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

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability of JPI-547 in combination with modified FOLFIRINOX (mFOLFIRINOX) or Gemcitabine-nab-paclitaxel (GemAbraxne) in patients with locally advanced and metastatic pancreatic cancer

Detailed Description
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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.

Official Title
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An Open-label, Dose-finding, Phase Ib Study to Assess the Safety, Tolerability of JPI-547, a Dual Inhibitor of PARP/Tankyrase, in Combination With Modified FOLFIRINOX (mFOLFIRINOX) or Gemcitabine-nab-paclitaxel (GemAbraxne) in Patients With Locally Advanced and Metastatic Pancreatic Cancer

Conditions
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Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Drug: JPI-547
* Drug: modified FOLFIRINOX
* Drug: Gemcitabine-nab-paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 79 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: Arm A (mFOLFIRINOX)<br>JPI-547 and Combination Chemotherapy(mFOLFIRINOX) The study is conducted in a 3+3 dose escalation method. | Drug: JPI-547<br>* Subjects are administered this investigational product once a week for 5 days, and have wash-out period for 2 days (5 Days on-2 Days off). The investigational product is administered orally in a fasting state for 2 hours before and after meals at the same time (e.g., a certain time in the morning). Capsules should be swallowed whole and should not be chewed, crushed or split.<br>Drug: modified FOLFIRINOX<br>* After IV administration of Oxaliplatin 65 mg/m2 for 2 hours After IV administration of Leucovorin 400 mg/m2 for 2 hours + IV administration of Irinotecan 135 mg/m2 for 90 minutes (Irinotecan is started 30 minutes after the start of Leucovorin administration and administered simultaneously during the last 90 minutes of Leucovorin administration, but administered separately using a Y-connector without mixing) Continuous IV infusion of 5-FU 2400 mg/m2 for 46 hours Repeated administration every 2 weeks on a 14-day cycle<br>|
| Experimental: Arm B (GemAbraxane)<br>JPI-547 and Combination Chemotherapy (Gemcitabine-nab-paclitaxel) The study is conducted in a 3+3 dose escalation method. | Drug: JPI-547<br>* Subjects are administered this investigational product once a week for 5 days, and have wash-out period for 2 days (5 Days on-2 Days off). The investigational product is administered orally in a fasting state for 2 hours before and after meals at the same time (e.g., a certain time in the morning). Capsules should be swallowed whole and should not be chewed, crushed or split.<br>Drug: Gemcitabine-nab-paclitaxel<br>* After IV administration of nab-paclitaxel 100 mg/m2 for 30 minutes IV administration of Gemcitabine 1000 mg/m2 for 30 minutes Administration on Days 1, 8, and 15 on a 28-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). | The MTD is determined according to the traditional 3+3 rule-based method for each combination therapy, and it is defined as the highest dose with a DLT incidence of less than 1/3 or 2/6 subjects. | From the date of administration to 4 weeks (DLT period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the adverse events, drug adverse events, and serious adverse events evaluated by NCI-CTCAE v5.0 |  | Until 4 weeks after the last dose administration | 
| To evaluate anti-tumor activity. | Anti-tumor activity is evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | Evaluation at 8 weeks intervals through study completion from the date of study entry until the date of progression, up to 18 months |