Vectibix (panitumumab)

P1, N=600, Recruiting, Erasca, Inc. | N=200 --> 600

Triplet chemotherapy based on FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) has achieved high response rates and deep tumor shrinkage. In combination with molecularly targeted agents, triplet therapy plus bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, has demonstrated superior efficacy compared with doublet chemotherapy plus bevacizumab. In patients with RAS/BRAF wild-type tumors, combination therapy with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies such as cetuximab and panitumumab has also shown improved survival outcomes, although toxicity remains a major concern...This review outlines the historical development of triplet therapy in mCRC, summarizes the major clinical trials investigating triplet chemotherapy combined with molecularly targeted agents, and discusses direct comparisons between anti-VEGF- and anti-EGFR-based strategies. Particular emphasis is placed on practical considerations for clinical implementation, including toxicity management, dose optimization, and multidisciplinary supportive care.

P2, N=150, Not yet recruiting, Verastem, Inc.

We report a case of metastatic CRC that achieved CR following second-line treatment with FOLFIRI plus ramucirumab after disease progression on first-line FOLFOX plus panitumumab therapy...In the present case, a watch-and-wait strategy was selected to prioritize organ preservation. Given the lack of consensus, further investigation is required to define the optimal strategy for patients achieving CR.

For OS, both cetuximab + chemotherapy [hazard ratio (HR)=0.853; 95% CI: 0.775-0.938; P=0.001] and panitumumab + chemotherapy (HR=0.855; 95% CI: 0.738-0.992; P=0.038) exhibited statistically significant superiority compared with bevacizumab + chemotherapy...In the present sensitivity analysis, UDP glucuronosyltransferase family 1 member A1-guided bevacizumab + 5-fluorouracil, leucovorin and irinotecan demonstrated favorable outcomes, with OS and PFS P-scores of 0.932 and 0.992, respectively; however, these findings were derived from a single trial with limited comparability...Treatment benefit from anti-EGFR therapy was markedly influenced by primary tumor location, with notable benefit observed in left-sided tumors and no benefit in right-sided tumors. These findings support tumor sidedness-guided treatment selection in clinical practice, favoring anti-EGFR-based therapy for left-sided and bevacizumab-based therapy for right-sided RAS wild-type mCRC.

Panitumumab was complexed to 197gHg/197mHg after conjugation to a bifunctional chelator or labeled directly with 197gHg/197mHg. These radioimmunoconjugates bound specifically to EGFR on human breast cancer cells and caused DNA double-strand breaks that decreased their clonogenic survival. The radioimmunoconjugates localized in EGFR-overexpressing MDA-MB-468 tumours in mice but there was high kidney uptake, suggesting in vivo release of some 197gHg/197mHg. Competition between complexation of 197gHg/197mHg to a bifunctional chelator and binding to endogenous mercury binding sites in panitumumab presents challenges for radiolabeling and may explain the apparent release of some 197gHg/197mHg in vivo. Alternative labeling strategies such as a 2-step method involving conjugation of the preformed 197gHg/197mHg bifunctional chelator to panitumumab could be explored to address these challenges.

P2, N=7, Terminated, Northwestern University | Trial completion date: Jul 2030 --> Apr 2026 | Active, not recruiting --> Terminated | Trial primary completion date: May 2026 --> Oct 2025; The study was closed due to accrual.

P3, N=450, Recruiting, Amgen | Trial completion date: Aug 2031 --> Apr 2032 | Trial primary completion date: Jan 2028 --> Sep 2028

P1/2, N=90, Recruiting, Isofol Medical AB | Trial completion date: Mar 2029 --> Dec 2029 | Trial primary completion date: Mar 2028 --> Nov 2028 | N=60 --> 90

P2, N=7, Active, not recruiting, Northwestern University | Recruiting --> Active, not recruiting | N=43 --> 7 | Trial primary completion date: Jul 2028 --> May 2026

We applied SSP to tumor tissues from participants with head and neck squamous cell carcinoma and pancreatic ductal adenocarcinoma who received the antibody panitumumab-IRDye800 in phase 1 trials. SSP identified pronounced spatial heterogeneity in single-cell drug delivery and target engagement, shaped by conserved stromal barriers, including periostin-rich extracellular matrix assemblies and fibroblast-activation-protein-positive cancer-associated fibroblast neighborhoods, which were associated with reduced antibody delivery in both tumor types. SSP measures drug-target-TME interactions in human tumors and can support studies of resistance mechanisms, dosing strategies and discovery of spatial biomarkers for precision oncology.

P=N/A, N=500, Active, not recruiting, Barretos Cancer Hospital