A Phase 1b/2a Study Evaluating the Pharmacokinetics, Safety, and Efficacy of Nanogenistein in Combination with Chemoradiotherapy for Non-small Cell Lung Cancer

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Conference Proceeding

Publication Date


Publication Title

International Journal of Radiation Oncology Biology Physics


Purpose/Objective(s): Radiation therapy (RT) remains a critical component of locally advanced (LA) and limited metastatic non-small cell lung cancer (NSCLC) but is associated with significant risks of pneumonitis, esophagitis, and major cardiac events. Nanogenistein (NG) is a radioprotectant that promotes DNA repair, cell cycle arrest and anti-inflammatory signaling to mitigate RT-associated toxicities. The objective of this phase 1b/2a trial is to evaluate the safety, pharmacokinetics (PK), and efficacy of NG in combination with concurrent chemoradiotherapy for NSCLC.

Materials/Methods: Patients with newly diagnosed stage II, III or IV (oligometastatic) NSCLC planned for 60-70/1.8-2.0 Gy RT and concurrent weekly paclitaxel/carboplatin were eligible. Patients were treated daily with a self-administered, oral suspension of NG at one of three dose levels (500, 1000, or 1500 mg) starting prior to and continuing during the entire course of chemoradiotherapy (up to 8 weeks). Three cohorts (n = 7/cohort) were enrolled sequentially. PK analysis was completed for NG, paclitaxel and carboplatin. Tumor response was defined per RECIST 1.1 criteria. CT scans were obtained during chemoradiotherapy, consolidation, and every 2-3 months following RT completion. Adverse events (AEs) were reported using the NCI CTCAEv4 and used to monitor dose-limiting toxicities (DLTs). Quality of life measurements included UCSD-SOBQ, FACT-L TOI and a swallowing diary.

Results: Enrolled patients (n = 21) were a median of 69 years (range 50-84), predominantly Caucasian (n = 19) and female (n = 11), and had stage II (n = 5), III (n = 14) or IV (n = 2) disease. NG was well tolerated and no DLTs were identified. NG PK did not interfere with chemotherapeutic PK. AEs were not dose dependent and those possibly (n = 10), probably (n = 1) or definitely (n = 0) attributable to NG treatment were mild GI events (n = 8, all grade 1), fatigue (n = 1, grade 2), anorexia (n = 1, grade 2), and dysgeusia (n = 1, grade 1). Overall, 1 major cardiac event, 1 grade 3 esophagitis, and 2 cases of grade ≥2 pneumonitis occurred. Patient weight loss was ≤ 5%, pulmonary function (0, 9- and 13-months post-RT), and FACT-L TOI (0, 3, 6- and 13-months post-RT) remained stable across all cohorts (all p>0.05). Tumor response rate was 70%, with a complete response rate of 15%. The median progression-free survival across cohorts was 15.6 months, and the median overall survival was not reached at a median of 15.9 months follow-up.

Conclusion: In this study, NG was found to be safe and well tolerated, with an incidence of Grade ≥2 hematological and normal tissue toxicities both less than that observed in RTOG 0617. These encouraging safety and efficacy data support advancing the drug to an adequately powered, randomized, double-blind, placebo-controlled phase 2b study that is planned in LA-NSCLC patients.





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