First Human Trial of pTTL Immunotherapy in Adults with Advanced Stage IV Colorectal Cancer

What this Trial Is About

Researchers are investigating a new immunotherapy called pTTL for adults with advanced stage IV colorectal cancer. This treatment uses a patients own T cells, taken from tumour-draining lymph nodes, which are stimulated in the lab with personalized tumour-specific neoantigens identified by sequencing the patients tumour. The goal is to evaluate the safety and tolerability of pTTL, which is designed to target multiple unique tumour mutations to help the immune system recognize and attack cancer cells more effectively. The study includes three parts Part I involves collecting tumour and lymph node samples, selecting neoantigens, and manufacturing the personalized pTTL product. This process takes about 8 to 12 weeks. Part II includes pre-conditioning chemotherapy with cyclophosphamide and fludarabine, followed by a single intravenous infusion of pTTL, with dose escalation across patient cohorts. Patients receive supportive care and are monitored for 26 weeks after treatment. Part III is a long-term follow-up lasting up to 4.5 years or until death. Participants will undergo biopsies or surgery to obtain tumour tissue and lymph nodes for creating pTTL. They will receive pre-conditioning chemotherapy before pTTL infusion. Researchers will assess safety by monitoring adverse events, focusing on immune-related effects. Additional evaluations include tumour response, progression, survival rates, and long-term outcomes. The entire study involves regular monitoring, clinical assessments, and follow-up visits over several years to understand the therapys impact and safety profile.

A First-In-Human Trial of pTTL in Advanced Colorectal Cancer