Phase II Study of OSE2101 Plus FOLFIRI Versus FOLFIRI Alone as Maintenance Therapy in HLA-A2 Positive Patients with Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma
- Trial ID
- 2024-518139-12-00
- Protocol
- D17-01 PRODIGE 63
- Sponsor
- Gercor
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the **overall survival** (OS) of patients with locally advanced or metastatic **Pancreatic ductal adenocarcinoma** (PDAC) who are HLA-A2 positive and have undergone a 4-month induction chemotherapy with FOLFIRINOX without disease progression. The evaluation focuses on the efficacy of OSE2101 plus FOLFIRI or FOLFIRI alone as maintenance therapy. This is clinically relevant as it aims to determine the potential benefits of these maintenance therapies in prolonging survival in a challenging patient population.
Secondary objectives include:
- To assess the **progression-free survival** (PFS).
- To evaluate the **safety profile** of the treatments.
- To determine the **objective response rate** (ORR).
- To assess health-related **Quality of Life** (HRQoL).
- To evaluate **Q-TWiST** (Quality-Adjusted Time Without Symptoms of Disease or Toxicity of Treatment).
- To identify **predictive markers of response** through biological and imaging assessments.
- To investigate the association between **sarcopenia** and immune-related adverse events (imAEs) in patients treated with OSE2101 alone or with nivolumab, and adverse events in patients treated with chemotherapy.
Participants
The clinical trial involves participants diagnosed with **locally advanced or metastatic Pancreatic ductal adenocarcinoma**. The study population includes both male and female subjects aged 18 years and older, with an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants must have a histologically or cytologically confirmed diagnosis of pancreatic ductal adenocarcinoma and be HLA-A2 positive. The trial does not include a vulnerable population. Participants are required to have stable disease or tumor response following a 4-month induction chemotherapy with FOLFIRINOX, without disease progression. Adequate organ function and a life expectancy of at least 3 months are necessary. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified. Key inclusion criteria include the ability to comply with protocol requirements and registration in a national healthcare system. Exclusion criteria are not detailed in the provided data.
Plans and Procedures
The clinical trial is a **randomized**, non-comparative, phase II study designed to evaluate the efficacy of maintenance therapy with OSE2101 plus FOLFIRI, or FOLFIRI alone, in patients with locally advanced or metastatic **pancreatic ductal adenocarcinoma**. The trial employs a **double-blind** methodology to ensure unbiased results. The primary objective is to assess overall survival (OS) in patients who have undergone a 4-month induction chemotherapy with FOLFIRINOX without disease progression. The trial is expected to conclude by December 30, 2024, with recruitment having commenced on September 20, 2019.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as measurable disease according to RECIST v1.1, adequate organ function, and HLA-A2 genotype. Following successful screening, participants will be randomized to receive either OSE2101 plus FOLFIRI or FOLFIRI alone. Regular follow-up visits will be scheduled to monitor treatment response, adverse events, and overall health status. These visits will include assessments such as CT scans for progression-free survival (PFS) evaluation and quality of life questionnaires. The end-of-study visit will occur after the completion of the treatment period or upon early termination.
The expected length of participant involvement is up to 24 months, contingent upon individual response and tolerance to the treatment. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. The trial will also monitor secondary endpoints, including toxicity profiles, response rates, and potential predictive biomarkers. The study is conducted under strict adherence to ethical guidelines, ensuring the safety and well-being of all participants throughout the trial duration.
Treatment
The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. **ELVORINE** 100 mg/10 mL, a **solution for injection**, is utilized as an auxiliary treatment. The active substance in ELVORINE is **levoleucovorin**, a chemically derived compound. The medication is administered via **infusion** with a maximum daily dose of 180 mg/m² and a total maximum dose of 19,200 mg/m² over a treatment period of 24 weeks. The pharmaceutical form is a solution injectable, and it is produced by Pfizer Holding France.
**TEDOPI** is the experimental treatment in this trial, formulated as an **emulsion for injection**. It contains a combination of 10 synthetically manufactured peptides, including MPS-112, MPS-106, MPS-213, and others. The product is preservative-free and sterile, designed for injection. The maximum daily dose is 1.0 mL, with a total maximum dose of 14 mL over a 24-week period. TEDOPI is developed by OSE Immunotherapeutics and is administered via injection.
**FLUOROURACILE PFIZER** 50 mg/mL is another auxiliary treatment, provided as a **solution for infusion**. The active substance is **fluorouracil**, a chemical compound. The administration route is infusion, with a maximum daily dose of 2800 mg/m² and a total maximum dose of 134,400 mg/m² over the course of 24 weeks. This product is manufactured by Pfizer Holding France.
**IRINOTECAN VIATRIS** 20 mg/mL is also used as an auxiliary treatment, available as a **concentrate for solution for infusion**. The active ingredient is **irinotecan hydrochloride trihydrate**, a chemical substance. The medication is administered via infusion, with a maximum daily dose of 180 mg/m² and a total maximum dose of 8640 mg/m² over a 24-week period. This product is produced by Viatris Sante.
Efficacy
The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is the overall survival (OS) rate at 12 months. Evaluable patients for OS will include those alive at 12 months and those who have died within 12 months. Patients lost to follow-up before 12 months without confirmation of death will be considered non-evaluable. OS is defined as the time from randomization to death from any cause, with survival time censored at the date of the last clinical assessment in the absence of death confirmation.
Secondary endpoints include progression-free survival (PFS) assessed by centralized review of CT-scan imaging, response according to RECIST v1.1 criteria, and health-related quality of life (HRQoL) measured by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. Additionally, the study will evaluate all grade and severe (grade 3-5) toxicities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, Q-TWiST, potential predictive biomarkers from blood and tumor tissue, and immune-related adverse events (imAEs) in relation to **sarcopenia**.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed and dated informed consent document, willing and able to comply with protocol requirements
- Adequate organ function, as defined by the following: - Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) - Total serum bilirubin < 1.5 ULN - Prothrombin ratio > 70% - Serum albumin ≥ 2.8 g/dL - Hemoglobin ≥ 10,0 g/dl - White blood cell count (WBC) ≥ 3,000/μL - Absolute neutrophil count (ANC) ≥ 1,500/μL - Platelets ≥ 100,000/μL - Serum creatinine ≤ 1.5 ULN or creatinine clearance > 50 mL/min (MDRD)
- Life expectancy ≥ 3 months
- Women participants of childbearing potential must have a negative serum pregnancy test within the 3 days prior to the first treatment administration until 180 days after the last dose of FOLFIRI, and after the last dose of OSE2101 for women and 90 days after the last dose of OSE2101 for men. Both women participants of childbearing potential and men participants who are sexually active with women of childbearing potential must agree to use a reliable method of birth control (i.e. pregnancy rate < 1% per year);
- Registration in a national health care system (PUMA included)
- Histologically or cytologically proven PDAC
- Age ≥ 18 years
- ECOG Performance Status (PS) 0-1
- HLA-A2 genotype
- Recurrent or advanced disease not amenable to surgery with curative intent (previous resection of primary tumor allowed)
- Measurable or evaluable (radiologically detectable disease which does not fulfill RECIST criteria for measurable disease) lesions according to RECIST v1.1 criteria (CT-scan < 4 weeks)
- Stable disease or tumor response according to RECIST v1.1 after a 4-month (8 cycles, CT-scan at C8 ± 2 weeks) course of first-line FOLFIRINOX or modified FOLFIRINOX induction chemotherapy
- Have archival tissue sample that has been identified and confirmed as available for study, or newly obtained core or excisional biopsy of a tumor lesion
Exclusion Criteria
- Obstructive jaundice (bilirubin > 1.5 ULN) without adequate biliary drainage
- Any systemic steroid therapy (> 10 mg daily dose of prednisone or equivalent) for more than seven days one month before inclusion
- Allograft recipient
- Active HBV, HCV, or HIV infection
- Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri
- Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of neuropathy, alopecia, and the laboratory values defined in the inclusion criteria
- Known active central nervous system metastases and/or carcinomatous meningitis; patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids at a dose > 10 mg/day of prednisone or equivalent for at least 14 days prior to trial treatment
- Uncontrolled massive pleural effusion or massive ascites
- History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, that has required systemic treatment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
- Evidence of interstitial lung disease, any active, non-infectious pneumonitis, or known active tuberculosis
- Active uncontrolled infection, or current unstable or uncompensated respiratory or cardiac conditions, or bleeding
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
- Live vaccine administration within 30 days prior to the first dose of study treatment
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the participant, in the opinion of the treating investigator
- Known or suspected drug hypersensitivity to OSE2101 vaccine
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational product
- Treatment with any investigational medicinal product within 28 days prior to study entry
- Prior intolerance/severe toxicity with 5FU or irinotecan (including DPD and UGT1A1 deficiency)
- Pregnancy/lactation
- Tutelage or guardianship
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Yet Recruiting | 20 Sept 2019 | 106 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ELVORINE 100 mg/10 mL, solution injectable | Other | SOLUTION INJECTABLE | INFUSION | 180 | 24 | PRD422519 |
TEDOPI | Test | EMULSION FOR INJECTION | INJECTION | 1.0 | 24 | PRD11292393 |
FLUOROURACILE PFIZER 50 mg/mL, solution à diluer pour perfusion | Other | SOLUTION À DILUER POUR PERFUSION | INFUSION | 2800 | 24 | PRD422372 |
IRINOTECAN VIATRIS 20 mg/ml, solution à diluer pour perfusion | Other | SOLUTION À DILUER POUR PERFUSION | INFUSION | 180 | 24 | PRD10036294 |