BreAK CRC, a first-in-human phase I/II trial of STC-1010, a new allogenic cancer vaccine for advanced or metastatic unresectable colorectal cancer.
Authors: Benoit You, Antoine Italiano, Antoine Hollebecque, Ahmad Awada, Francesco Sclafani, Diego Tosi, Philippe Alexandre Cassier, Eric Christenson, David Tougeron, David Pérol, Corinne Tortorelli, Benoit Pinteur, Lionel Chalus, George Alzeeb, Paul Bravetti, François Ghiringhelli
Journal: Journal of Clinical Oncology (2024)

TPS3635 Background: Colorectal cancer (CRC) is the 3rd most common cancer worldwide. Although immunotherapy was found active in dMMR/MSI-H “hot” CRC, there is an unmet medical need for drugs likely to heat up “cold” tumors, especially for the pMMR/MSS tumors. The STC-1010 is a novel allogenic vaccine based on 2-steps modifications of established CRC cell lines, expressing native tumor specific antigens (TSA) as along with tumor-associated antigens (TAA) whose immunogenicity was increased by haptenization. Preclinical efficacy and safety results of STC-1010 murine surrogate underline the capacity of the vaccine combined with immunostimulant in low dose (cyclophosphamide and GM-CSF) associated or not with the standard of care (SoC) chemotherapy (FOLFOX or FOLFIRI) to decrease tumor volume, improve mice survival and enhance tumor T cell infiltration in different syngeneic models of mice. Ex-vivo STC-1010’s mechanism of action leads to an immune stimulation of dendritic cells and priming of CD8+ T cells inducing a massive apoptosis of CRC cells. Immunogenicity and preclinical data were confirmed using in ovoon chorio-allantoine membrane model with a significant increase of IL-12, IL-2, IFN-gamma expression in TiLs and tumor necrosis. The good safety profile in mice and no CRS harmful effects prompted the launch of the First in Human trial evaluating the STC-1010 for patients with unresectable advanced/metastatic CRC in 1 st (MSS patients) or second-line settings (MSI-H patients). Methods: The dose-escalation phase I will evaluate on 9 to 18 patients the tolerability of two STC-1010’s dose levels (3x10 6 and 6x10 6 vaccine cells) administered intra-dermally on a weekly basis for 8 weeks, followed by 4 boosts, combined with immunostimulants in low dose (oral cyclophosphamide: 50 mg/day, 3 days before vaccine and GM-CSF: 125or 250 µg, co-injected with vaccine), associated to SoC chemotherapy (mFOLFOX6 ± Bevacizumab). The primary endpoint will be the recommended phase 2 dose, while immunogenicity (T cell specific response against vaccine, delayed-Time of Hypersensitivity measurements associated to interferon-gamma dosage) will be evaluated. If no safety issue, a single-arm phase IIA- expansion cohort on 52 MSS patients and a separate cohort of 20 MSI-H patients who have progressed on SoC ICI (immune checkpoint inhibitor) will receive STC-1010 regimen with a primary outcome of rate of 12 months progression-free survival based on RECIST criteria, while the minimal residual disease will be approached by ctDNA analysis. BREAK-CRC is meant to clinically confirm the promising preclinical outcomes obtained on different syngeneic mouse models and ex-vivo assays about the potential major therapeutic impact of STC-1010 on patients with pMMR/MSS and dMMR/MSI-H ICI-resistant unresectable advanced or metastatic colorectal cancers.