Clinical trial NCT06475326: Adebrelimab in Combination With NALIRIFOX in Locally Advanced Pancreatic Cancer
Official title: A Phase II Trial of Adebrelimab in Combination With NALIRIFOX for Conversion Therapy in Locally Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pancreatic Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2024-06-26
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: In this study, Adebrelimab combined with NALIRIFOX conversion therapy was performed in subjects with locally advanced pancreatic cancer to evaluate the efficacy and safety of conversion therapy with immunotherapy combined with chemotherapy, followed by different treatment methods such as surgery, continued conversion therapy, and advanced systemic therapy according to different transformation outcomes, to improve the survival benefit of subjects with locally advanced pancreatic cancer.

Detailed description: In this study, Adebrelimab combined with NALIRIFOX conversion therapy was performed in subjects with locally advanced pancreatic cancer to evaluate the efficacy and safety of conversion therapy with immunotherapy combined with chemotherapy, followed by different treatment methods such as surgery, continued conversion therapy, and advanced systemic therapy according to different transformation outcomes, to improve the survival benefit of subjects with locally advanced pancreatic cancer.

To assess the surgical resection conversion rate of chemotherapy in addition to immunotherapy for unresectable locally advanced pancreatic cancer (LAPC).

To evaluate the changes in CA19-9 levels, objective response rate (ORR), R0/R1 resection rate, pathologic response (pCR/MPR), event-free survival (EFS), 1 year and 2 years and overall survival (1y-OS, 2y-OS, OS) before and after conversion therapy for unresectable locally advanced pancreatic cancer.

To assess perioperative safety (including surgical morbidity and mortality within 60 days). To evaluate the safety and tolerability of immunotherapy in combination with chemotherapy for conversion therapy for unresectable locally advanced pancreatic cancer.

Eligibility criteria: Inclusion Criteria:

1. Age 18-75 years old;
2. Histologically or cytologically confirmed pancreatic ductal adenocarcinoma (preferably histologically confirmed);
3. Judged by the investigator to be unresectable locally advanced (unresectable criteria refer to the guidelines for the diagnosis and treatment of pancreatic cancer);
4. Total bilirubin ≤ 2 mg/dL (subjects with bile duct stents can be enrolled if bilirubin ≤ 2 mg/dL and no cholangitis after stent placement);
5. Have not received previous treatment for pancreatic cancer, including radiotherapy, chemotherapy, surgery, etc;
6. Have at least one measurable lesion (per RECIST 1.1 criteria). ECOG score is 0\~1 points within 28 days before the first dose, laboratory tests with adequate organ function: Blood routine: WBC ≥3.0×109/L; ANC≥1.5×109/L；PLT≥100×109/L； HGB≥90 g/L; Liver function: AST≤2.5×ULN; ALT≤2.5×ULN； TBIL≤1.5×ULN; Renal function: Cr≤1.5×ULN or CrCl ≥60 mL/min; Coagulation function: INR≤1.5, APTT≤1.5×ULN ; There was no obvious abnormality in ECG.
7. Male subjects, as well as females of childbearing potential, must use contraception for 3 months from the start of the first dose to the last use of the study drug.

Exclusion Criteria:

1. Occurrence of distant metastases (for imaging suspicion of peritoneal cancer or ascites, histological or cytological verification such as laparoscopic exploration is required)
2. Medical history and complications: Subject has contraindications to surgical resection of pancreatic cancer; Subject has any known active autoimmune disease; Subject has any complications requiring systemic treatment with glucocorticoids such as prednisone (\>10mg/day) or has used immunosuppressive drugs within 14 days prior to the first dose; Subject has received tumor vaccine or other immune-activating antitumor drugs (such as interferon, interleukin, thymosin or immune cell therapy) within 1 month before the first dose; Subjects are participating in other clinical trials or have received drug intervention from other clinical trials within 4 weeks prior to the first dose.; Subject has other malignancies requiring treatment; Subject has had a significant prior cardiovascular disease; Subject has a known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
3. Laboratory tests: Subject tested positive for HIV serologically; Active hepatitis B (HbsAg positive and HBV-DNA ≥103copies/mL) or active hepatitis C (HCV antibody positive and HCV-DNA positive with the need for antiviral therapy).
4. Presence of allergies and adverse drug reactions: Presence of allergy or hypersensitivity to monoclonal antibodies; Presence of allergic reactions to leucovorin, 5-FU, irinotecan, oxaliplatin
5. Diseases or abnormal laboratory indicators that in the opinion of the investigator will affect the results of the study, or are not in the interest of the subjects, should be excluded.

Primary outcomes:
measure: Surgical Conversion Rate
timeFrame: 8 weeks
Secondary outcomes:
measure: Pathologic response rate (pCR/MPR)
timeFrame: up to approximately 1 years
measure: Objective response rate (ORR)
timeFrame: up to approximately 1 years
measure: Event-free survival (EFS)
timeFrame: up to approximately 1 years
measure: Overall survival (OS)
timeFrame: up to approximately 1 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
affiliation: Fudan University
name: Weijing Zhang
role: STUDY_CHAIR
References: