Efficacy and Safety Evaluation of Sintilimab in Combination With IBI310 as Treatment in Patients With EBV-Positive Gastric Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of sintilimab+ IBI310 for EBV-Positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Official Title
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Efficacy and Safety Evaluation of Sintilimab in Combination With IBI310 as Treatment in Patients With Gastric Cancer

Conditions
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Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

Intervention / Treatment
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* Drug: Sintilimab
* Drug: IBI310


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has histologically confirmed diagnosis of unresectable locally advanced,recurrent or metastatic gastric or GEJ malignant tumor (including squamous carcinoma, adenocarcinoma, Signet-ring cell carcinoma). Confirmed EBV positive determined by in situ hybridization (ISH), analyzed with tumor tissue sample, either from a previous surgery or biopsy , within last 6 months Male or Female at least 18 years of age Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Has adequate organ function. Expected survival>=12 weeks Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test at the timing of enrollment. Participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 6 months after the last dose of study medication. Applied to Arms 1: Has histologically confirmed gastric/GEJ malignant tumor, and were regarded as having clinical stage T3-T4aN0M0 or T2～4aN+M0 Applied to Arms 2: Had no prior systemic treatment for metastatic disease. Applied to Arms 3: Received ≥1 prior systemic treatment for metastatic disease. Exclusion Criteria: Has received prior therapy with an anti-programmed death (PD)-1, antiPD-L1, anti-PD L2, anti-CTLA-4 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor Is currently participating in and receiving study therapy ,except those in the survival follow up period of an investigational agent study or non-interventional study . Received systemic treatment with corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 4 weeks of first dose. Inhaled or topical steroids ,adrenal replacement steroid doses and steroid of prevention allergic reaction of i.v. contrast agent are permitted in the absence of active autoimmune disease. Received a live vaccine within 4 weeks of the first dose of study medication or plan to receive live vaccine during study period. Has had major surgery (craniotomy, thoracotomy or laparotomy) within 4 weeks prior to first dose of study medication, or anticipation of the need for major surgery during the course of study treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant therapy group<br> | Drug: Sintilimab<br>* Arms 1: Neoadjuvant therapy group 20 patients Drug: Sintilimab Weight<60Kg: 3mg/kg Q3W Weight>=60Kg:200 mg Q3W on Day 1 by IV infusion; Intervention：Perioperative Sintilimab+IBI310 are administered for 1-3 (6-18 weeks) cycles followed by 4 postoperative cycles (12 weeks) with Sintilimab monotherapy . Arms 2: first-line therapy group, 30 patients Drug: Sintilimab Weight<60Kg: 3mg/kg Q3W Weight>=60Kg:200 mg Q3W on Day 1 by IV infusion; Intervention：Sintilimab + IBI310 are administered for 1-3 (6-18 weeks) cycles followed by Sintilimab monotherapy for up to 2 years. Arms 3: ≥second-line therapy group, 30 patients Drug: Sintilimab Weight<60Kg: 3mg/kg Q3W Weight>=60Kg:200 mg Q3W on Day 1 by IV infusion; Intervention：Sintilimab + IBI310 are administered for 1-3 (6-18 weeks) cycles followed by Sintilimab monotherapy for up to 2 years.<br>Drug: IBI310<br>* Arms 1: Neoadjuvant therapy group, 20 patients Drug: IBI310 1 mg/kg Q6W on Day 1 by IV infusion. Intervention：Perioperative Sintilimab+ IBI310 are administered for 1-3 (6-18 weeks) cycles followed by 4 postoperative cycles (12 weeks) with Sintilimab monotherapy . Arms 2: first-line therapy group, 30 patients Drug: IBI310 1 mg/kg Q6W on Day 1 by IV infusion. Intervention：Sintilimab + IBI310 are administered for 1-3 (6-18 weeks) cycles followed by Sintilimab monotherapy for up to 2 years. Arms 3: ≥second-line therapy group, 30 patients Drug: IBI310 1 mg/kg Q6W on Day 1 by IV infusion. Intervention：Sintilimab + IBI310 are administered for 1-3 (6-18 weeks) cycles followed by Sintilimab monotherapy for up to 2 years.<br>|
| Experimental: first-line therapy group<br> | Drug: Sintilimab<br>* Arms 1: Neoadjuvant therapy group 20 patients Drug: Sintilimab Weight<60Kg: 3mg/kg Q3W Weight>=60Kg:200 mg Q3W on Day 1 by IV infusion; Intervention：Perioperative Sintilimab+IBI310 are administered for 1-3 (6-18 weeks) cycles followed by 4 postoperative cycles (12 weeks) with Sintilimab monotherapy . Arms 2: first-line therapy group, 30 patients Drug: Sintilimab Weight<60Kg: 3mg/kg Q3W Weight>=60Kg:200 mg Q3W on Day 1 by IV infusion; Intervention：Sintilimab + IBI310 are administered for 1-3 (6-18 weeks) cycles followed by Sintilimab monotherapy for up to 2 years. Arms 3: ≥second-line therapy group, 30 patients Drug: Sintilimab Weight<60Kg: 3mg/kg Q3W Weight>=60Kg:200 mg Q3W on Day 1 by IV infusion; Intervention：Sintilimab + IBI310 are administered for 1-3 (6-18 weeks) cycles followed by Sintilimab monotherapy for up to 2 years.<br>Drug: IBI310<br>* Arms 1: Neoadjuvant therapy group, 20 patients Drug: IBI310 1 mg/kg Q6W on Day 1 by IV infusion. Intervention：Perioperative Sintilimab+ IBI310 are administered for 1-3 (6-18 weeks) cycles followed by 4 postoperative cycles (12 weeks) with Sintilimab monotherapy . Arms 2: first-line therapy group, 30 patients Drug: IBI310 1 mg/kg Q6W on Day 1 by IV infusion. Intervention：Sintilimab + IBI310 are administered for 1-3 (6-18 weeks) cycles followed by Sintilimab monotherapy for up to 2 years. Arms 3: ≥second-line therapy group, 30 patients Drug: IBI310 1 mg/kg Q6W on Day 1 by IV infusion. Intervention：Sintilimab + IBI310 are administered for 1-3 (6-18 weeks) cycles followed by Sintilimab monotherapy for up to 2 years.<br>|
| Experimental: ≥second-line therapy group<br> | Drug: Sintilimab<br>* Arms 1: Neoadjuvant therapy group 20 patients Drug: Sintilimab Weight<60Kg: 3mg/kg Q3W Weight>=60Kg:200 mg Q3W on Day 1 by IV infusion; Intervention：Perioperative Sintilimab+IBI310 are administered for 1-3 (6-18 weeks) cycles followed by 4 postoperative cycles (12 weeks) with Sintilimab monotherapy . Arms 2: first-line therapy group, 30 patients Drug: Sintilimab Weight<60Kg: 3mg/kg Q3W Weight>=60Kg:200 mg Q3W on Day 1 by IV infusion; Intervention：Sintilimab + IBI310 are administered for 1-3 (6-18 weeks) cycles followed by Sintilimab monotherapy for up to 2 years. Arms 3: ≥second-line therapy group, 30 patients Drug: Sintilimab Weight<60Kg: 3mg/kg Q3W Weight>=60Kg:200 mg Q3W on Day 1 by IV infusion; Intervention：Sintilimab + IBI310 are administered for 1-3 (6-18 weeks) cycles followed by Sintilimab monotherapy for up to 2 years.<br>Drug: IBI310<br>* Arms 1: Neoadjuvant therapy group, 20 patients Drug: IBI310 1 mg/kg Q6W on Day 1 by IV infusion. Intervention：Perioperative Sintilimab+ IBI310 are administered for 1-3 (6-18 weeks) cycles followed by 4 postoperative cycles (12 weeks) with Sintilimab monotherapy . Arms 2: first-line therapy group, 30 patients Drug: IBI310 1 mg/kg Q6W on Day 1 by IV infusion. Intervention：Sintilimab + IBI310 are administered for 1-3 (6-18 weeks) cycles followed by Sintilimab monotherapy for up to 2 years. Arms 3: ≥second-line therapy group, 30 patients Drug: IBI310 1 mg/kg Q6W on Day 1 by IV infusion. Intervention：Sintilimab + IBI310 are administered for 1-3 (6-18 weeks) cycles followed by Sintilimab monotherapy for up to 2 years.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arms 1: Neoadjuvant therapy group | Pathological complete regression (pCR): Pathological complete regression (pCR) is defined as the proportion of patients with pathological complete regression (TRG1a) over the total number of patients evaluated centrally by the study pathologist | Approximately 40 months after the first participant is randomized | 
| Arms 2: first-line therapy group | Objective response rate(ORR): Objective response rate(ORR) of Sintilimab in combination with IBI310 in all participants in this group. | Approximately 40 months after the first participant is randomized | 
| Arms 3:≥second-line therapy group | Objective response rate(ORR): Objective response rate(ORR) of Sintilimab in combination with IBI310 in all participants in this group. | Approximately 40 months after the first participant is randomized | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arms 1: Neoadjuvant therapy group | R0 resection rate | Approximately 40 months after the first participant is randomized | 
| Arms 1: Neoadjuvant therapy group | Event free survival(EFS) | Approximately 40 months after the first participant is randomized | 
| Arms 1: Neoadjuvant therapy group | Objective response rate(ORR) | Approximately 40 months after the first participant is randomized | 
| Arms 1: Neoadjuvant therapy group | Disease control rate(DCR) | Approximately 40 months after the first participant is randomized | 
| Arms 1: Neoadjuvant therapy group | Overall survival(OS) | Approximately 40 months after the first participant is randomized | 
| Arms 1: Neoadjuvant therapy group | Number of participants experiencing clinical and laboratory adverse events (AEs). | Approximately 40 months after the first participant is randomized | 
| Arms 2: first-line therapy group | Progression-free survival (PFS） | Approximately 40 months after the first participant is randomized | 
| Arms 2: first-line therapy group | Disease control rate (DCR） | Approximately 40 months after the first participant is randomized | 
| Arms 2: first-line therapy group | Overall survival (OS） | Approximately 40 months after the first participant is randomized | 
| Arms 2: first-line therapy group | ( Number of participants experiencing clinical and laboratory adverse events (AEs). | Approximately 40 months after the first participant is randomized | 
| Arms 3:≥second-line therapy group | Progression-free survival (PFS） | Approximately 40 months after the first participant is randomized | 
| Arms 3:≥second-line therapy group | Disease control rate (DCR) | Approximately 40 months after the first participant is randomized | 
| Arms 3:≥second-line therapy group | Overall survival (OS） | Approximately 40 months after the first participant is randomized | 
| Arms 3:≥second-line therapy group | Number of participants experiencing clinical and laboratory adverse events (AEs) | Approximately 40 months after the first participant is randomized |