Erbitux (cetuximab)

P2, N=71, Recruiting, University of Wisconsin, Madison | N=110 --> 71

Eight drugs have been approved by the FDA for HNC, including both generic and commercial forms: bleomycin sulfate, cetuximab (Erbitux), docetaxel (Taxotere), hydroxyurea (Hydrea), pembrolizumab (Keytruda), loqtorzi (Toripalimab-tpzi), methotrexate sodium (Trexall), and nivolumab (Opdivo). The most common drugs to treat HPV-associated OPC under these clinical trials and implemented as well for HPV-negative HNC include cisplatin, nivolumab, cetuximab, paclitaxel, pembrolizumab, 5-fluorouracil, and docetaxel...In this context, we identified most mutated genes found in HPV-associated OPC that can represent potential targets for drug development. These include TP53, PIK3CA, PTEN, NOTCH1, RB1, FAT1, FBXW7, HRAS, KRAS, and CDKN2A.

P1, N=830, Recruiting, Merck Sharp & Dohme LLC | N=450 --> 830

P2, N=46, Recruiting, Fulgent Pharma LLC. | Not yet recruiting --> Recruiting

P2, N=33, Not yet recruiting, M.D. Anderson Cancer Center

P1, N=45, Recruiting, Boehringer Ingelheim | Active, not recruiting --> Recruiting | Trial primary completion date: Aug 2024 --> Apr 2025

Patients received anti-EGFR rechallenge therapy, including cetuximab plus avelumab, trifluridine-tipiracil plus panitumumab, irinotecan plus cetuximab, or panitumumab monotherapy. Within the limitation of a subgroup analysis, the absence of liver metastases was associated with significant improved survival. ClinicalTrials.gov Identifiers: NCT02296203; NCT04561336; NCT03227926; NCT05468892.

Our novel treatment strategy delivered acceptable survival outcomes and reduced severe dermatologic toxicities.

According to the results of our real-life data study, there is no significant difference in efficiency between the combination of biological agent and chemotherapy used in the second-line treatments.

P1/2, N=822, Recruiting, Mirati Therapeutics Inc. | Trial completion date: Sep 2024 --> Jan 2026 | Trial primary completion date: Dec 2023 --> Jul 2025

P1, N=42, Not yet recruiting, M.D. Anderson Cancer Center

P2, N=30, Recruiting, Wake Forest University Health Sciences | Trial completion date: Aug 2024 --> Jan 2025 | Trial primary completion date: Mar 2024 --> Sep 2024

Adagrasib plus cetuximab demonstrates promising clinical activity and tolerable safety in heavily pretreated patients with unresectable or metastatic KRASG12C-mutated colorectal cancer. These data support a potential new standard of care and highlight the significance of testing and identification of KRASG12C mutations in patients with colorectal cancer.

P1/2, N=456, Recruiting, Sanofi | Trial completion date: Apr 2027 --> Nov 2026 | Trial primary completion date: Apr 2027 --> Nov 2026

P1/2, N=23, Active, not recruiting, National Cancer Institute (NCI)

P1, N=53, Active, not recruiting, Pfizer | N=36 --> 53

P1/2, N=352, Recruiting, D3 Bio (Wuxi) Co., Ltd | Phase classification: P1 --> P1/2 | N=168 --> 352 | Trial completion date: May 2025 --> Sep 2026 | Trial primary completion date: May 2025 --> Sep 2026

P1/2, N=107, Completed, NuCana plc | Recruiting --> Completed | N=225 --> 107 | Trial completion date: Nov 2023 --> Mar 2024 | Trial primary completion date: Nov 2023 --> Mar 2024

P1/2, N=410, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting | Trial completion date: Jul 2029 --> May 2024 | Trial primary completion date: Aug 2027 --> May 2024

Moreover, the phase III CodeBreaK 300 trial demonstrates the superiority of sotorasib-panitumumab over trifluridine/tipiracil, establishing a new standard of care for patients with colorectal cancer harboring KRAS G12C mutations. Other combinations such as adagrasib-cetuximab, divarasib-cetuximab, or FOLFIRI-panitumumab-sotorasib have also shown a meaningful response rate and are currently under evaluation...In this setting, liquid biopsy emerges as a critical tool to characterize the mechanisms of resistance, consisting mainly of acquired genomic alterations in the MAPK and PI3K pathways and tyrosine kinase receptor alterations, but gene fusions, histological changes, or conformational changes in the kinase have also been described. In this paper, we review the development of KRAS G12C inhibitors in colorectal cancer as well as the main mechanisms of resistance.

In HPV-negative HNSCC, CDK4/6 inhibitor shows promising anti-tumor effects, which exhibits a synergistic effect when combined with EGFR inhibitor only in specific drug concentration and mouse model.

This study indicates that cetuximab-containing second-line chemotherapy can improve outcomes in R/M HNSCC, even after first-line therapy failure or intolerance.

EGFR-Erbitux receptor targeted EnGeneIC Dream Vector with mitoxantrone can be safely delivered in paediatric patients aged 2-21 years with solid or CNS tumours harbouring EGFR expression. The discovery of EGFR expression in a high proportion of paediatric gliomas means that EGFR may be useful as a target for other treatment strategies. Targeted therapeutic-loaded EDVs may be worth exploring further for their role in stimulating an anti-tumour immune response.

Our study investigated the non-genetic resistance mechanisms that colorectal cancer cells develop against cetuximab and the resulting ADCC pressure...The model predicted that intermittent dosing strategy outperforms continuous regimen in delaying treatment resistance. Our findings have implications for improving efficacy and circumventing resistance to targeted antibody therapies.

P1, N=610, Not yet recruiting, Hansoh BioMedical R&D Company

P2, N=46, Recruiting, Gruppo Oncologico del Nord-Ovest

P1, N=47, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting

Subsequently, in vitro investigation indicated that anti-ENO1 antibody, metformin combined with cisplatin/cetuximab could simultaneously target ALDH+ and CD44+ subpopulations. The study preliminarily revealed anti-ENO1 antibody combined with metformin could overcome drug resistance against CSCs by inhibiting the Wnt//β-catenin pathway and might serve as a potential precursor platform for screening ADC. More importantly, it is reasonably believed that antibody-based drug combination therapy might function as an encouraging tool for oncotherapy.

P2, N=34, Recruiting, National Cancer Institute, Naples | Trial completion date: Jan 2024 --> May 2024 | Trial primary completion date: Jan 2024 --> May 2023

Here, we reported two cases with NSCLC who initially harbored an EGFR-sensitive mutation and were both treated with osimertinib, a third-generation TKI. Our findings suggested that a combined regimen of brigatinib and cetuximab could serve as a potentially life-saving therapeutic strategy for critically ill patients with NSCLC, particularly those demonstrating EGFR p.C797S-mediated resistance. Further studies, however, are required to validate and expand upon these promising findings.

P1, N=27, Recruiting, M.D. Anderson Cancer Center | Suspended --> Recruiting

AECs carrying epitopes genetically fused at the N-terminus of the light chains of cetuximab and trastuzumab demonstrate an even more efficient delivery of the T-cell epitopes compared to AECs with the epitope fused to the C-terminus of the heavy chain. We hypothesize that this facilitates more efficient epitope delivery. These findings not only provide additional insights into the mechanism of action of AECs but also broaden the possibilities for genetically fused AECs as an avenue for the redirection of multiple virus-specific T cells toward tumors.

P1/2, N=95, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Mar 2024 --> Aug 2024

P=N/A, N=50, Recruiting, Qilu Hospital of Shandong University

P3, N=400, Recruiting, Massachusetts General Hospital | Trial completion date: Apr 2026 --> Dec 2027 | Trial primary completion date: Apr 2025 --> Dec 2026

P1/2, N=24, Recruiting, Sun Yat-sen University | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=33, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Mar 2024 --> Mar 2026 | Trial primary completion date: Mar 2024 --> Mar 2026

P2, N=198, Recruiting, Sun Yat-sen University | Active, not recruiting --> Recruiting

P2, N=60, Recruiting, Beijing Hospital

Resistant gene mutations caused by anti-EGFR drugs in RAS/BRAF wild-type mCRC patients can be observed by dynamic ctDNA analysis. TP53 and AMER1 mutations, tumor mutational burden (TMB) levels, and TP53/AMER1 co-mutation may predict the efficacy of the first-line cetuximab-contained treatment. Situations of genetic mutations were differentiated from first-line PD to second-line PD, which indicated that mutation detection may contribute to predict prognosis of mCRC patients.

The neoadjuvant regimens were cisplatin and docetaxel (n = 1); carboplatin and docetaxel (n = 1); paclitaxel and cetuximab (n = 1); carboplatin, paclitaxel, and cetuximab (EGFR inhibitor) (n = 2); cisplatin, docetaxel, and pembrolizumab (anti-PD-1 immunotherapy) (n = 1); and carboplatin, paclitaxel, and pembrolizumab (n = 1). One patient had nodal metastasis treated with lymph node dissection and adjuvant chemoradiation. Neoadjuvant systemic therapy can shrink tumors in patients with locally advanced primary lacrimal sac/NLD carcinoma with orbital or skull base invasion.

P2, N=25, Recruiting, Glenn J. Hanna | Not yet recruiting --> Recruiting