Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD1 antibody in phase Ib/II clinical trial NCT02915432

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High tumor mutational burden (TMB-H) is correlated with enhanced objective response rate (ORR) and progression-free survival (PFS) for certain cancers receiving immunotherapy. This study aimed to investigate the safety and efficacy of toripalimab, a humanized PD-1 antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1.

Patients and methods

We reported on the AGC cohort of phase Ib/II trial evaluating the safety and activity of toripalimab in patients with AGC, oesophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma. In Cohort 1, 58 chemo-refractory AGC patients received toripalimab (3 mg/Kg d1, Q2W) as a monotherapy. In Cohort 2, 18 chemotherapy-naive AGC patients received toripalimab (360 mg d1, Q3W) with oxaliplatin 130 mg/m2 qd, d1, capecitabine 1000 mg/m2 BID, d1-d14, Q3W as first-line treatment. Primary endpoint was ORR. Biomarkers such as PD-L1 and TMB were evaluated for correlation with clinical efficacy.


In Cohort 1, the ORR was 12.1% and the disease control rate (DCR) was 39.7%. Median PFS was 1.9 months and median OS was 4.8 months. The TMB-H group showed significant superior OS than the TMB-L group [14.6 vs 4.0 months, HR = 0.48 (96% CI 0.24 to 0.96), p=0.038], while PD-L1 overexpression did not correlate with significant survival benefit. 77.6% of patients experienced at least one treatment-related adverse event (TRAE), and 22.4% of patients experienced a grade 3 or higher TRAE. In cohort 2, the ORR was 66.7% and the DCR was 88.9%. 94.4% of patients experienced at least one TRAE and 38.9% of patients experienced grade 3 or higher TRAEs.


Toripalimab has demonstrated a manageable safety profile and promising anti-tumor activity in AGC patients, especially in combination with XELOX. High TMB may be a predictive marker for OS of AGC patients receiving toripalimab as a single agent.

Trial registration NCT02915432

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