This protocol describes NEOGAP-CRC-01, a first-in-human phase I/IIa clinical trial evaluating autologous personalized tumour-trained lymphocytes (pTTL) in patients with Stage IV colorectal cancer (CRC). Adoptive T cell therapy is presented as a promising alternative to conventional therapies for certain solid tumours. The pTTL approach uses T cells harvested from tumour-draining regional lymph nodes (RLNs) and trained ex vivo to target patient-specific neoantigens derived from tumour-specific mutations. The study aims primarily to assess safety, with secondary objectives that include measures of antitumour activity and exploration of biomarkers.
Manufacturing of pTTL begins with identification of tumour-specific neoantigen-forming mutations using next-generation sequencing of paired tumour and blood samples. Candidate neoantigens are prioritized using the bioinformatics software PIOR®. The selected neoantigen epitopes are recombinantly produced and conjugated to paramagnetic micro-particles using EpiTCer® technology. These recombinantly produced, epitope-bearing micro-particles form the tumour-selective stimulus TC0301, which is used to stimulate and expand RLN-derived T cells in vitro, generating the pTTL product. The resulting pTTL are autologous T cells trained to recognize chosen neoantigen epitopes without genetic modification.
The trial is structured in three sequential parts. Part I covers laboratory and manufacturing activities: sequencing of tumour and blood samples, collection of RLNs, production of TC0301, and pTTL manufacture. Part II encompasses clinical intervention: patient preconditioning, single-dose administration of pTTL, and a 26-week post-treatment follow-up period focused on safety and initial efficacy assessments. Part III extends clinical observation, comprising follow-up for up to five years after pTTL administration to capture longer-term outcomes and late events.
The protocol allows inclusion of up to 16 patients with Stage IV colorectal cancer. pTTL is administered as a single-dose intravenous infusion. The full manufacturing yield will be given within predefined cell-count limits: between 20 × 10^6 and 1 × 10^9 cells. The exact cell yield per patient depends on individual RLN harvest and in vitro expansion during manufacturing.
Prior to infusion, patients receive lymphodepleting preconditioning with cyclophosphamide and fludarabine. After preconditioning, the single pTTL infusion is administered; the trial specifies that the entire product yield—subject to the stated cell-count boundaries—will be infused as one dose. The protocol includes a 26-week clinical follow-up period in Part II and extended monitoring in Part III up to five years.
The primary endpoint of the study is safety. Secondary endpoints include objective treatment response, overall survival (OS), and progression-free survival (PFS). In addition to clinical efficacy and survival measures, the protocol plans assessment of biomarkers related to pTTL persistence, product characteristics, and correlations with treatment response. The document notes that evaluating efficacy may be complex given the highly personalized nature of the product and tumour heterogeneity in CRC.
Safety is the principal focus of the trial. Part II specifies close monitoring during the 26 weeks following infusion to capture adverse events, tolerability, and early signals of activity. Part III extends long-term follow-up to five years to detect late toxicities, durable responses, and survival outcomes. The protocol indicates standard procedures for adverse event reporting consistent with regulatory authorization.
Planned biomarker analyses include tracking pTTL persistence and evaluating product characteristics that may relate to clinical outcomes. Neoantigen identification and selection by PIOR®, combined with epitope delivery via EpiTCer®-based TC0301, are central to the individualized manufacturing workflow and to exploratory correlative studies intended to link product features and patient responses.
The trial is authorized under the Clinical Trial Regulation (Regulation EU No 536/2014) with EU CT number #2024-512296-13-00 and is registered on ClinicalTrials.gov as NCT05908643. The published protocol discloses conflicts of interest: several authors receive research funding from Neogap Therapeutics AB, and some authors are employed by Neogap Therapeutics AB. The source document states these declarations and affirms adherence to data-sharing policies.
Note: This rewritten summary and protocol description are restricted to the details reported in the cited source. No additional efficacy, safety outcomes, or operational details beyond those reported in the source are provided here.