Ampligen Compared to No Treatment Following FOLFIRINOX in Subjects With Locally Advanced Pancreatic Adenocarcinoma

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of Ampligen in patients with locally advanced pancreatic adenocarcinoma

Detailed Description
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This is a Phase 2, randomized, open-label controlled study to evaluate the efficacy and safety of Ampligen treatment compared to a control group / no treatment following FOLFIRINOX treatment in subjects with locally advanced pancreatic adenocarcinoma.

Official Title
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A Phase 2, Randomized, Open-Label, Controlled Study to Evaluate the Efficacy and Safety of Ampligen® Compared to Control Group / No Treatment Following FOLFIRINOX in Subjects With Locally Advanced Pancreatic Adenocarcinoma

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Rintatolimod


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological diagnosis of pancreatic adenocarcinoma confirmed pathologically: Unresectable pancreatic cancer; locally advanced pancreatic cancer. Measurable disease per RECIST v.1.1. Completion of at least four (4) months of first line FOLFIRINOX treatment and no disease progression per RECIST v.1.1 as confirmed by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan 4 to 12 weeks after last FOLFIRINOX treatment. Male or non-pregnant, non-lactating female, ≥18 years or age. Negative pregnancy test for female subjects. Women of child-bearing potential (WOCBP) and Women not of child-bearing potential are eligible to participate. Both women of child-bearing potential and women of non-child-bearing potential should use an approved method of birth control and agrees to continue to use this method for the duration of the study and for 90 days after last treatment. Acceptable methods of contraception include abstinence, female subject/partner's use of hormonal contraceptive (oral, implanted, or injected) in conjunction with a barrier method (WOCBP only), female subject/partner's use of an intrauterine device (IUD), or if the female subject/partner is surgically sterile or two years post-menopausal. All male subjects/partners must agree to use a condom consistently and correctly for the duration of the study and for 90 days after last treatment. In addition, subjects may not donate sperm for the duration of the study and for 90 days after last treatment. Females who are less than two (2) years post-menopausal, those with tubal ligations and those using contraception must have a negative serum pregnancy test at baseline within the one (1) week prior to the first study medication infusion. Every six weeks, and at study termination a pregnancy test should be performed, either serum or urine stick test. However, if the urine result is positive, a serum pregnancy test will be performed. Any pregnancy that occurs while taking Ampligen® should be recorded using a Pregnancy Report Form and reported immediately to AIM ImmunoTech, Inc. Provide signed written informed consent and willingness, ability to comply with study requirements. Minimum weight of 40kg at baseline. Karnofsky Performance Status of 80 or higher at baseline. Subject must have a projected life expectancy of ≥ 3 months in the opinion of the Investigator. Subject has adequate organ function by the following laboratory assessments at baseline (obtained ≤ 21 days prior to Randomization): Hematologic Platelets ≥ 100×109/L Hemoglobin ≥ 9.0 g/dL Absolute Neutrophil Count (ANC) ≥ 1.5×109/L Absolute lymphocyte count ≥ 3 x 109/L Hepatic AST/ALT ≤ 3×ULN (if liver metastases are present, ≤ 5×ULN) Alkaline phosphatase ≤ 2.0×ULN (if liver metastases are present, ≤ 5×ULN) Total bilirubin ≤ 1.5×ULN Albumin ≥ 3.0 g/dL Renal Creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault formula. Coagulation PT-INR and APTT within normal limits Exclusion Criteria: Diagnosis of islet neoplasm acinar cell carcinoma, non-adenocarcinoma (i.e., lymphoma, sarcoma), adenocarcinoma originating from the biliary tree, or cystadenocarcinoma. Subjects who have surgically resectable locally advanced pancreatic adenocarcinoma following treatment with FOLFIRINOX. Subject has received prior treatment with Ampligen®. Therapy with investigational drugs within 6 weeks of beginning study medication. History of prior malignancy, except for adequately treated in situ cancer, basal cell, squamous cell skin cancer, or other cancers (e.g., breast, prostate) for which the subject has been disease-free for at least 3 years. Subjects with prior cancer that is adequately controlled per the judgement of the Investigator will not be excluded from the study. Any serious medical condition, laboratory abnormality, psychiatric illness, or comorbidity that, in the judgment of the Investigator, would make the subject inappropriate for the study. Serious systemic fungal, bacterial, viral, or other infection that is not controlled or requires intravenous (IV) treatment for infection(s). Known history of positivity (regardless of immune status) for human immunodeficiency virus (HIV). Known history of, chronic active, or active viral hepatitis A, B, or C infection Clinically significant bleeding within 2 weeks prior to Randomization (e.g., gastrointestinal [GI] bleeding, intracranial hemorrhage). Pregnant or lactating women. Myocardial infarction within the last 6 months prior to Randomization, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or unstable cardiac arrhythmia requiring medication. Subjects with abnormal electrocardiogram (ECG) at baseline QTc interval >470 ms (calculated using both the Bazett's and Fridericia's corrections). Subjects with positive germline BRCA (gBRCA) mutations. Clinically significant ascites defined as requiring ≥ 1 paracentesis every 2 weeks. Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e., larger than what is required for placement of central venous access, percutaneous feeding tube, or biopsy), within 28 days prior to Randomization or anticipated surgery during the study period. Prior history of receiving immune checkpoint inhibitors (anti-CTLA4, anti-PD1, anti-PD- L1). Inability to return for scheduled treatment and assessments.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ampligen / rintatolimod<br>Subjects will receive rintatolimod [intravenous (IV)], up to 400 mg twice weekly until disease progression. | Drug: Rintatolimod<br>* Rintatolimod (poly I : poly C12U)<br>* Other names: poly I : poly C12U;|
| No Intervention: Control Group / No Treatment<br>Subjects will be followed / no treatment until evidence of disease progression. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS is defined as the time, in months, from date of randomization to date of the first documentation of definitive disease progression as per RECIST v1.1 (the initial progressive disease (PD)) or death due to any cause. | Randomization until disease progression, death, or end of study up to 42 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from date of randomization to death due to any cause. | at 1 year | 
| Objective Response Rate (ORR) | ORR is defined as the proportion of subjects who achieve a Complete Response (CR) or Partial Response (PR) as assessed by RECIST v1.1 | Randomization until disease progression, death, or end of study up to 42 months | 
| Duration of Response (DoR) | DoR is defined as the time from the date of the first documentation of objective tumor response (CR or PR) to the date of the first documentation of objective tumor progression or death due to any cause, whichever occurs first. | Randomization until disease progression, death, or end of study up to 42 months |