Vectibix (panitumumab)

P1, N=13, Terminated, MapKure, LLC | N=64 --> 13 | Trial completion date: May 2027 --> Mar 2025 | Recruiting --> Terminated | Trial primary completion date: May 2027 --> Mar 2025; Funding terminated due to business reasons

P3, N=160, Active, not recruiting, Amgen | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Mar 2025 --> Jul 2025

In the phase III CodeBreaK 300 study, sotorasib 960 mg-panitumumab significantly prolonged progression-free survival (PFS) versus investigator's choice (trifluridine/tipiracil or regorafenib) in patients with KRAS G12C-mutated chemorefractory metastatic colorectal cancer (mCRC). No new safety signals were observed. Although not statistically significant, the observed OS HR and ORR along with prior PFS and safety findings support sotorasib 960 mg-panitumumab as a standard of care in patients with chemorefractory KRAS G12C mCRC.

P2, N=26, Active, not recruiting, Emory University | N=40 --> 26 | Trial completion date: Oct 2024 --> Oct 2025

P2, N=44, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Aug 2025 --> Apr 2025 | Trial primary completion date: Aug 2025 --> Apr 2025

Medications like Nimotuzumab, Cetuximab, and Panitumumab target the Epidermal Growth Factor Receptor (EGFR), which EGF activates. HER2, activated by ligands, is the focus of drugs like Trastuzumab and Pertuzumab. The PD-1/PD-L1 and CTLA-4 pathways, as the immune checkpoints, which involve T cells, are targeted by medications like Ipilimumab...HIF1A-AS1, CRNDE-h, NEAT1, ZFAS1, and GAS5, along with IGFBP-2, have demonstrated significant CRC diagnostic capacity. Compared to CRC patients with low HIF1A-AS1 expression, individuals with high expression levels were linked to a worse 5-year survival rate.

When sotorasib was used alone, the objective response rate (ORR) ranged from 7.1 to 9.7%, with disease control (DC) rates of 73.8 to 82.3% and a median progression-free survival (PFS) spanning 4-5.6 months...Meanwhile, pairing adagrasib with cetuximab led to a 42% ORR and a median PFS of 6.9 months, surpassing the 19% ORR observed with adagrasib alone. Divarasib monotherapy produced a 36% ORR and an 85.5% DC rate, with a PFS of 5.6 months; in tandem with cetuximab, those numbers climbed to a 62.5% ORR and a PFS of 8.1 months...Overall, KRAS G12C inhibitors appear to offer meaningful benefits for CRC patients, particularly when used alongside EGFR inhibitors like cetuximab or panitumumab. However, further large-scale, randomized trials are needed to refine dosing strategies and gain a clearer picture of both efficacy and potential risks.

In HNSCC patients infused with a molecularly targeted fluorescent tracer, endogenous expression of the target antigen can be used as a reference standard to detect LN metastasis. Additionally, the performance of the background in determining metastatic LN can be improved by utilizing patient-specific reference standards.

Currently, additional mutations of the pathway, including non-exon 2 mutations in KRAS, mutations in the homologous GTPase NRAS, in kinase BRAF and PIK3CA and other pathway proteins, have been added in the evaluation for responsiveness prediction to cetuximab and panitumumab. In this review, the predictive biomarker landscape for anti-EGFR monoclonal antibody inhibitors in metastatic colorectal cancers with no extended RAS and BRAF mutations will be examined.

It is also associated with resistance against epidermal growth factor receptor (EGFR)-targeted therapies like cetuximab and panitumumab, for treatment of RAS wild-type mCRC. Furthermore, anti-HER2 therapies exhibited non-toxic profile and high efficacy in chemorefractory cases. This review delves into modern management of anti-HER2 therapies in CRC with a particular focus on recent advances and current knowledge about the prognostic and predictive value of HER2.

The review discusses the evolution of CRC treatment from traditional chemotherapy to the advent of targeted therapies like Bevacizumab and Cetuximab. With a notable increase in PFS and objective response rates and a well-tolerated safety profile, this combination therapy emerges as a potential new standard of care. The results present an optimistic outlook for patients resistant to conventional therapies.

P2, N=56, Completed, UNC Lineberger Comprehensive Cancer Center | Active, not recruiting --> Completed

P2, N=390, Recruiting, AbbVie | Not yet recruiting --> Recruiting

P1, N=1200, Recruiting, Amgen | Trial completion date: Mar 2028 --> Dec 2027

We divided the results by subsite for markers: lymph node analysis (microRNAs, myosin-5a (MYO5A), ring finger protein 145 (RNF145), F-box only protein 32 (FBXO32), CTONG2002744, cytokeratin 14 (CK14), eukaryotic initiation factor 4E (eIF4E), desmoglein-3 (DSG3), microsatellite D9S171, squamous cell carcinoma antigen, cytokeratin, tumor budding score, human papillomavirus-DNA (HPV-DNA), tumor infiltrating lymphocytes, sentinel lymph node analysis techniques, single fiber reflectance spectroscopy, radiological techniques), tumor tissue analysis (activin A, carcinoma-associated fibroblasts, cyclins, β-catenin, histopathology, genetic amplifications, DNA methylation, ecotropic viral integration site 1, CC-chemokine receptor 7, melanoma associated-A antigens, vascular endothelial growth factor-C (VEGF-C), panitumumab, epidermal growth factor receptor (EGFR), cornulin, total protein analysis, CD133, NANOG homeobox, neurogenic locus notch homolog protein 1 (NOTCH1), metastasis-associated protein 1, 14-3-3-zeta, E-cadherin, focal adhesion kinase, p-epithelial-mesenchymal transition (EMT), small proline rich protein 1B (SPRR1B), transcription factor NKX3-1, DNA copy number aberrations, microfibril-associated protein 5 (MFAP5), troponin C1, slow skeletal and cardiac type (TNNC1), matrix Gla protein (MGP), fibroblast growth factor binding protein 1 (FBFBP1), F-box protein 32 (FBXO32), fatty acid binding protein 5, B cell-specific Moloney murine leukemia virus integration site 1, podoplanin, p53, Bcl-2, epidermal growth factor receptor (EGFR), Ki67, cyclin D1, cox-2, semaphorin-3F, neuropilin-2, histologic features, cellular dissociation grade, prospero homeobox protein 1, radiologic features, Ki-67, poly (ADP-ribose) polymerase (PARP), Bcl-2 associated agonist of cell death (BAD), caspase-9, vascular endothelial growth factor A (VEGF-A), HPV, p16, methylation status of long interspersed element 1 (LINE-1) and Alu elements, mesenchymal-epithelial transition (MET), gene expression analyses, molecular subtypes) and blood markers (standard blood analysis indexes and ratios, circulating tumor cells, HPV-DNA, CD-31, bone marrow analysis). Several promising markers were identified, including miR-205, desmoglein 3 (DSG3), pan-cytokeratin (CK) AE1/AE3, HPV-16, activin-A, cyclin D1, E-cadherin, and neural progenitor lineage (NPL) that demonstrated effectiveness across multiple studies. Future research should focus on exploring combination scoring systems to improve diagnostic precision and optimize treatment selection in HNSCC patients.

Pharmacological KRAS inhibition is a promising new approach to the treatment of many kinds of cancer.

P2, N=80, Terminated, AGITG | Active, not recruiting --> Terminated

P2, N=219, Active, not recruiting, UNICANCER | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=112, Recruiting, Gruppo Oncologico del Nord-Ovest | Trial primary completion date: May 2025 --> May 2026

P2, N=214, Active, not recruiting, Gruppo Oncologico del Nord-Ovest | Recruiting --> Active, not recruiting | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

As RAS/BRAF mutation was negative, the chemotherapy with FOLFOX and panitumumab were administered...The patient has had no major complications or recurrences to date. We report a case in which R0 was achieved after aggressive chemotherapy and laparoscopic two-stage hepatectomy.

P1, N=24, Not yet recruiting, Vanderbilt-Ingram Cancer Center

P2, N=390, Not yet recruiting, AbbVie

P1, N=42, Suspended, Roswell Park Cancer Institute | Recruiting --> Suspended

The combination of CB-839 and panitumumab showed safety and promising preliminary responses, but the study closed early due to CB-839 development termination. The B cell activation signature 'Bscore' emerged as a potential biomarker for EGFR and glutaminase inhibition in mCRC, warranting further studies. These findings suggest opportunities to improve immune response and therapies in glutaminolysis-dependent tumors.

While extending inferences from study populations to specific targets can improve the precision of estimates in small subgroups, violating key assumptions creates bias for many subgroups of interest.

P3, N=450, Recruiting, Amgen | Trial completion date: Apr 2031 --> Aug 2031 | Trial primary completion date: Sep 2027 --> Jan 2028

P3, N=530, Completed, Dutch Colorectal Cancer Group | Recruiting --> Completed | Trial completion date: Jul 2025 --> Jan 2025

P2, N=16, Completed, John Hays | Unknown status --> Completed

This review explores the complexities of targeting colorectal cancer stem cells (CSCs) and the mechanisms contributing to resistance to 5-fluorouracil (5-FU). The efficacy of 5-FU is enhanced by combination therapies such as FOLFOXIRI and targeted treatments like bevacizumab, cetuximab, and panitumumab, particularly in KRAS wild-type tumors, despite associated toxicity...Advances in immunotherapy, including immune checkpoint inhibitors and cancer vaccines, along with nanomedicine-based therapies, offer promising targeted drug delivery systems that enhance specificity, reduce toxicity, and provide novel approaches for overcoming resistance mechanisms. Integrating these innovative strategies with traditional therapies may enhance the effectiveness of CRC therapy by addressing the underlying causes of 5-FU resistance in CSCs.

P3, N=160, Active, not recruiting, Amgen | Trial completion date: Mar 2025 --> Jun 2025

Recently, these and other newly developed inhibitors have been investigated as monotherapies and in combination for metastatic KRASG12C-mutant CRC. This review examines the development of these inhibitors and highlights data supporting the inclusion of sotorasib and adagrasib, in combination with either panitumumab or cetuximab, in the NCCN Guidelines for CRC for the treatment of refractory metastatic disease.

P2, N=59, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

This exploratory analysis from a randomized phase II study shows a non-significant improvement in TTR from the addition of neoadjuvant panitumumab to peri-operative FOLFOX in RAS/BRAF-wt LACC. Hyperselection with EREG/AREG status was associated with increased efficacy. A dedicated prospective trial within a biomarker selected population is under development.

Panitumumab and cetuximab have similar activity when combined with irinotecan as treatment for patients with disease progression with an irinotecan regimen, potentially rescuing the irinotecan activity.

Six-month PFS in both arms was consistent with that achieved with FU/bev, whilst the rate was numerically higher for Arm B. Baseline comprehensive geriatric assessments were feasible and OTU was high. Both treatment arms might be suitable in appropriately selected patients.

This study provides real-world evidence supporting the clinical relevance of rare RAS variants in treatment decision-making for colorectal cancer. Future studies should focus on developing cost-effective comprehensive testing strategies and evaluating alternative treatment approaches for patients with rare RAS variants.

P1/2, N=12, Not yet recruiting, Stanford University | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Aug 2024 --> Aug 2025

For most people, FOLFOX + Bevacizumab may be the best second-line systemic treatment regimen for mCRC. For RAS-mutant populations, FOLFIRI + Bevacizumab + Panitumumab is recommended. However, the therapeutic effect may be affected by the patient's physiological state, and clinicians should apply it based on actual conditions.

P1/2, N=50, Active, not recruiting, Anup Kasi | Recruiting --> Active, not recruiting | Phase classification: P1b/2a --> P1/2 | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Sep 2023 --> Sep 2025

Our data show that baseline serum levels of hepcidin are an independent risk factor for OS in MSS mCRC patients undergoing standard first-line treatment. Further prospective and extensive studies are needed to confirm and validate our findings.

P1, N=14, Recruiting, University of Alabama at Birmingham | Trial primary completion date: Mar 2025 --> Mar 2026