Efficacy and Safety of Sintilimab in Combination with Concurrent Chemoradiotherapy for Locally Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (SHARED): Study Protocol of a Prospective, Multi-Center, Single-Arm Phase 2 Trial

Abstract

Purpose: Concurrent chemoradiotherapy (cCRT) is the mainstay therapy of locally advanced gastric (G) and gastroesophageal junction (GEJ) cancers with a poor prognosis. Programmed cell death receptor-1 (PD-1) inhibitor has been approved and recommended to treat ≥3 line G/GEJ patients. A significant clinical benefit of PD-1 inhibitors in addition to cCRT has been observed in locally advanced lung cancer. Sintilimab, a humanized IgG4 monoclonal antibody with high affinity and specificity for PD-1, has shown promising efficacy with an overall response rate of 85% in combination with chemotherapy in gastric cancer in a phase Ib study (NCT02937116).

Patients and methods: SHARED is a prospective, multicentre, single-arm Phase II trial in China, exploring the efficacy of sintilimab in combination with cCRT in locally advanced G/GEJ adenocarcinoma. According to a Simon optimal two-stage clinical design, 34 patients will be enrolled. All the eligible patients will receive one cycle of induction chemotherapy (S-1 plus nab-PTX) combined with sintilimab, followed by cCRT (radiotherapy plus nab-PTX) combined with sintilimab. Prior to the surgery, patients will receive another cycle of chemotherapy (S-1 plus nab-PTX) combined with sintilimab. In the adjuvant setting, all participants will be treated with 3 cycles of chemotherapy (S-1 plus nab-PTX) combined with sintilimab. The primary endpoint is the rate of pathological complete response (pCR). The secondary endpoints include disease-free survival (DFS), major pathological response (MPR), R0 resection rate, surgical AEs, overall survival (OS), event-free survival (EFS), and safety profile. Moreover, the prognostic value of tumor biomarkers and immune biomarkers will be explored.

Conclusion: SHARED is designed to primally evaluate the efficacy and safety of sintilimab in combination with cCRT in locally advanced G/GEJ cancers and to prospectively validate the prognostic value of tumor biomarkers and immune biomarkers.

Keywords: anti-PD-1; chemoradiotherapy; immunotherapy; induction chemotherapy.

Conflict of interest statement

Innovent Biologics, Inc. provided the sintilimab, but had no role in study design, or writing of the protocol. The authors report no other conflicts of interest in this work.

© 2022 Wei et al.

Figures

Figure 1

Schematic diagram of SHARED regimen. All patients will receive one cycle of S-1 (40mg/m2, PO, Bid, D1 to D14) and nab-PTX (100–120mg/m2, IV, D1 and D8) in combination with sintilimab (200mg, IV, D1) for 3 weeks, followed by radiation therapy (45Gy/1.8Gy in 25 factions) with nab-PTX (80–100 mg/m2, IV, D1, D8, D15, and D22) and sintilimab (200mg, IV, D1 and D22) for 5 weeks. One to three weeks after the completion, patients will receive one cycle of S-1 (40mg/m2, PO, Bid, D1 to D14) and nab-PTX (100–120mg/m2, IV, D1 and D8) in combination with sintilimab (200mg, IV, D1). All patients will be operated on within 1 to 3 weeks later. The adjuvant therapy will start in 4–6 weeks after the operation with 3 cycles (3 weeks) of S-1 (40mg/m2, PO, Bid, D1 to D14 of each cycle), nab-PTX (100–120mg/m2, IV, D1 and D8 of each cycle) and sintilimab (200mg, IV, D1 of each cycle).

Figure 2

Simon optimal two stage design for SHARED study. At stage 1, nine patients who meet the inclusion criteria will be enrolled. If one or more patients demonstrate pCR, the study will advance to stage 2 to include 25 additional patients.