A Phase 1, Open-label, Dose-escalation and Dose-expansion 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
A Phase 1, Open-label, Dose-escalation and Dose-expansion 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
This is a phase 1, open-label, multicentric study evaluating the safety, feasibility and efficacy of ODI-2001, a personnalized therapeutic cancer vaccine composed of DNA neoantigen vaccine, Modified Vaccinia virus Ankara (MVA) viral adjuvant and anti-CTLA4 (ipilimumab), in patients with metastatic or locally advanced colorectal or pancreatic cancer. The study includes a dose-escalation phase to determine the maximum tolerated dose (MTD) followed by an expansion phase to evaluate efficacy in terms of progression-free survival
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.
Inclusion criteria for ENROLMENT STEP 2
Second tumoral evaluation shows disease response with the following definition:
Patient eligible for a 6-week chemotherapy break, with the start of maintenance treatment beginning in week 7.
Exclusion Criteria:
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