Vectibix (panitumumab)

TRIPLETE is a phase III trial where 435 pts with RAS/BRAF wt – per local assessment – mCRC were randomized to receive first-line FOLFOX/ panitumumab (pan) or mFOLFOXIRI/pan... In contrast to previous data, negative hyperselection both through tissue and plasma analysis failed to demonstrate a prognostic role among pMMR RAS/BRAF wt mCRC pts treated with first-line chemotherapy plus pan. The confounding effect of the associated chemotherapy is a potential explanation for this finding. Tissue and plasma analyses at baseline failed to provide fully concordant results.

P3, N=700, Recruiting, IFOM ETS - The AIRC Institute of Molecular Oncology | Not yet recruiting --> Recruiting

No abstract available

P3, N=450, Recruiting, Amgen | Trial completion date: Jan 2031 --> Apr 2031 | Trial primary completion date: Jun 2027 --> Sep 2027

P1, N=1200, Recruiting, Amgen | Trial completion date: Jun 2029 --> Mar 2028 | Trial primary completion date: Jan 2027 --> Apr 2026

P1, N=1200, Recruiting, Amgen | Trial completion date: Mar 2028 --> Jun 2029 | Trial primary completion date: Sep 2025 --> Jan 2027

[64Cu]Cu-NOTA-panitumumab was successfully used for immuno-PET imaging of EGFR-expressing subcutaneous and metastatic NSCLC tumors. This result represents the basis for developing radiotheranostics for targeting EGFR in cancers and for selecting the right patients for the right treatment at the right time.

An engineered IgA2 antibody specific for the epidermal growth factor receptor (EGFR) demonstrated superior efficacy in activating neutrophils for ADCC compared to Panitumumab using healthy and patient-derived neutrophils, underscoring the potential of the IgA isotype as a therapeutic alternative. The distinct behavior and antibody-isotype dependent ADCC competence of CD177+/- neutrophils of healthy but not HNSCC donors warrants further exploration. Our study emphasizes the importance of personalized immunotherapy treatments that consider the characteristics of neutrophils, patient demographics, and the type of antibody to improve ADCC and ultimately enhance treatment outcomes for HNSCC.

P=N/A, N=757, Recruiting, Takeda | Trial completion date: Jul 2024 --> Jul 2027 | Trial primary completion date: Jul 2024 --> Jul 2027

P2, N=73, Not yet recruiting, UNICANCER | Trial completion date: Jun 2028 --> Oct 2028 | Initiation date: Jun 2024 --> Oct 2024 | Trial primary completion date: Jun 2026 --> Oct 2026

P2, N=126, Ongoing, Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD)

DKC often develops into various tumors in the digestive system at an early age; therefore, appropriate surveillance may be required. In addition, considering that cancers in patients with DKC occur at a young age, fertility preservation and survivorship are also important, and adequate explanations and care should be provided to patients before and after treatment.

P1/2, N=29, Completed, Vanderbilt-Ingram Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Dec 2023

P2, N=60, Recruiting, Al-Azhar University

Age <65 years and anemia were identified as independent baseline risk factors. Additionally, combination prophylaxis was found to be a preventive factor against anti-EGFR monoclonal antibody-induced grade ≥2 overall skin toxicities in patients with liver metastatic CRC.

To overcome this resistance mechanism, various combinations of epithelial growth factor receptor (EGFR) and KRAS G12C inhibitors, including panitumumab plus sotorasib, have been investigated in clinical trials. Based on these results, phase III clinical trials are being conducted to investigate EGFR and KRAS G12C inhibitor combinations as a first or second-line treatment for KRAS G12C mutated advanced CRC. Furthermore, other KRAS G12C inhibitors, KRAS G12D inhibitors, and pan-RAS inhibitors are being developed, which could make more patients with advanced CRC eligible for KRAS inhibition.

P1, N=30, Terminated, Biosplice Therapeutics, Inc. | Phase classification: P1b --> P1 | Active, not recruiting --> Terminated; Study was terminated due business reasons by Sponsor.

P1/2, N=177, Completed, NantBioScience, Inc. | Phase classification: P1b/2 --> P1/2

P3, N=450, Recruiting, Amgen | Not yet recruiting --> Recruiting

This case offers novel insights into the clinical behaviors of BRAF non-V600E-mCRC, potentially advancing personalized therapy for rare and aggressive cases.

P1, N=1200, Recruiting, Amgen | Trial primary completion date: Dec 2026 --> Sep 2025

P3, N=500, Recruiting, National Cancer Institute, Naples

Interpretation The use of OncoPanel resulted in more precise targeting of cetuximab and panitumumab, but there was no change in incremental cost or quality-adjusted survival. Understanding the balance of costs achieved in practice can provide insight into the effect of future changes in testing policy, test cost, treatment eligibility, or drug prices in this setting.

P2, N=75, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Jul 2024 | Trial primary completion date: Mar 2025 --> Jul 2024

Apart from Cetuximab, other anti-EGFR mAbs have been developed, such as Panitumumab. Organoids can reflect tumor genetic heterogeneity found in the tissue of origin, representing a unique tool for personalized medicine. Thus, CRC-derived organoid cultures are a smart model for studying the tumor microenvironment and for the preclinical assay of anti-EGFR drugs.

In this secondary analysis of a phase II randomized clinical trial, patient-reported DRQOL outcomes correlated with skin toxicity according to NCI-CTCAE during induction therapy. Maintenance therapy with FU/FA + Pmab was associated with deteriorated DRQOL versus FU/FA alone in patients with RAS wt mCRC.

P2, N=118, Active, not recruiting, Federation Francophone de Cancerologie Digestive | Trial primary completion date: Apr 2024 --> Dec 2024

P3 | N=700 | Not yet recruiting | Sponsor: IFOM ETS - The AIRC Institute of Molecular Oncology

Therefore, we reformatted six therapeutic EGFR antibodies (cetuximab, panitumumab, nimotuzumab, necitumumab, zalutumumab, and matuzumab) into the IgA3.0 format, which is an IgA2 isotype that has been adapted for clinical application. IgA3.0 matuzumab exhibited reduced receptor internalization compared to the other antibodies, possibly accounting for its superior in vivo Fc-mediated tumor cell killing efficacy. In conclusion, reformatting EGFR antibodies into an IgA3.0 format increased Fc-mediated killing while retaining Fab-mediated functions and could therefore be a good alternative for the currently available antibody therapies.

In monolayer culture, caspase-9 effectively suppressed the migration and invasion of MDA-MB-231 cells, comparable to the anti-metastatic agent panitumumab (Pan)...Moreover, pre-treatment with activated caspase-9 sensitized cells to the chemotherapy of doxorubicin, thereby enhancing its effectiveness. In conclusion, the anti-metastatic potential of caspase-9 presents avenues for the development of novel therapeutic approaches for TNBC/metastatic breast cancer. Although more studies need to figure out the exact involving mechanisms behind this behavior.

P2, N=35, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed

P=N/A, N=46, Completed, Xilis, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Mar 2024 | Trial primary completion date: Dec 2025 --> Nov 2023

P1, N=0, Withdrawn, Stanford University | N=14 --> 0 | Suspended --> Withdrawn

These findings suggested that these regimens were not sufficiently cost-effective, although they have excellent therapeutic efficacy. From the economic point of view, these combination regimens were inferior to FOLFIRI alone.

Nimotuzumab (one trial), zalutumumab (one trial) and panitumumab (one trial) were the monoclonal antibodies evaluated in the remaining three trials. Finally, three phase III trials tested the effectiveness of cetuximab plus RT in the treatment of human papillomavirus-positive oropharyngeal carcinoma, and found it to be inferior compared with cisplatin-RT in terms of OS, PFS and failure-free survival. Based on the aforementioned findings, it is difficult to conclude that anti-EGFR therapy in any form has an advantage over conventional chemoradiation in the treatment of LAHNSCC.

P1, N=5, Active, not recruiting, Rutgers, The State University of New Jersey | Completed --> Active, not recruiting | Trial completion date: Feb 2023 --> Feb 2025 | Trial primary completion date: Feb 2023 --> Feb 2025

Targeted therapies for NMSCs may be possible with the use of RTKIs. The majority of studies focused on utilizing epidermal growth factor receptor inhibitors as the primary class of RTKIs for the treatment of NMSC. Other RTKIs were only employed in experimental investigations. Research indicates that RTKIs could potentially serve as a suitable alternative for elderly patients who are unable to undergo chemotherapy and radiotherapy.

P1, N=1200, Recruiting, Amgen | Phase classification: P1/2 --> P1

In RAS/BRAF wt mCRC patients, an anti-EGFR rechallenge provides a feasible therapeutic option with clinical benefit (survival) and a manageable safety profile.

P2; N=84 --> 12

P2, N=56, Active, not recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Mar 2024 --> Dec 2024

TRIPLETE is a phase III trial where 435 pts with RAS/BRAF wt mCRC were randomized to receive first-line FOLFOX/panitumumab (pan) or mFOLFOXIRI/pan. Pts enrolled in the TRIPLETE trial with available tissue and plasma at baseline (BP), and plasma at the time of disease progression (PDP) were included... In contrast to previous data, negative hyperselection both through tissue and plasma analysis failed to demonstrate a prognostic role among pMMR RAS/BRAF wt mCRC pts treated with first-line chemotherapy plus pan. The confounding effect of the associated chemotherapy is a potential explanation for this finding.