An Open-Label Pilot Study Evaluating the Safety, Feasibility, and Preliminary Clinical Activity of Inhaled Cromolyn Sodium in Participants With Locally Advanced Lung Cancer

Scientific Background and Rationale

Lung cancer remains a leading cause of cancer-related mortality worldwide despite substantial advances in molecularly targeted therapies, immunotherapy, radiation therapy, and multimodality treatment approaches. Increasing evidence indicates that, in addition to intrinsic tumor biology, the tumor microenvironment plays a critical role in disease progression, immune evasion, therapeutic resistance, and metastatic dissemination. Consequently, there is growing interest in therapeutic strategies designed to modulate tumor-associated inflammatory and stromal processes that contribute to cancer progression.

Mast cells are resident immune cells that participate in both innate and adaptive immune responses and are increasingly recognized as important components of the tumor microenvironment. In lung cancer, mast cell infiltration has been observed within both primary tumor tissue and surrounding stromal compartments. Experimental and translational studies have suggested that mast cells may contribute to tumor-associated inflammation through the release of cytokines, chemokines, growth factors, angiogenic mediators, and proteolytic enzymes capable of influencing immune regulation, angiogenesis, extracellular matrix remodeling, and cellular proliferation.

Cromolyn sodium is an FDA-approved mast cell stabilizing agent with a long-established clinical safety profile following inhalational administration for allergic respiratory disorders. The drug inhibits mast cell degranulation and reduces the release of multiple inflammatory mediators involved in downstream immune and inflammatory signaling pathways. In addition to its effects on mast cells, preclinical investigations have suggested broader effects on inflammatory processes involving macrophages, eosinophils, neutrophils, and other immune-regulatory cell populations implicated in tumor-associated inflammation.

Preclinical studies evaluating mast cell inhibition and modulation of inflammatory signaling pathways have generated interest in the potential role of tumor microenvironment-directed therapeutic strategies in solid tumors. Although the clinical significance of these observations remains uncertain, available experimental data provide a biologically plausible rationale for exploratory clinical investigation of cromolyn sodium in lung cancer.