Erbitux (cetuximab)

P2, N=38, Active, not recruiting, Australasian Gastro-Intestinal Trials Group | Recruiting --> Active, not recruiting | N=90 --> 38 | Trial primary completion date: Apr 2026 --> Jan 2026

P=N/A, N=6, Active, not recruiting, Australasian Gastro-Intestinal Trials Group | Recruiting --> Active, not recruiting | Phase classification: P2 --> PN/A | N=75 --> 6 | Trial completion date: Jun 2025 --> Dec 2027 | Trial primary completion date: Jun 2024 --> Dec 2025

P1, N=30, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

PDC treatment significantly suppresses tumor growth in in vivo KRAS mutant xenograft model, demonstrating superior efficacy compared with cetuximab-based regimens and controls, without observable body weight loss. This strategy uses EGFR as a delivery portal instead of a signaling target, enabling KRAS independent anti-tumor activity. These findings indicate a non-canonical EGFR mediated delivery approach with potential translational relevance for the treatment of therapy resistant CRC.

Treatments include surgery, radiation, and chemotherapy, with ongoing trials investigating agents like cetuximab, cisplatin, and Tazemetostat. Tazemetostat, targeting KMT2D-related DNA (deoxyribonucleic acid) methylation, and cetuximab, targeting the PIK3CA signaling cascade, may offer therapeutic benefits. Further research on mutation-specific therapies could improve treatment strategies.

Outcomes following progression on chemotherapy and MAPK-targeted therapy with Encorafenib plus Cetuximab remain poor, highlighting an unmet need for effective later-line treatments. We discuss the mechanistic framework by which a subset of BRAFV600E-mutant MSS mCRC may respond to immune checkpoint inhibition through an inflamed immune microenvironment driven by constitutive MAPK signalling. This case illustrates the interplay between tumour-agnostic biomarkers such as TMB-high and tumour-specific context, and highlights the value of longitudinal genomic profiling, including ctDNA, to identify resistance mechanisms and guide treatment selection.

Further studies investigating the draining lymph node dendritic cells (DCs) indicate that the destruction of cetuximab-coated tumor cells by G47Δ promotes uptake of tumor cells by DCs, enhances the priming of immune responses, and subsequently stimulates tumor-specific CD8+ T cells. These results suggest that the combination of G47Δ therapy and molecular targeted therapies with ADCC activity may represent a useful therapeutic strategy for enhancing antitumor immune responses, even after the emergence of acquired resistance.

Flow cytometry and Western blot results showed that CTX-p-QM-1h-NLC could effectively inhibit the expression of TrxR and increase the expression of Bax and caspase 3 in vivo, which was consistent with the increase in ROS levels and the induction of apoptosis in 4T1 cells. These results indicated that the construction of CTX-p-QM-1h-NLC is worthy of further investigation.

P1, N=130, Recruiting, Bayer | Not yet recruiting --> Recruiting

P2, N=30, Recruiting, The First Hospital of Jilin University

P=N/A, N=151, Completed, The First Hospital of Jilin University

P2, N=25, Recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Active, not recruiting --> Recruiting