Journal: BMC medicine
Phase II neoadjuvant trial of serplulimab + SOX + thymalfasin in cStage III gastric/GEJ adenocarcinoma
Design:
- – Prospective, single-arm phase II study in patients 18–75 years with cStage III gastric or gastroesophageal junction adenocarcinoma, ECOG 0–1, adequate organ function.
- – Regimen: three 21-day cycles of serplulimab (anti–PD-1) + SOX (S-1, oxaliplatin) plus 9 weeks of thymalfasin, followed by curative minimally invasive gastrectomy.
- – Primary endpoint: pathologic complete response (pCR).
- – Secondary endpoints: major pathologic response (MPR), nodal downstaging, safety, survival, and correlative immune studies.
- – Immune monitoring via peripheral blood flow cytometry and bulk RNA-seq of PBMCs.
Efficacy:
- – 30 patients enrolled; all proceeded to curative-intent surgery.
- – pCR: 30.0% (9/30).
- – MPR: 56.7% (17/30).
- – ypN0: 63.3% (19/30); N-stage downstaging in 80.0% (24/30).
- – At median follow-up of 14.0 months (range 10.0–17.2):
- – One relapse (retroperitoneal nodal) at 14.4 months.
- – No deaths reported.
Safety:
- – Any-grade AEs: 93.3%.
- – Grade ≥3 AEs: 26.7%.
- – Immune-related AEs: 23.3%.
- – Overall safety described as acceptable for this intensive neoadjuvant approach.
Correlative immune findings:
- – Flow cytometry:
- – Expansion of CD8⁺ T cells with increased CD69 expression.
- – Reduction in HLA-DR⁺ T cells, interpreted as a shift from broad systemic activation to a more focused effector/memory response.
- – RNA-seq of PBMCs:
- – Thymalfasin-associated upregulation of genes for antigen processing/presentation and type I interferon signaling.
- – Identification of immune co-expression modules linked to treatment exposure and response.
Interpretation:
- – The combination of anti–PD-1, SOX, and thymalfasin as neoadjuvant therapy in stage III gastric/GEJ adenocarcinoma showed:
- – High pCR and MPR rates.
- – Substantial nodal clearance.
- – Manageable toxicity.
- – Immune and transcriptomic data support a working hypothesis that thymalfasin enhances and coordinates systemic antitumor immunity without excessive immune-related toxicity.
- – Authors conclude that results are promising and justify larger randomized trials to define added benefit and long-term outcomes.