Rimegepant Combined With AG Chemotherapy As First-Line Treatment For Metastatic Pancreatic Ductal Adenocarcinoma

This is a single-center, single-arm, prospective Phase Ib/II study designed to evaluate the clinical efficacy and safety profile of Rimegepant in combination with the AG (Nab-paclitaxel plus Gemcitabine) chemotherapy regimen as first-line treatment for patients with unresectable metastatic pancreatic cancer who have not received prior anti-pancreatic cancer therapy (surgical resection excepted).

Inclusion criteria

• The patient has good compliance, understands the study procedures, and has signed a written informed consent form.
• Age ≥ 18 years.
• Pathologically or cytologically confirmed pancreatic cancer, with imaging or pathological findings indicating unresectable pancreatic cancer with distant metastasis.
• Patients who have not received any prior treatment for pancreatic cancer (including radiotherapy, chemotherapy, or experimental therapy), except for surgical resection.
• If the patient has received neoadjuvant/adjuvant chemotherapy, the regimen must not contain AG, and the interval from the last administration to the diagnosis of recurrence must be >6 months, with no delayed toxicities.
• The patient has at least one measurable lesion according to the RECIST 1.1 criteria.
• ECOG performance status 0-1.
• Expected survival >3 months.
• Adequate organ function, defined as meeting the following criteria (blood tests to be completed within 14 days prior to enrollment):

• Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L
• Hemoglobin ≥90 g/dL
• Platelet count (PLT) ≥100 × 10⁹/L
• Total bilirubin <1.5 × upper limit of normal (ULN)
• Liver transaminases (AST & ALT) <2.5 × ULN; for patients with liver metastases, AST/ALT ≤5 × ULN
• Serum creatinine ≤1 × ULN, or creatinine clearance ≥50 mL/min if serum creatinine >1 × ULN
• The patient has an adequate nutritional status, defined as BMI >18.5 kg/m².
• Female patients who are not pregnant or breastfeeding; sexually active men and women of childbearing potential must use effective contraception during the study and for 6 months after treatment completion.
• No contraindications to remimazolam or AG chemotherapy agents.

Exclusion criteria

• Patients with a history of other malignancies within the past 5 years, except for cured in situ carcinoma or basal cell carcinoma of the skin.
• Patients diagnosed with pulmonary fibrosis or interstitial pneumonia within 28 days prior to enrollment.
• Patients with refractory pleural effusion or ascites.
• Patients with known brain or meningeal metastases.
• Patients who used strong CYP3A4 inducers within 3 weeks prior to the first study drug administration, or strong CYP3A4/UGT1A1 inhibitors within 3 weeks prior to the first study drug administration.
• Patients who underwent major organ surgery (excluding needle biopsy, central venous catheter insertion, port catheterization, biliary obstruction stenting, percutaneous transhepatic biliary drainage, and cholecystostomy) within 4 weeks prior to the first dose of study drug, or who plan to undergo elective surgery.
• Patients with known dihydropyrimidine dehydrogenase deficiency or low activity.
• Patients with active infection, including HIV infection, or chronic HBV/HCV in the active phase (HBV DNA ≥10⁴ copies/mL or ≥2000 IU/mL; patients must receive antiviral therapy first, and can only be enrolled when HBV DNA <10⁴ copies/mL or <2000 IU/mL, with continued antiviral therapy and monitoring of liver function and HBV viral load).
• Patients with severe comorbidities, including poorly controlled diabetes despite anti-diabetic medication, clinically significant active heart disease, renal failure, liver failure, uncontrolled epilepsy, history of central nervous system disease or mental disorder, hemorrhagic peptic ulcer, ileus, or intestinal obstruction.
• Patients with severe diarrhea (grade ≥2 per NCI-CTCAE v5.0: ≥4 bowel movements per day vs baseline; moderate/severe increase in stoma output; limitation of activities of daily living).
• Patients with severe psychiatric disorders.
• Patients with grade ≥II peripheral neuropathy at present or in the past.
• Patients with known hypersensitivity to benzodiazepines, AG chemotherapy agents, or related components.
• Patients who participated in other clinical trials within 4 weeks prior to enrollment.
• Patients deemed unsuitable for the trial by the investigator.