Erbitux (cetuximab)

P3, N=204, Recruiting, Sixth Affiliated Hospital, Sun Yat-sen University | Not yet recruiting --> Recruiting

P1/2, N=222, Not yet recruiting, Genfleet Therapeutics (Shanghai) Inc.

P1/2, N=210, Recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | N=96 --> 210 | Trial completion date: Mar 2028 --> Mar 2029 | Not yet recruiting --> Recruiting | Trial primary completion date: Mar 2026 --> Mar 2027

Importantly, combining cetuximab with the GDH1 activity inhibitor R162 curbed tumor metabolic adaptation, reversed TIME remodeling, and suppressed KRAS activation, thereby preventing immune escape and metastatic progression. Our findings unveil the EGFR/GDH1/αKG/ALKBH5 axis as a key modulator of cetuximab response and suggest that post-treatment monitoring of blood αKG may help identify patients who could benefit from GDH1 inhibition to augment immunotherapy and KRAS-targeted strategies.

Patients with high TEPGS exhibited resistance to immunotherapy but responded to a BRAF V600E inhibitor, while TEPGS showed tentative value for predicting cetuximab response and preliminary utility for bevacizumab. Functional assays confirmed ARPC1B as an oncogene. Our findings establish TEPGS as a valuable biomarker for prognostic stratification and tailored therapy selection in CRC.

P1, N=95, Not yet recruiting, National Cancer Institute (NCI)

The EXTREME regimen (platinum, 5-fluorouracil, and cetuximab) was the former first-line standard, but the advent of immune checkpoint inhibitors (ICIs), particularly pembrolizumab based on the KEYNOTE-048 trial, has transformed the treatment landscape. Economic evaluations show cost-effectiveness varies by region. Future directions include novel bispecific agents, triplet regimens, and biomarker-guided patient selection to optimize outcomes in this challenging disease.

P1, N=84, Completed, Dragonboat Biopharmaceutical Company Limited | Unknown status --> Completed

Our findings define a tumor-stroma metabolic cooperation axis in which TGFβ2-driven lipid exchange sustains adaptive cetuximab tolerance in HNSCC. Targeting TGFβ2-mediated stromal reprogramming or FA transfer represents a promising strategy to delay or overcome resistance to EGFR-targeted therapies.

Triplet chemotherapy based on FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) has achieved high response rates and deep tumor shrinkage. In combination with molecularly targeted agents, triplet therapy plus bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, has demonstrated superior efficacy compared with doublet chemotherapy plus bevacizumab. In patients with RAS/BRAF wild-type tumors, combination therapy with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies such as cetuximab and panitumumab has also shown improved survival outcomes, although toxicity remains a major concern...This review outlines the historical development of triplet therapy in mCRC, summarizes the major clinical trials investigating triplet chemotherapy combined with molecularly targeted agents, and discusses direct comparisons between anti-VEGF- and anti-EGFR-based strategies. Particular emphasis is placed on practical considerations for clinical implementation, including toxicity management, dose optimization, and multidisciplinary supportive care.

P1/2, N=29, Active, not recruiting, University of Colorado, Denver | Trial primary completion date: Feb 2030 --> Jun 2026

P2, N=150, Not yet recruiting, Verastem, Inc.