Study Evaluating the Safety Feasibility and Efficacy of ODI-2001 Vaccine, a Personnalized Immunotherapy in Patients With Metastatic or Locally Advanced Colon Cancer or Pancreatic Cancer

Inclusion criteria

• Patient capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Male or female of > 18 years of age
• Histologically confirmed diagnosis of metastatic or locally advanced solid tumour: • Colorectal carcinoma with MicroSatellite Stable colorectal carcinoma (MSS) not eligible for surgery or other ablative therapies. • Pancreatic adenocarcinoma not eligible for surgery or other ablative therapies.
• ECOG performance status 0 or 1
• Baseline Tumoral evaluation (thoraco-abdomino-pelvic computed tomography) performed before the initiation of the standard first line-chemotherapy with at least one measurable lesion according to RECIST 1.1 criteria that can be accurately assessed at baseline and is suitable for repeated assessment.
• Eligible to start a standard first line chemotherapy indicated in colorectal cancer (FOLFOX/FOLFIRI/FOLFIRINOX or FOLFOXIRI +/- anti-VEGF/EGF) pancreatic cancer (FOLFIRINOX/NabPaclitaxel-Gemcitabine).
• Adequate haematological, renal and hepatic laboratory requirements : • Haemoglobin > 9.0 g/dL • White Blood Cells (WBC) > 2.5x109/L including, absolute neutrophils count (ANC) > 1.5x109/L, total lymphocytes count > 0.5x109/L • Platelet's count > 100x109/L• Serum alkaline phosphatase (PAL) ≤ 3 x ULN in the absence of liver or bone metastases and ≤ 5 x ULN in patients with documented bone or liver metastases• Serum transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN in the absence of liver metastases and ≤ 5 x ULN in case of liver metastases

• Total bilirubin ≤ 1.5 x ULN• Albumin ≥ 30 g/L • Glomerular Filtration Rate ≥ 50 mL/min (according to Modification of the Diet in Renal Disease [MDRD] formula or Cockroft & Gault formula)
• Adequate cardiac function with QTc < 450 msec on baseline ECG, using the Fridericia correction cQTcF formula
• Life expectancy of at least 6 months
• Patient willing and able to comply with scheduled visits and exams during the follow-up and treatment compliance of the protocol, for the duration of the study including : • mandatory blood sampling (3 blood sampling) • mandatory biopsy of the tumor following enrolment in STEP 1 if no archived material dated less than 2 years is available in sufficient quality or quantity and a mandatory biopsy at 2 months after the initiation of ODI-2001 vaccine administration.
• Men who are sexually active with women of childbearing potential must agree to use contraceptive method during the ODI-2001 treatment period and for at least 4 months after the last ODI-2001 administration. The individual methods of contraception may be determined in consultation with the investigator and it must have a failure rate of less than 1% per year.
• A female participant is eligible to participate if she is not pregnant (negative urinary or serum pregnancy test), not breastfeeding, and at least one of the following conditions applies: • Not a woman of childbearing potential OR • Women of childbearing potential who agrees to apply effective contraception method during the treatment period and for at least 4 months after the last dose of study treatment. Effective contraception methods include a combination of any of the following (unless method is abstinence or sterilization, in which only one method is required): - Use of oral, injected, or implanted hormonal methods of contraception, or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%). In case of use of oral contraception, women should have been stable on the same pill for a minimum of 6 months before taking study treatment. - Placement of an intrauterine device or intrauterine system. - Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository. - Total abstinence - Female sterilization at least eight weeks before taking study treatment. - Male sterilization (at least six months prior to screening)
• Patient must be affiliated to a social health insurance regimen

Inclusion criteria

for ENROLMENT STEP 1 :

First tumoral evaluation shows disease response with the following definition:

• Colorectal carcinoma: A decrease of at least 30% or more in the sum of the diameters of target lesions compared to the initial sum of diameters (Baseline assessment) = at least partial response definition according to RECIST 1.1 definition.
• Pancreatic carcinoma: A decrease of at least 20% or more in the sum of the diameters of target lesions compared to the initial sum of diameters (Baseline assessment) = adaptative RECIST 1.1 definition.

• Availability of tumoral material in sufficient quality and quantity in FFPE to performed dB209 manufacturing (5-10 slides according to tissue surface area) + tumoral microenvironment assessment (10 slides). In case of lack of tumoral material to performed the mandatory 2 analysis, a new biopsy should be organized.

Inclusion criteria

for ENROLMENT STEP 2

• Second tumoral evaluation shows disease response with the following definition:

• Colorectal carcinoma: A decrease of at least 30% or more in the sum of the diameters of target lesions compared to the initial sum of diameters (Baseline assessment) = at least partial response definition according to RECIST 1.1 definition.
• Pancreatic carcinoma: A decrease of at least 20% or more in the sum of the diameters of target lesions compared to the initial sum of diameters (Baseline assessment) = adaptative RECIST 1.1 definition.
• Patient eligible for a 6-week chemotherapy break, with the start of maintenance treatment beginning in week 7.

Exclusion criteria

• Patients with >10% hepatic involvement as per investigator
• Exposure to any investigational agent within 30 days of enrolment.
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• History of any second malignancy within 2 years with the exception of malignancies with a negligible risk of metastasis or death (e.g. adequately treated carcinoma-in situ of the breast or the cervix, melanoma-in-situ, prostate cancer with Gleason grade ≤6 and prostate specific antigen within normal range).
• Known or suspected history of immunosuppression (severe auto-immune or immunodeficiency disease) including history of invasive opportunistic infections (e.g tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis, aspergillosis) despite infection resolution. Presence or suspicion of active bacterial, fungal or viral infections, or uncontrolled fever
• Patients with major surgery within 4 weeks from enrolment
• Previous vaccination (either therapeutic and/or prophylactic) against cancer
• Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, ototoxicity, vitiligo, and the laboratory values defined in the inclusion criteria.
• Patients under chronic treatment with systemic corticoids or other immunosuppressive drugs (e.g., cyclosporine) unless used at dose levels that are not immunosuppressive (e.g. Prednisone at 10 mg/day or less or as inhaled steroid at doses used for the treatment of asthma) up to 14 days before pre-enrolment.
• Is receiving growth factors including, but not limited to, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 4 weeks from enrolment
• Known history of Positive serology for Human Immunodeficiency Virus (HIV) or Hepatitis C Virus (HCV); presence of HBs antigen in the serum
• History of severe auto-immune or immunodeficiency disease
• Known allergy to any of the components of ODI-2001 (e.g. egg or gentamycin)
• Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty
• Planned to receive yellow fever or other live (attenuated) vaccines during the course of the study
• Recent or active clinically significant infection requiring therapy at the time of first dose
• Any persistent or unresolved drug-related toxicity following previous treatment
• Myocardial infarction or stroke within previous 6 months, unstable angina, serious uncontrolled cardiac arrhythmia, history of myocarditis, or congestive heart failure
• Known symptomatic malignant brain lesion
• Patients with any serious uncontrolled disease or psychiatric condition that, in the opinion of the Investigator, might interfere with the patient's participation in the trial or interfere with the interpretation of trial results