A First-In-Human, Phase I/IIa Trial of the Novel T Cell Immunotherapy pTTL in Patients With Advanced Colorectal Cancer
This is an open-label, non-randomised FIH trial investigating the safety and tolerability of a novel ATMP, pTTL, composed of autologous tumour-draining lymph node-derived T cells stimulated in vitro with personalised cancer neoantigens. The neoantigens are selected through a process starting with next generation sequencing (NGS) of tumour material from the patient followed by selection of neoantigenic mutations using an in-house software, PIOR®. Selected neoantigen epitopes are expressed as recombinant proteins, NAG, and used to stimulate T cells to promote neoantigen-specific T cell expansion in vitro in pTTL production. pTTL is thus based on autologous cells stimulated with patient-specific neoantigens. In consequence, every pTTL product is unique and designated for use in one single individual. pTTL will be administered to patients with stage IV colorectal cancer (CRC) as a single intravenous dose.
• Signed informed consent.
• Adult (age ≥18 years).
• Histological or cytological confirmation of CRC.
• Verified metastatic disease (stage IV classification) and have received all possible standard of care therapies, OR further standard of care therapies are currently not considered to be in the patient's best interest, OR toxicity from previous therapy limits the choice of suitable standard of care therapy OR scheduled pause in palliative standard of care therapy as judged by the Investigator.
• Measurable disease according to RECIST1.1.
• Minimum life expectancy of 6 months at primary inclusion and 3 months at pTTL administration.
• Minimum life expectancy of 3 months from the time that the individual pTTL DP is estimated to be available (as per Investigators clinical assessment). 7. ECOG performance status 0 to 1
• Adequate hematopoietic, hepatic and renal function defined as:
∙ Haemoglobin≥ 95 g/L (blood transfusion not less than 21 days prior to screening),
‣ Absolute neutrophil count ≥ 1.0x 109/L, platelets ≥100 x 109/L
‣ Total bilirubin \< 1.5 x ULN (does not apply to patients with Gilberts Syndrome)
‣ AST and ALT ≤ 1.5 x ULN (or ≤ 5 x ULN in the presence of liver metastases)
‣ Serum creatinine ≤ ULN (if serum creatinine is between 1 and 1.5 x ULN, patients may be eligible provided that the calculated GFR is at least 35 mL/min using Cockcroft- Gault method).
‣ Albumin ≥24 g/L
• Patients of childbearing potential or their partners of childbearing potential must be willing to take the appropriate precaution to avoid pregnancy or fathering a child for the duration of Part I and Part II and practice an approved, highly effective method of birth control during treatment and for 6months after receiving pTTL.
• Approved methods of birth control include:
⁃ Combined (oestrogen and progesterone containing) hormonal birth control associated with inhibition of ovulation: oral, intravaginal, transdermal
⁃ Progesterone-only hormonal birth control associated with inhibition ofovulation: oral, injectable, implantable
⁃ Intrauterine device (IUD)or intrauterine hormone-releasing system (IUS)•Bilateral tubal occlusion
⁃ Vasectomised partner
⁃ True sexual abstinence when this is in line with the preferred and usuallifestyle of the patient. Periodic abstinence (e.g., calendar ovulation,symptothermal, post-ovulation methods) is not acceptable
⁃ Able to undergo surgery or biopsy to obtain tumour tissue for neoantigen evaluation and to retrieve RLNs as starting material for pTTL manufacturing
⁃ The area from which the RLNs will be obtained shall not have been exposed to radiotherapy.