Erbitux (cetuximab)

P1, N=830, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Aug 2027 --> Feb 2030 | Trial primary completion date: Aug 2027 --> Feb 2030

Most national and regional guidelines recommend first-line therapy with an immune checkpoint inhibitor (with or without chemotherapy) or a cetuximab-based regimen, by assessment of expression levels of the biomarker programmed cell death-ligand 1 (PD-L1)...This review highlights the factors that should be considered for treatment decision-making in patients with R/M SCCHN. It also summarizes the current evidence for clinical outcomes based on treatment sequencing and provides guidance on choosing an optimal treatment regimen for patients in the first-line treatment setting and beyond.

P2/3, N=174, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Dec 2024 --> Jun 2025

P1, N=156, Recruiting, Pfizer | Trial completion date: Mar 2028 --> Aug 2028 | Trial primary completion date: Sep 2026 --> Feb 2027

P2, N=67, Recruiting, Gruppo Oncologico del Nord-Ovest

Tumor infiltration by NK cells was confirmed using flow cytometry and immunohistochemistry, highlighting the increased presence of NK cells (CD3- CD56+). These findings suggest that combination allogeneic NK cells and cetuximab could be a potential therapeutic modality for HNSCC and provide a foundation for future clinical trials to improve patient outcomes.

P1, N=24, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

PET with intravenously administered [64Cu]Cu-PCTA-cetuximab demonstrated high precision for diagnosis of SLN metastasis in a xenograft model of EGFR-positive human breast cancer. Although further evaluation is necessary, intradermal/subdermal administration could be a useful therapeutic approach owing to its high accumulation in SLNs.

Recently, fourth-generation AIs, EAI045, have been discovered to potently and selectively inhibit various EGFR mutations but limited antiproliferative effects in the absence of the antibody cetuximab...However, path-independent alchemical approaches like streamlined alchemical free energy perturbation and binding free energy estimator 2 (BFEE2) were employed to validate the results and identify potent compounds. These findings pave the way to identification of novel potential fourth-generation AIs, which require further experimental validation.

This system is successfully applied on A549 cells to capture the interactome of epidermal growth factor receptor (EGFR) using a Cetuximab-Chlorin e6 conjugate...EGFR directed chemoproteomics experiments reveal significant overlap with the carbene system, with the carbene approach capturing a subset of interactions identified by the SOG system. Finally, we deploy our approach for the characterization of EGFR in resected human glioblastoma (GBM) tissue samples removed from distinct locations in the same tumor, representing the tumor's infiltrating edge and its viable center, identifying several GBM specific interacting proteins that may serve as a launch point for future therapeutic campaigns.

P1/2, N=540, Recruiting, Eli Lilly and Company | Trial completion date: Jun 2026 --> Apr 2027 | Trial primary completion date: Jun 2026 --> Apr 2027

Considering a WTP threshold of 7.5 million JPY (approximately 53,700 USD) per QALY, Bmab might be a cost-effective treatment option for patients with KRAS wild-type mCRC in Japan. Further studies on economic evaluations based on personalized drugs and patient selection based on clinical and genetic information are warranted.

P2, N=119, Recruiting, Fudan University

P2, N=65, Not yet recruiting, Grupo Español de Tratamiento de Tumores de Cabeza y Cuello

The median OS for patients treated with the BEACON regimen (encorafenib plus cetuximab, with or without binimetinib) was 13.3 months, which was significantly better than that of patients treated without it (7.2 months; hazard ratio=4.180, 95% confidence interval=1.036-18.631, p=0.029). The BRAF V600E mutation was associated with poor prognosis. The BEACON regimen resulted in improved OS compared with other CRC treatment regimens.

Additionally, membrane expression of hEGFRt facilitated in vivo CAR-T cell elimination after cetuximab administration...Altogether, this study provides a cost-effective, GMP-compliant manufacturing process for the generation of CAR-T cells using non-viral vectors. These results have supported the approval of a clinical trial to evaluate TranspoCART19 cells in patients with relapsed/refractory lymphoma (NCT06378190) that is currently ongoing.

P2, N=21, Recruiting, H. Lee Moffitt Cancer Center and Research Institute

P1/2, N=95, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jan 2025 --> Jun 2025

Furthermore, ST3GAL1 silencing augmented the sensitivity to cetuximab-mediated cell lysis. Our findings provide novel insight into the mechanisms underlying the function of ST3GAL1 in promoting tumor cell migration through the EGFR/NRP1 pathway. Our results suggest that ST3GAL1 may represent a valuable target for strategies aimed at inhibiting tumor migration.

P1/2, N=53, Suspended, University of Chicago | Recruiting --> Suspended

Further, GEN demonstrated efficacy in combinatorial therapy with various standard anticancer agents like 5-FU, cetuximab, cisplatin, clofarabine, doxorubicin, tamoxifen, TRAIL, trastuzumab, and other agents with anticancer activities such as capsaicin, curcumin, daidzein, lycopene, resveratrol, sulforaphane, etc., across a spectrum of cancers including the cancers of bone, brain, breast, cervix, colorectal, endometrium, esophagus, head and neck, leukemia, liver, lung, ovary, pancreas and stomach. Thus, further clinical validation of these potential combinations involving GEN is warranted to confirm the preclinical findings.

P3, N=165, Recruiting, Shanghai Kechow Pharma, Inc. | Not yet recruiting --> Recruiting

NET-derived elastase inactivated PAR2 canonical signaling and promoted phagocytosis by downregulating CD24, which functions as a phagocytotic checkpoint in CRC liver metastasis. Thus, PAR2 inhibitors combined with CTX may serve as a novel therapeutic strategy against advanced CRC.

Finally, novel treatment strategies are available. This review will discuss on currently approved treatments for BRAF V600E mutated mCRC and will try and portray the changing landscape in this setting in the era of targeted molecular therapy.

P2, N=36, Recruiting, Fudan University | Not yet recruiting --> Recruiting

P3, N=1147, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting

P2, N=116, Recruiting, Fudan University

P3, N=460, Recruiting, Centre Leon Berard | Not yet recruiting --> Recruiting

Mass ion pairs were tracked using multiple reaction monitoring (MRM) in positive polarity mode and the precursor to daughter ion transition m/z values for Encorafenib, Cetuximab(peptide), and Tofacitinib (internal reference) are 540.15 → 369.85, 643.34 → 653.31, and 313.17 → 221.05, respectively. It tracks drug levels drugs from administration to several hours post-dose at set intervals, enabling the evaluation of metabolism, excretion, and protein binding, which aid in the creation of treatment plans. It also facilitates routine monitoring of selected medications in clinical trials.

Cetuximab (Ctx), a monoclonal antibody targeting the epidermal growth factor receptor (EGFR) for colorectal cancer treatment, often faces diminished clinical efficacy due to acquired resistance driven by EGFR mutations...Additionally, western blot experiments using HEK-293 T cells showed that the designed CtxD103R effectively inhibits EGF-stimulated phosphorylation of EGFRK489E. Our findings highlight a rational design approach, empowered by interaction landscape at atomic detail, as a promising and cost-effective strategy to combat mutation-driven resistance in antibody therapies.

P3, N=400, Recruiting, Seagen Inc. | Trial completion date: Apr 2028 --> Jul 2029 | Trial primary completion date: Aug 2025 --> Apr 2026

P1/2, N=456, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting

P1/2, N=0, Withdrawn, ImmunityBio, Inc. | Phase classification: P1b/2 --> P1/2

For enhancement of the therapeutic efficiency, a combined targeted radio-photothermal candidate was synthesized by radiolabeling the antibody with Iodine-131. The combinatorial model (Fe3O4@CS-HA-Cet-131I MNCs) exhibited the highest toxicity against HepG2 cells upon NIR irradiation due to the synergistic combined radio- photothermal action.

P1, N=33, Recruiting, The Methodist Hospital Research Institute

The blockage of EGFR/Akt/ERK signalling by cetuximab was re-observed in SW620-R cells after silencing YY1 but impaired in HCT116 by overexpressing YY1. The YY1 mediates the resistance of KRASmut CRC cells to cetuximab.

P1, N=498, Recruiting, Genentech, Inc. | Trial primary completion date: Mar 2025 --> Feb 2026

Inhibiting TGF-β1 diminished cancer cell viability and migration and promoted apoptosis in NSCLC, as confirmed by the findings of this study. Therefore, targeting siTGF-β1 with immunoliposomes may be a new therapeutic strategy for treating non-small-cell lung cancer.

P1/2, N=102, Active, not recruiting, Erasca, Inc. | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Aug 2024 --> Aug 2025

P1, N=200, Active, not recruiting, Erasca, Inc. | Trial completion date: Jul 2025 --> Feb 2026 | Trial primary completion date: May 2025 --> Nov 2025

In addition, the relative potency of the FcIgG-GE11 peptibody compared to Cetuximab was assessed using the MTT results by Slope Ratio Analysis. These findings suggest that FcIgG-GE11 peptibody can provide a specific and efficient tool for both targeting and treating cancer cells.

Most US patients with R/M HNSCC are now receiving CPI-based therapy in the frontline setting; however, PD-L1 testing remains underutilized. "Off-label" use of CPI monotherapy in PD-L1-negative/unknown HNSCC is common, particularly among elderly patients.