Study to Assess the Safety, Tolerability of JPI-547 in Combination With Modified FOLFIRINOX or Gemcitabine-nab-paclitaxel in Patients With Locally Advanced and Metastatic Pancreatic Cancer

In combination with JPI-547 and chemotherapy in patients with locally advanced/metastatic pancreatic cancer,

Primary Objectives

• To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D).
• To select the optimal combination chemotherapy based on the safety profile.

Secondary Objectives

• To assess the safety and toxicity.
• To evaluate anti-tumor activity.

Inclusion criteria

[Phase 1b/2]

• Histologically or cytologically confirmed inoperable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC)
• Those with at least one measurable lesion in accordance with RECIST 1.1
• Those with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Those with an expected survival period ≥12 weeks
• Patients with adequate hematologic function, renal and hepatic function confirmed by the following criteria (During the screening period, laboratory tests can be retested only once.)
• Those who voluntarily decide to participate in this clinical study after hearing sufficient explanations and who consent in writing

[only to Phase 2]

• Subjects from whom tumor tissue samples can be obtained at screening and who meet at least one of the following criteria:

• Tumor tissue samples stored prior to screening are available
• Tumor tissue samples can be obtained at screening with the subject's consent to biopsy

Exclusion criteria

[Phase 1b/2]

• Those with a history of severe hypersensitivity to the investigational product or combination anticancer drugs.
• Those with the following medical history or surgical history/procedural history confirmed

• Other primary malignant tumors other than pancreatic cancer
• Major surgery that requires general anesthesia or breathing aid
• Severe cardiovascular disease
• New York Heart Association Class 3 or 4 heart failure
• Severe cerebrovascular disease t
• Pulmonary thrombosis, deep vein thrombosis, or bronchial asthma, obstructive pulmonary disease, and other life-threatening severe lung diseases
• Infections requiring administration of systemic antibiotics or antivirals, etc.
• Hematologic malignancy
• Those with the following diseases

• Massive ascites, pleural effusions requiring therapeutic paracentesis
• Neuropathy ≥Grade 2
• Diarrhea, chronic inflammatory bowel disease
• Intestinal paralysis, intestinal obstruction
• Diseases that make oral administration difficult or affect absorption
• Interstitial lung disease, pulmonary fibrosis
• Dialysis patient
• Patients with clinically significant symptoms or uncontrolled central nervous system or brain metastases

j. Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure >90 mmHg) k. Bleeding diatheses l. Active hepatitis B or C virus. m. Known human immunodeficiency virus (HIV) positive

• Those with a medication history of the following drugs

• Anti-cancer drug therapy such as chemotherapy and biological therapy
• Radiation therapy within 2 weeks of baseline
• Those who are taking or expected to require administration of strong inhibitors or inducers of CYP3A4
• (For mFOLFIRINOX cohort) Those who are taking or expected to require administration of sorivudine
• Patients who require continuous administration of non-steroidal anti-inflammatory drugs (NSAIDs) with high bleeding risk
• Patients requiring continuous administration of systemic corticosteroid equivalent to prednisone >10 mg/day
• Those who have received antithrombotic agents, including antiplatelet agents, anticoagulants, etc.
• Pregnant women, lactating women, or women of childbearing potential and men who do not intend to practice abstinence or use appropriate contraceptive methods for until 6 months for men and 9 months for women after administration of the investigational product and during the clinical study
• Those who have administered other investigational products or have received investigational medical device procedures within 4 weeks of the baseline
• Other patients who are inappropriate or unable to participate in this clinical study at the discretion of the investigator