Study of Immunotherapy Combined With Chemotherapy in Locally Advanced and Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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To evaluate the efficacy of PD-L1/CTLA4 BsAb for the second line treatment and the combination with chemotherapy for the first line treatment in pancreatic cancer

Detailed Description
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Subjects who signed the informed consent were assigned to three cohorts according to the actual treatment status. Cohort 1 enrolled subjects receiving PD-L1/CTLA4 BsAb 5mg/kg iv Q2W for 2nd treatment; cohort 2 enrolled subjects receiving PD-L1/CTLA4 BsAb in combination with gemcitabine/albumin- paclitaxel as 1st treatment for 4-6 cycles with PD-L1/CTLA4 BsAb monotherapy maintainence; cohort 3 enrolled subjects received systemic chemotherapy, receiving PD-L1/CTLA4 BsAb combined with oxaliplatin / irinotecan / leucovorin / fluorouracil (FOLFIRINOX) as 1st treatment for 4-6 cycles withPD-L1/CTLA4 BsAb monotherapy maintainence; until disease progression according to RECIST 1.1, intolerable toxicity, withdrawal, death, 2-yr treatment,who comes first.

Official Title
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Multicenter, Open-label Clinical Study of PD-L1/CTLA4 BsAb Combined With Chemotherapy in Locally Advanced and Metastatic Pancreatic Cancer

Conditions
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Locally Advanced and Metastatic Pancreatic Cancer

Intervention / Treatment
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* Drug: PD-L1/CTLA4 BsAb
* Combination Product: GP
* Combination Product: FOLFIRINOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histology or cytology confirmed as pancreatic ductal adenocarcinoma; ECOG 0-1; adequate organ function (absolute neutrophil count ≥1.5 x 109/L; platelet count ≥100 x 109/L; creatinine < 1.5 x ULN (upper normal) or calculated creatinine clearance ( CRCI) ≥ 60mL/min; albumin ≥ 30g/L; total bilirubin <1.5 x ULN; aspartate aminotransferase (AST) < 2.5 x ULN; alanine aminotransferase (ALT) < 2.5x ULN; INR or PT < 1.5x ULN, and aPTT <1.5x ULN); no obvious symptoms of jaundice and ascites; no other serious underlying diseases Exclusion Criteria: patients with active brain metastases; history of autoimmune diseases, or need to be treated with corticosteroids and immunosuppressive agents; past history of unstable angina, symptomatic congestive heart failure, severe arrhythmia, myocardial infarction within 6 months, QT interval prolongation (>450ms); other malignant tumors within the last 5 years; pregnant or lactating women; NRS ≥ 4 points; unintentional weight loss ≥ 5% within 1 month before the first dose even if peripheral or central vein nutrition support,

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PD-L1/CTLA4 BsAb<br>For 2nd line treatment，PD-L1/CTLA4 BsAb 5mg/kg Q2W | Drug: PD-L1/CTLA4 BsAb<br>* PD-L1/CTLA4 BsAb 5mg/kg, iv，Q2W<br>|
| Experimental: PD-L1/CTLA4 BsAb + GP<br>For 1st line treatment，PD-L1/CTLA4 BsAb 5mg/kg Q2W in combination with Gemcitabine 1000 mg/m2 and Nab-paclitaxel 125 mg/m2 , 28days/cycle | Drug: PD-L1/CTLA4 BsAb<br>* PD-L1/CTLA4 BsAb 5mg/kg, iv，Q2W<br>Combination Product: GP<br>* Gemcitabine 1000mg/m2, iv, D1,8,15, 28days/cycle; nab-Paclitaxel 125mg/m2，iv，D1,8,15, 28days/cycle;<br>* Other names: nab-Paclitaxel;|
| Experimental: PD-L1/CTLA4 BsAb + FOLFIRINOX<br>For 1st line treatment，PD-L1/CTLA4 BsAb 5mg/kg Q2W in combination with Oxaliplatin 68 or 85 mg/m2, Irinotecan 135 or 150 or 180 mg/m2, Calcium Folate 400 mg/m2, Fluorouracil 2400mg/m2, 14 days/cycle | Drug: PD-L1/CTLA4 BsAb<br>* PD-L1/CTLA4 BsAb 5mg/kg, iv，Q2W<br>Combination Product: FOLFIRINOX<br>* Fluorouracil 2400mg/m2，iv，D1, 14days/cycle; Oxaliplatin 68-85mg/m2，iv, D1,14days/cycle;Irinotecan135-180mg/m2，iv, D1, 14days/cycle;Calcium Folate 400mg/m2，iv, D1, 14days/cycle;<br>* Other names: Fluorouracil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | objective response rate | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DCR | Disease Control Rate | 2 years | 
| DOR | Duration of Response | 2 years | 
| TTP | Time to Response | 2 years | 
| PFS | Progression Free Survival | 2 years | 
| OS | Overall Survival | 2 years |