Erbitux (cetuximab)

These preliminary findings suggest that evaluation of in vitro cytotoxicity together with CD107a expression in mCRC patients derived PBMC could be a useful tool to identify early responders after only 8 weeks of treatment with cetuximab plus avelumab. In addition, we aim to further investigate the potential role of CCL5 secreted by peripheral immune cells and its cut-off as a predictive biomarker of mCRC progression in a larger cohort of patients.

Materials and The phase II CAPRI 2-GOIM trial investigates the efficacy and safety of biomarkerdriven, cetuximab-based, sequence of three treatment lines in mCRC... Baseline plasma-based comprehensive genomic profiling is feasible with high concordance with tissue-based analysis. Liquid biopsy allows identification of misdiagnosed RAS/BRAF alterations and the ultra-selection of pts, which could benefit from anti-EGFR therapies. Finally, potentially actionable gene alterations were found in half of the pts.

The LIBImAb Study is a phase III, randomized, openlabel, comparative, multi-center trial to assess the superiority in terms of efficacy of bevacizumab versus cetuximab in combination with FOLFIRI in mCRC pts, RAS/BRAFwt on tumor tissue and RAS/BRAF mutant (RAS/BRAFmut) at liquid biopsy... These data indicate the feasibility of cfDNA-based prospective enrolment in an interventional trial using a test with a rapid TAT for screening of RAS/ BRAF status in plasma. Our preliminary findings also suggest that ctDNA testing might better recapitulate the tumor heterogeneity of mCRC pts thus complementing tissue genomic profiling.

However, whilst targeting EGFR with cetuximab has been approved for the treatment of OSCC, other single-agent inhibitors of the RTKs have shown modest effects in improving survival. In summary, PTPN11 is a promising therapeutic target in OSCC that can be selectively targeted by SHP2 inhibitor such as TNO155. Our findings on the use of mTOR inhibitor, everolimus to overcome resistance to TNO155 are essential to inform on next phases of clinical trials which is warranted for the treatment of OSCC.

Although cetuximab is the sole anti-EGFR approved by the Food and Drug Administration for treating HNC patients.its response rates are modest...Bioinformatic analysis revealed that BCL2low, IL6low and MMP9low HNC biospecimens are enriched with epithelial cell differentiation gene set, and CASP8high cohort is enriched with extrinsic apoptosis. Altogether, this study emphasizes the therapeutic potential of targeting the apoptotic and inflammatory machineries in HNC using EMD37.

P3, N=370, Active, not recruiting, AstraZeneca | Trial completion date: Jun 2024 --> Sep 2025

P1/2, N=74, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Apr 2025 --> Nov 2025

P1, N=195, Recruiting, Chugai Pharmaceutical | Trial completion date: Mar 2025 --> May 2026

P2, N=101, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting

P1, N=750, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting

P2, N=94, Recruiting, Vall d'Hebron Institute of Oncology | Not yet recruiting --> Recruiting

The tumor growth inhibitory rate was 99.36% for dabrafenib, trametinib, and osimertinib; 99.25% for osimertinib plus vemurafenib; 98.92% for osimertinib, encorafenib, and cetuximab; and 62.83% for pemetrexed plus carboplatin. NGS analysis identified major resistance mechanisms following the triple-targeted therapy, including the EGFR-dependent pathway, EGFR and BRAF V600E-dependent pathway, and an off-target mechanism. EGFR/BRAF/MEK triple-targeted therapy is an effective and safe approach for treating EGFR-mutated NSCLC patients resistant to EGFR-TKIs with acquired BRAF V600E mutations.

P2, N=34, Recruiting, National Cancer Institute, Naples | Trial completion date: Sep 2024 --> Sep 2025

Lastly, the drug sensitivity analysis revealed that the BLCA cells in the high-risk group showed an increased sensitivity to cisplatin, sunitinib, cetuximab, axitinib, docetaxel, saracatinib, vinblastine and pazopanib compared with those in the low-risk group. According to the Quantitative real time PCR results, we found that five lncRNAs of the risk model were more highly expressed in BCa cell lines than human immortalized uroepithelial cell line. The disulfidptosis-related lncRNA risk model has a valuable effect in assessing the prognosis of BLCA patients.

P1, N=830, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Aug 2026 --> Aug 2027 | Trial primary completion date: Aug 2026 --> Aug 2027

P1, N=240, Recruiting, Tizona Therapeutics, Inc | Active, not recruiting --> Recruiting | Trial primary completion date: Jun 2024 --> Jun 2027

Our data indicate that targeted therapy using e.g., trastuzumab deruxtecan, bicalutamide, pembrolizumab, cetuximab, entrectinib or sacituzumab govitecan might be a promising option especially for a relevant subset of patients with RM-SGC not suitable for salvage surgery. However, evidence from clinical studies regarding response rates to these therapies remains sparse, which underlines the need of multicenter clinical trials.

P2, N=29, Recruiting, Australasian Gastrointestinal Trials Group | Not yet recruiting --> Recruiting

P1, N=240, Active, not recruiting, Tizona Therapeutics, Inc | Trial completion date: Jun 2024 --> Jun 2027 | Trial primary completion date: Dec 2023 --> Jun 2024

P1/2, N=383, Active, not recruiting, MedImmune LLC | Trial completion date: Sep 2024 --> Sep 2025

Lastly, we showcased the targeted BCP-LNPs using a Cetuximab-conjugated formulation...This finding underscores the potential of BCP-LNPs in targeted gene therapy, especially in challenging scenarios such as tumor targeting. Overall, our study establishes the viability of BCP-LNPs as a versatile, efficient, and targeted delivery platform for nucleic acids, opening avenues for advanced therapeutic applications.

No dose-limiting toxicities (DLTs) were observed; however, one patient experienced Grade 2 cytokine release syndrome (CRS) (table 2), managed with tocilizumab...Ongoing analyses include phenotyping of pre- and post-infusion CBNK cells, donor NK cells, and other immune cell types. Conclusions The combination of cetuximab with pre-A+E CBNK cells is safe and demonstrates promising efficacy for treating MRD in CRC.View this table:View inline View popup Download powerpoint Abstract 1457 Table 1 Patient characteristicsView this table:View inline View popup Download powerpoint Abstract 1457 Table 2 Safety dataView this table:View inline View popup Download powerpoint Abstract 1457 Table 3 ctDNA clearance: ad interim report

Conversely, the excessive expression of HOXB8 reduced the growth suppression in SW48 cells caused by cetuximab by triggering the STAT3 signaling pathway. Conclusively, we conclude that HOXB8 has played an essential role in cetuximab-resistant mCRC and that treating HOXB8 specifically may be a useful treatment approach for certain cetuximab-resistant mCRC patients.

P1/2, N=430, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

P3, N=1000, Not yet recruiting, Janssen Research & Development, LLC

P1, N=422, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Apr 2026 --> Nov 2029 | Trial primary completion date: Sep 2025 --> Aug 2027 | Recruiting --> Active, not recruiting

P3, N=987, Active, not recruiting, Radiation Therapy Oncology Group

The OLNP@CPT-11 surface was modified with an epidermal growth factor receptor (EGFR) antibody Cetuximab (CET), which can actively target the overexpressed EGFR on the U87 glioblastoma cell surface. Furthermore, magnetic guidance of OLNP-CET@CPT-11 to U87 cells can induce cell death exclusively in the magnetically targeted zone. The dual-targeted strategy also provides the best therapeutic efficacy against subcutaneously implanted U87 tumors in nude mice with intravenously delivered OLNP-CET@CPT-11.

No abstract available

In this single-center, prospective, randomized controlled trial, we randomly assigned (1 : 1) patients with locally advanced rectal cancer with wild-type RAS/BRAF gene to two groups: 5 cycles of modified leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin combination regimen (modified FOLFOX6, mFOLFOX6) concurrent with 25 times radiotherapy or 5 cycles of mFOLFOX6 plus cetuximab, all with subsequent total mesorectal excision (TME) resection and adjuvant chemotherapy. Additionally, lower rates of preventive enterostomy and low anterior resection syndrome were shown in the mFOLFOX6-Cet group compared to the mFOLFOX6-RT group. The neoadjuvant treatment strategy of mFOLFOX6 with cetuximab is feasible and promising for patients with locally advanced rectal cancer, even superior to mFOLFOX6 with radiotherapy.

P1/2, N=44, Terminated, Bristol-Myers Squibb | N=308 --> 44 | Trial completion date: May 2025 --> Aug 2024 | Active, not recruiting --> Terminated; The Study has been terminated due to non-safety reasons; business objectives have changed.

Intriguingly, reducing intratumoral DAG by fenofibrate or Pf-06471553 restores the antitumor efficacy of encorafenib/cetuximab on resistant BRAFV600E-mutant mCRC, interrupted PKCα-CRAF-MEK-ERK signaling. These findings reveal the critical metabolite DAG as a modulator of encorafenib/cetuximab efficacy in BRAFV600E-mutant mCRC, suggesting that fenofibrate may prove beneficial for resistant BRAFV600E-mutant mCRC patients.

The safety profile of FAP-IL2v in combination with cetuximab was acceptable and pharmacodynamic markers support the proposed mode-of-action of this combination, but the overall low antitumor activity does not warrant further clinical exploration in HNSCC. [Part C of Study BP29842 (NCT02627274).].

P3, N=355, Not yet recruiting, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

P1, N=156, Recruiting, Pfizer | Trial completion date: Feb 2029 --> Nov 2027 | Trial primary completion date: Aug 2027 --> May 2026

No abstract available

Established therapeutic targets in HNSCC include EGFR (cetuximab) and PD-1 (pembrolizumab and nivolumab). Identification of predictive biomarkers may guide the use of targeted agents and combination therapies. Clinical trials supported by strong preclinical data in relevant models are more likely to advance treatment options.

P2, N=81, Recruiting, Shanghai Institute Of Biological Products | Not yet recruiting --> Recruiting

P1, N=53, Terminated, Pfizer | Trial completion date: Nov 2025 --> Jun 2024 | Active, not recruiting --> Terminated; The study was prematurely discontinued due to strategic reasons, not major safety concerns, futility, or requests from any regulatory authorities

P2, N=70, Not yet recruiting, Groupe Oncologie Radiotherapie Tete et Cou

P1, N=530, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting

P2, N=25, Recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS