Study Investigating the Association of NP137 With mFOLFIRINOX in Locally Advanced Pancreatic Ductal Adenocarcinoma

Study Overview
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Brief Summary
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The study will assess the safety of the association of NP137 with the standard of care mFOLFIRINOX in the treatment of locally advanced pancreatic ductal adenocarcinoma.The study drug which is tested is the NP137 in association with mFOLFIRINOX to allow a better tumor response as well as better survival outcomes with an acceptable safety.

Detailed Description
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The study is a multicentric, prospective, single arm phase 1b trial. This study will enroll 43 to 52 patients and consists of 2 parts: Safety Lead-in Phase and Expansion Phase. Initially, 3 to 12 patients will be enrolled into a Safety Lead-in Phase based on a 3 + 3 design, with the possibility of dose de-escalation, to confirm the recommended dose of NP137.The Expansion Phase will start after completion of Safety Lead-in Phase at the confirmed dose and will include 40 patients. Patients will be assigned to the experimental arm (NP137 + mFOLFIRINOX).

Official Title
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Study Investigating the Association of NP137 With mFOLFIRINOX in Locally Advanced Pancreatic Ductal Adenocarcinoma

Conditions
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Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Drug: NP137
* Drug: Oxaliplatin
* Drug: Irinotecan
* Drug: Calcium levofolinate
* Drug: 5 FU


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from 18 to 79 years Able to understand and sign informed consent Histologically or cytologically proven diagnosis of pancreatic ductal adenocarcinoma Locally advanced pancreatic cancer considered unresectable according to NCCN Guidelines® Version 2.2021 Measurable disease as defined by Response Evaluation Criteria in Solid Tumors RECIST 1.1 criteria Male, or non-pregnant and non-lactating female Women patients of childbearing potential* must have a negative serum/urine pregnancy test at screening and baseline, and be willing to use a highly effective** contraception. The patient should be advised to continue the contraception for at least 6 months following the completion of dosing. Women with cessation for > 24 months of previously occurring menses, or women of any age who have had a hysterectomy, or have had both ovaries removed will be considered to be of non-childbearing potential Male patients of reproductive potential must be willing to use one acceptable method of contraception, as judged by Investigator and Sponsor and/or to refrain from donating sperm from the time of screening through at least 6 months following the completion of dose administration No prior systemic therapy, radiation therapy, or resection for pancreatic cancer Life expectancy ≥ 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate liver function: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN), Bilirubin ≤ 1.5 x ULN or in subjects with biliary stenting ≤ 2.0 x ULN Alkaline phosphatase < 2.5 x ULN Subjects with biliary stenting do not need to wait for their alkaline phosphatase to become < 2.5 x ULN if their total bilirubin, AST and ALT have improved to within required study levels with criteria 12a and 12b Adequate bone marrow function: platelets >100,000 cells/mm3, hemoglobin > 9.0 g/dl and absolute neutrophil count (ANC) >1,500 cells/mm3 Adequate renal function: creatinine < 1.5 x ULN, creatinine clearance ≥ 30 mL/min/m2 Adequate nutritional state with Albumin ≥ 2.5 g/dL Less than grade 2 pre-existing peripheral neuropathy (per CTCAE) Patients covered by Health Insurance System Exclusion Criteria: Patients with resectable pancreatic cancer Evidence of the presence of metastases. Patients who have received prior systemic therapy, radiation therapy, or resection for pancreatic cancer or prior therapy with NP137 Patients with known Dihydropyrimidine dehydrogenase (DPD) deficiency, or homozygosity for UGT1A1*28 polymorphism (UGT1A1 genotype analysis is not required to be eligible) Previous (within the past 3 years) or concurrent malignancy diagnosis except non-melanoma skin cancer and in situ carcinomas (excluding in situ breast cancer) History of severe (grade ≥ 3) allergic reactions to one of the components of chemotherapy, or NP137 Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, may decrease subject's compliance to study's procedures or may render the patient at high risk from treatment complications in the opinion of the treating investigator Subjects with known poorly controlled comorbid conditions, including; congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), uncontrolled diabetes mellitus (DM) or neurologic disorders (not acutely related to pancreatic cancer) or limited function Major surgery within 4 weeks prior to signing informed consent form. Biliary stents are permitted History of allergy or hypersensitivity to human, humanized or chimeric monoclonal antibodies History of allergy or hypersensitivity to any of the chemotherapy agents belonging to mFOLFIRINOX regimen Subjects with a history of chronic HCV, HBV or HIV infection Subjects who have been administered a live vaccine within four weeks prior to the first administration of therapy Subjects who cannot stop chronic medications that inhibit or induce CYP2C8 or CYP3A4 Persons referred to in Articles L1121-5 to L1121-8 of the French code of public health (this corresponds to all persons protected: pregnant or parturient women, breastfeeding mothers, persons deprived of liberty by judicial or administrative decision, persons subject to a legal protection measure) Patients who have active infection requiring systemic therapy (other than HCV, HBV, HIV). Patients who participate or plan to participate in another interventional clinical trial.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Interventional Model Description: Multicentric prospective single arm phase 1b trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>NP137+ mFOLFIRINOX | Drug: NP137<br>* NP137 will be administrated at the first day of each cycle (CnD1) of 14 days as an IV infusion at 9 or 14 mg/kg.<br>Drug: Oxaliplatin<br>* Oxaliplatin will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 85 mg/m²<br>Drug: Irinotecan<br>* Irinotecan will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 150 mg/m²<br>Drug: Calcium levofolinate<br>* Calcium levofolinate will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 100 mg/m²<br>Drug: 5 FU<br>* 5 FU will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 2400 mg/m2 as a continuous intravenous infusion over 46 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Proportion of patients experiencing adverse events | Percentage Proportion of patients experiencing adverse events (AEs) of any grade and grade 3/4 AEs as defined by the National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE v 5.0) at 6 months. | At 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best overall objective response rate (ORR) | Best overall objective response rate (ORR) according to RECIST 1.1 | At 2,4 and 6 months |