EGFR mutation

P1, N=42, Recruiting, Alpha Biopharma (Jiangsu) Co., Ltd. | Not yet recruiting --> Recruiting

We present the case of a 60-year-old non-smoking woman previously treated for luminal B human epidermal growth factor receptor 2 (HER2)-positive invasive breast carcinoma with surgery, AC60 chemotherapy, trastuzumab, breast radiotherapy, and hormone therapy at the Mohammed VI Oncology Center in Casablanca, Morocco. The patient received neoadjuvant vinorelbine-cisplatin chemotherapy followed by volumetric modulated arc therapy (VMAT) thoracic radiotherapy at 66 Gy, achieving clinical and radiological stabilization. This case highlights the occurrence of a second driver-negative primary lung adenocarcinoma in a non-smoker and underscores the importance of integrated histopathological, immunohisto chemical, and targeted molecular evaluation in distinguishing primary tumors from metastases, as well as the potential role of post-therapeutic carcinogenesis.

P2, N=30, Active, not recruiting, National Cancer Centre, Singapore | Trial primary completion date: Mar 2026 --> Oct 2025

We report the case of a 61-year-old woman diagnosed with stage IV lung adenocarcinoma with brain metastasis harboring an EGFR exon 19 deletion (p.E746_A750del), who acquired resistance to osimertinib through a ROS1 fusion bypass pathway. The patient achieved a survival of over 6.5 years from initial diagnosis through ongoing adjustments to targeted therapy, including sequential treatment with crizotinib, entrectinib, and lorlatinib...Notably, we observed an interesting phenomenon with both crizotinib and entrectinib: while initial treatment led to intolerable adverse reactions requiring discontinuation, subsequent reintroduction of the same agent was well-tolerated. This case report aims to provide potential treatment strategies for patients with similar complex co-mutations.

These challenges include the need for preimplantation genetic testing for monogenic disorders (PGT-M) to reduce the risk of transmitting cancer-predisposition gene mutations to their offspring and the consideration of a gestational carrier, as current guidelines prohibit pregnancy during targeted molecular therapy. Maintaining a normal ovarian reserve would allow the opportunity to delay in vitro fertilization (IVF) until a more optimal time, thereby improving reproductive planning for patients who already manage the burdens of hereditary cancer syndrome.

This study estimated the cost-effectiveness of sacituzumab tirumotecan (Sac-TMT) versus pemetrexed-platinum chemotherapy as second-line therapy for advanced EGFR-mutated non-small cell lung cancer (NSCLC) in China. A price reduction exceeding 73.81% would bring the ICER below the WTP threshold. At current prices, Sac-TMT is not cost-effective as second-line therapy for advanced EGFR-mutated NSCLC in China.

The prepared NCM-ERL-Liposomes showed enhanced internalization, triggered caspase-3/7-mediated apoptosis (1.42-fold increase), and suppressed p-EGFR/p-STAT3, indicating adequate payload protection and targeted intracellular release. These results establish a translational platform that requires PK/PD studies in resistant NSCLC models to support precision oncology therapeutics.

Free energy of binding calculations using the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method supported these findings, with D4 showing the most favourable interaction, dominated by Van Der Waals and electrostatic contributions from key catalytic amino acid. Our research, with further experimental validation, could be helpful to support that certain MET inhibitors, especially D4, are promising competitive inhibitors of EGFRwt, offering potential for the development of new therapeutic strategies targeting EGFRwt-driven cancers.

As of December 2025, osimertinib-based regimens, whether used as monotherapy or in combination with chemotherapy, have emerged as potential options in this field and are supported by high-level evidence-based medicine. The article also discusses the limitations of immunotherapy in the EGFR-mutant NSCLC population and the future development trends of combination strategies, emphasizing that biomarker-guided individualized therapy represents the corner direction moving forward.

P1/2, N=32, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2028

P2, N=154, Not yet recruiting, Anhui Provincial Cancer Hospital

P2, N=50, Recruiting, Taipei Medical University Hospital | Not yet recruiting --> Recruiting