EGFR mutation

P2, N=50, Not yet recruiting, Fred Hutchinson Cancer Center

P1/2, N=70, Terminated, VBI Vaccines Inc. | Recruiting --> Terminated; VBI Bankruptcy

Lung adenocarcinomas with PIK3CA mutations exhibit distinct clinicopathological characteristics in terms of gender, age, smoking history, differentiation degree, and clinical stage. Acquired drug resistance in lung adenocarcinoma may be accompanied by PIK3CA mutations, but PIK3CA mutation is not the main mechanism of targeted therapy resistance in lung adenocarcinoma patients.

The model described in this work is suitable for allowing translation to iPSC-derived macrophages to generate clinically applicable future cell therapy approaches in solid tumors expressing mutated variant EGFRVIII.

nCIT establishes a new standard of care for resectable non-small cell lung cancer, offering improved pathological and survival outcomes while preserving surgical safety. Future research should focus on unresolved issues such as patient selection, biomarker integration and the role of adjuvant immunotherapy to refine personalized treatment strategies.

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

However, current standard of care treatments such as surgical resection, radiotherapy, temozolomide, and tumor treating fields have reached a therapeutic plateau, highlighting the urgent need for new therapeutic strategies...We further synthesize recent advances in spatial and longitudinal profiling technologies to describe the dynamic tumor immune ecosystem. We discuss how spatial compartmentalization and evolutionary processes collectively drive immune escape and therapeutic resistance, and highlight emerging strategies including adaptive immunotherapy, precision targeted delivery, and multimodal monitoring to overcome these challenges.

It also outlines next generation directions, including higher order multispecific constructs, conditionally active antibodies, and payload conjugated multispecific formats. To consolidate these agents as an established therapeutic modality in oncology, priority should be given to rigorous understanding of mechanisms of action and toxicity, alongside rational optimisation of construct design and dosing, supported by robust prospective translational programmes.

The study further examines how oncogenic mutations in genes like EGFR, KRAS, TP53, KEAP1, and IDH1 reshape ferroptosis susceptibility or resistance through alterations in metabolic pathways, redox homeostasis, and tumor microenvironment interactions. By highlighting mutation-specific sensitivities, this work underscores the potential of ferroptosis-targeted strategies to surmount therapeutic resistance, synergize with conventional treatments like chemotherapy and immunotherapy, and drive precision oncology forward, paving the way for enhanced clinical outcomes across a broad spectrum of cancers.

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=288, Active, not recruiting, AbbVie | Trial completion date: Jun 2026 --> Nov 2027 | Trial primary completion date: Jun 2026 --> Nov 2027

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.