P2, N=38, Active, not recruiting, Australasian Gastro-Intestinal Trials Group | Recruiting --> Active, not recruiting | N=90 --> 38 | Trial primary completion date: Apr 2026 --> Jan 2026

P=N/A, N=6, Active, not recruiting, Australasian Gastro-Intestinal Trials Group | Recruiting --> Active, not recruiting | Phase classification: P2 --> PN/A | N=75 --> 6 | Trial completion date: Jun 2025 --> Dec 2027 | Trial primary completion date: Jun 2024 --> Dec 2025

P1, N=30, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

PDC treatment significantly suppresses tumor growth in in vivo KRAS mutant xenograft model, demonstrating superior efficacy compared with cetuximab-based regimens and controls, without observable body weight loss. This strategy uses EGFR as a delivery portal instead of a signaling target, enabling KRAS independent anti-tumor activity. These findings indicate a non-canonical EGFR mediated delivery approach with potential translational relevance for the treatment of therapy resistant CRC.

Ficerafusp alfa plus pembrolizumab demonstrated favorable safety and tolerability with promising antitumor activity in the first-line treatment of R/M HNSCC, particularly in those with HPV-negative tumors.

P1/2, N=40, Recruiting, Sichuan University | Trial completion date: Feb 2026 --> Dec 2028 | Trial primary completion date: Dec 2025 --> Dec 2027

Although the primary endpoint was not met, the combination provided durable control of MPE and was well tolerated, suggesting potential value in symptom-focused management of this high-risk subgroup.

P1, N=86, Active, not recruiting, Taizhou Mabtech Pharmaceutical Co.,Ltd | Recruiting --> Active, not recruiting | Trial completion date: Feb 2026 --> May 2026

OB-001, a KinetiSol® amorphous solid dispersion formulation of elacridar, was developed to overcome poor bioavailability of crystalline elacridar and evaluated as a strategy to enhance osimertinib brain delivery. OB-001 selectively boosts osimertinib brain exposure while sparing systemic PK. These preclinical data support further evaluation of OB-001 as a strategy to enhance CNS efficacy of osimertinib in EGFR-mutant NSCLC.

Treatments include surgery, radiation, and chemotherapy, with ongoing trials investigating agents like cetuximab, cisplatin, and Tazemetostat. Tazemetostat, targeting KMT2D-related DNA (deoxyribonucleic acid) methylation, and cetuximab, targeting the PIK3CA signaling cascade, may offer therapeutic benefits. Further research on mutation-specific therapies could improve treatment strategies.

Outcomes following progression on chemotherapy and MAPK-targeted therapy with Encorafenib plus Cetuximab remain poor, highlighting an unmet need for effective later-line treatments. We discuss the mechanistic framework by which a subset of BRAFV600E-mutant MSS mCRC may respond to immune checkpoint inhibition through an inflamed immune microenvironment driven by constitutive MAPK signalling. This case illustrates the interplay between tumour-agnostic biomarkers such as TMB-high and tumour-specific context, and highlights the value of longitudinal genomic profiling, including ctDNA, to identify resistance mechanisms and guide treatment selection.

First-line osimertinib provides prolonged OS and meaningful economic benefits over second-generation TKIs. Given the higher toxicity burden of sequential therapy despite similar survival outcomes, our findings support the implementation of first-line osimertinib to optimize patient experience and reduce health care utilization in metastatic EGFR-mutant NSCLC.