Vectibix (panitumumab)

Anti-EGFR monoclonal antibodies, cetuximab and panitumumab, have demonstrated survival benefit in selected patients, particularly those with left-sided, RAS wild-type tumors. We also discuss mechanisms of resistance such as pathway reactivation, receptor mutations, and epithelial-to-mesenchymal transition, alongside emerging approaches, including combination regimens, ctDNA-guided rechallenge, and genotype-specific inhibitors. Collectively, these insights highlight the evolving landscape of precision oncology in CRC and the importance of molecular stratification to optimize EGFR-targeted therapy and overcome resistance.

P1, N=364, Recruiting, Astellas Pharma Inc

P2, N=88, Not yet recruiting, Korea University Anam Hospital

With this agent, we prepared a dye-panitumumab (Pan) conjugate, (POR-1)3-Pan, for in vivo imaging of epidermal growth factor receptor (EGFR)-positive tumors...Moreover, it enables small tumor nodules (<3 mm) to be visualized clearly. Overall, this study establishes a high-performance NIR dye platform for the development of dye-antibody conjugates for applications in fluorescence image-guided surgery.

Trastuzumab-based combinations and HER2-selective tyrosine kinase inhibitors such as tucatinib have demonstrated durable responses and favorable safety profiles in heavily pretreated patients. This review summarizes current evidence from pivotal phase II and III clinical trials, translational studies, and real-world data evaluating EGFR-, BRAF-, and HER2-directed therapies in colorectal cancer. Particular emphasis is placed on biomarker-guided patient selection, mechanisms of resistance, and emerging combination strategies that continue to refine precision oncology approaches in mCRC.

P2, N=14, Recruiting, Amgen

This retrospective multi-center study included 600 RAS wild-type advanced CRC patients (development cohort: 420 patients from two centers; external validation cohort: 180 patients from an independent center) treated with EGFR inhibitors (cetuximab/panitumumab) plus anti-angiogenic agents (bevacizumab/fruquintinib/regorafenib) between 2018 and 2021. As a supplementary tool to current clinical guidelines, the model can partially address the problem of clinical response heterogeneity in combination therapy and provide simple decision support for clinicians in primary and secondary hospitals with limited detection conditions. However, the model has certain limitations in long-term prognostic prediction and needs to be further optimized and validated in larger, multi-center prospective cohorts before it can be translated into clinical practice of precision oncology.

Tumour-targeted fluorescence-guided surgery (Ttfgs) enhances intraoperative precision in gastrointestinal cancer treatment. Translation of (Ttfgs) into clinical practice is limited by heterogeneity, regulatory hurdles, biomarker variability and absence of phase III trials. Innovations such as multimodal tracers and theranostic agents may further enhance the precision and therapeutic potential of Ttfgs.

P2, N=197, Recruiting, Gruppo Oncologico del Nord-Ovest | N=140 --> 197

P1, N=2, Active, not recruiting, Roswell Park Cancer Institute | Trial primary completion date: Jul 2025 --> Feb 2026

P2, N=14, Recruiting, Amgen

Adagrasib monotherapy yielded a median PFS of 4.4-5.6 months, an OS of 10-19.8 months, and an ORR of 19-23%, while its combination with cetuximab reported a PFS of 6.9 months, an OS of 13.4-15.9 months and an ORR of 34-46%...When combined with panitumumab, 960 mg sotorasib demonstrated better results with a PFS of 5.6-5.7 months, OS of 15.2 months and an ORR of 12.5-30%. Similarly, divarasib monotherapy led to a PFS of 5.6-6.9 months and an ORR of 20%, while its combination with cetuximab resulted in a PFS of 8.1 months and an ORR of 62.5%. Combination therapy of olomorasib and MK-1084, which are new-generation KRAS p.G12C (c.34G > T) inhibitors, with cetuximab also demonstrated highly promising efficacy with ORR of 38-44% and 50%, respectively...Initial results of KRAS-G12C inhibitors appear highly promising when they are combined with anti-EGFR therapy compared to historical therapeutic agents indicated for patients with chemotherapy-refractory CRC. Encouraging benefits warrant frontline trials with these novel therapeutics.