Efficacy and Safety Evaluation of Sintilimab in Combination With IBI310 as Treatment in Patients With EBV-Positive Gastric Cancer
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Neoadjuvant therapy group
|
Drug: Sintilimab
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.
Drug: IBI310
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.
|
| Experimental: first-line therapy group
|
Drug: Sintilimab
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.
Drug: IBI310
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.
|
| Experimental: ≥second-line therapy group
|
Drug: Sintilimab
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.
Drug: IBI310
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.
|
Outcome Measures
Primary Outcome Measures
- Arms 1: Neoadjuvant therapy group [Approximately 40 months after the first participant is randomized]
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
- Arms 2: first-line therapy group [Approximately 40 months after the first participant is randomized]
Objective response rate(ORR): Objective response rate(ORR) of Sintilimab in combination with IBI310 in all participants in this group.
- Arms 3:≥second-line therapy group [Approximately 40 months after the first participant is randomized]
Objective response rate(ORR): Objective response rate(ORR) of Sintilimab in combination with IBI310 in all participants in this group.
Secondary Outcome Measures
- Arms 1: Neoadjuvant therapy group [Approximately 40 months after the first participant is randomized]
R0 resection rate
- Arms 1: Neoadjuvant therapy group [Approximately 40 months after the first participant is randomized]
Event free survival(EFS)
- Arms 1: Neoadjuvant therapy group [Approximately 40 months after the first participant is randomized]
Objective response rate(ORR)
- Arms 1: Neoadjuvant therapy group [Approximately 40 months after the first participant is randomized]
Disease control rate(DCR)
- Arms 1: Neoadjuvant therapy group [Approximately 40 months after the first participant is randomized]
Overall survival(OS)
- Arms 1: Neoadjuvant therapy group [Approximately 40 months after the first participant is randomized]
Number of participants experiencing clinical and laboratory adverse events (AEs).
- Arms 2: first-line therapy group [Approximately 40 months after the first participant is randomized]
Progression-free survival (PFS）
- Arms 2: first-line therapy group [Approximately 40 months after the first participant is randomized]
Disease control rate (DCR）
- Arms 2: first-line therapy group [Approximately 40 months after the first participant is randomized]
Overall survival (OS）
- Arms 2: first-line therapy group [Approximately 40 months after the first participant is randomized]
( Number of participants experiencing clinical and laboratory adverse events (AEs).
- Arms 3:≥second-line therapy group [Approximately 40 months after the first participant is randomized]
Progression-free survival (PFS）
- Arms 3:≥second-line therapy group [Approximately 40 months after the first participant is randomized]
Disease control rate (DCR)
- Arms 3:≥second-line therapy group [Approximately 40 months after the first participant is randomized]
Overall survival (OS）
- Arms 3:≥second-line therapy group [Approximately 40 months after the first participant is randomized]
Number of participants experiencing clinical and laboratory adverse events (AEs)
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Cancer Hospital | Beijing | Beijing | China | 100142 |
Sponsors and Collaborators
- Peking University
- Innovent Biologics (Suzhou) Co. Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CIBI310Y101