safety of perioperative sintilimab in combination with bevacizumab and XELOX/SOX in initially unresectable AFP-positive gastric/esophagogastric junction adenocarcinoma.

Inclusion Criteria:

• Signed informed consent;
• Patients age 18-75 years;
• Histologically CT/MRI confirmed cT3-4N+M0/1 gastric or GEJ adenocarcinoma; (M1 only includes type I liver metastasis of gastric cancer, according to the "Chinese Expert Consensus on Liver Metastasis of Gastric Cancer");
• Serum AFP levels > 2× upper limit of normal or AFP-positive by IHC staining;
• Adequate organ function
• ECOG 0-1, no surgery contraindications;
• Expected survival ≥3 months;

Exclusion Criteria:

• HER2-positive status: IHC 3+, or IHC 2+/FISH+

• Prior chemotherapy, radiotherapy, anti-PD-1/PD-L1 therapy, surgery for gastric cancer;

• Signs of other distant metastases (e.g., peritoneal, lung, bone, supraclavicular lymph, etc.)

• Significant cardiovascular disease

  --Current treatment with anti-viral therapy or HBV

• Pregnancy or breastfeeding

• History of malignancy within 5 years prior to screening

• Present or history of any autoimmune disease or immune deficiency;

• There are active gastric and duodenal ulcers, ulcerative colitis and other gastrointestinal diseases, or active bleeding in unresectable tumors.