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

Official Summary

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

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 77 participants

Study Arms

• Level 1 - Ipilimumab (Anti-CTLA4): 2.5 mg (EXPERIMENTAL)
  Participants recevront la dose de départ : DNA vaccine 4 mg, MVA 10⁷ pfu, Ipilimumab 2.5 mg (Anti-CTLA4). This arm may be expanded in Phase II if dose is selected as RP2D (Recommended Phase 2 Dose)
• Level 2 - Ipilimumab 5 mg (EXPERIMENTAL)
  Participants recevront DNA vaccine 4 mg, MVA 10⁷ pfu, Ipilimumab 5 mg (Anti-CTLA4).This arm may be expanded in Phase II if dose is selected as RP2D (Recommended Phase 2 Dose)
• Level 3 - Ipilimumab 10 mg (EXPERIMENTAL)
  Participants recevront DNA vaccine 4 mg, MVA 10⁷ pfu, Ipilimumab 10 mg (Anti-CTLA4). This arm may be expanded in Phase II if dose is selected as RP2D (Recommended Phase 2 Dose)

Interventions

• BIOLOGICAL: Personalized cancer vaccine including : DNA neoantigen vaccine, MVA viral vector and Ipilimumab (anti-CTLA4) — Participants receive a combination therapy including DNA vaccine 4 mg IM, MVA 10⁷ pfu, and Ipilimumab IV at the dose assigned per arm: 2.5 mg, 5 mg, or 10 mg. Dose escalation is done sequentially in Phase I. The selected dose (RP2D) will be used in Phase II expansion.

Primary Outcomes

• Phase 1 : Maximum Tolerated Dose (MTD) based on Dose Limiting Toxicity (DLT) (28 days) of ODI-2001 Phase 2 : Progression-Free Survival (PFS) (Phase 1 : within 28 days following the first administration of ODI-2001 Phase 2 : Up to 14 months for colorectal cancer cohort and up to 10 months for pancreatic cancer cohort following initiation of chemotherapy.)

Eligibility Criteria

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 perfor

Trial Locations

• CHRU Jean Minjoz, Besançon, France
• Centre Georges-François Leclerc, Dijon, France

Contact Information

• François FG GHIRINGHELLI, Pr — CONTACT
  Phone: 03 45 34 75 38
  Email: fghiringhelli@cgfl.fr
• Emilie ER REDERSTORFF, Project Manager — CONTACT
  Phone: 03 45 34 81 16
  Email: erederstorff@cgfl.fr

Study Officials

• Jean-Marc JML LIMACHER, Dr — STUDY_CHAIR
  Odimma Therapeutics

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