Study Using a Drug-device Combination Product to Determine Safety, Tolerability and Antitumor Activity for Patients With Advanced, Non-small Cell Lung Cancer

This is an open label, multi-center Phase 1/2 study of NHT102, 5-Azacytidine Mircronised, Dry Powder Formulation Delivered by a Novel Inhalation Delivery System (device constituent product \[DCP\]). The study will enroll patients with advanced NSCLC limited to the lung and thoracic region. The study consists of three sequential parts: Part 1 (Dose Escalation): Approximately five dose levels of NHT102 will be evaluated using a standard 3+3 design to determine dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD). Patients receive NHT102 once daily on Days 1-5 and Days 15-19 of each 28 day cycle. A Safety Review Committee (SRC) will review safety data after each cohort completes the DLT evaluation period. Part 2 (Dose Optimization): At least two dose levels selected from Part 1 will be evaluated using Simon's two stage design. Each dose level will enroll up to 25 evaluable patients to assess anti-tumor activity, safety, pharmacokinetics (PK), pharmacodynamics, and exploratory biomarkers. Part 3 (Dose Expansion): The recommended Phase 2 dose (RP2D) selected from Part 2 will be further evaluated to characterize safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity. Patients will continue treatment until disease progression, unacceptable toxicity, withdrawal of consent, investigator decision, or study termination. Follow up includes safety assessment at 30 days after end of treatment and 6 month survival follow up.