Multicenter Phase 1b/2a Clinical Trial of Radioprotectant BIO 300 Oral Suspension for Patients with Non-Small Cell Lung Cancer Receiving Concurrent Chemoradiotherapy

Purpose: Radiotherapy is part of the standard treatment regimen for non-small cell lung cancer (NSCLC). While radiotherapy is an effective tool to manage NSCLC, it can be associated with significant dose-limiting toxicities. These toxicities can lead to treatment interruption or early termination, worsening clinical outcomes, in addition to reductions in patient quality of life. Based on preclinical efficacy for radioprotection of normal tissues, we evaluated the clinical utility of BIO 300 Oral Suspension (BIO 300; synthetic genistein nanosuspension) in patients with NSCLC.Methods and Materials: In this multicenter, open-label, single-arm, ascending dose phase 1b/2a study, patients were enrolled with newly diagnosed stage II-IV NSCLC planned for 60-70/1.8-2.0Gy radiotherapy and concurrent weekly paclitaxel/carboplatin. Oral BIO 300 (cohort 1, 500 mg/day; cohort 2, 1000 mg/day; cohort 3, 1500 mg/day) was self-administered once-daily starting 2-7 days before initiating concurrent chemoradiotherapy and continued until the end of radiotherapy. The primary endpoint was acute dose-limiting toxicities attributable to BIO 300. Secondary outcomes included pharmacokinetics, pharmacodynamics, overall toxicity profile, quality of life, local response rate and survival.Results: Twenty-one participants were enrolled. No dose-limiting toxicities were reported. BIO 300 dosing did not alter chemotherapy pharmacokinetics. Adverse events were not dose-dependent, and those attributable to BIO 300 (N=11) were all mild to moderate in severity (grade 1, N=9; grade 2, N=2) and predominantly gastrointestinal (N=7). A dose-dependent decrease in serum TGFβ1 levels was observed across cohorts. Based on safety analysis, the maximum tolerated dose of BIO 300 was not met. Patient reported quality of life and weight were largely stable throughout the study period. No patient had progression as their best overall response, and a 65% tumor response rate was achieved (20% complete response rate).Conclusion: The low toxicity rates, along with the pharmacodynamic results and tumor response rates, support further investigation of BIO 300 as an effective radioprotector.