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Vidutolimod in Combination With Atezolizumab With and Without Radiation Therapy in Patients With PD-1/PD-L1 Blockade−Resistant Advanced Non−Small Cell Lung Cancer

Open AccessPublished:October 25, 2022DOI:https://doi.org/10.1016/j.jtocrr.2022.100423
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      Abstract

      Introduction

      Vidutolimod, a CpG-A Toll-like receptor 9 agonist, was investigated in a phase 1b study (CMP-001-003; ClinicalTrials.gov, NCT03438318) in combination with atezolizumab ± radiation therapy (RT) in patients with advanced non–small cell lung cancer (NSCLC).

      Methods

      Patients with progressive disease following anti–programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy received either vidutolimod and atezolizumab (part A) or vidutolimod, atezolizumab, and RT (part B). Primary objective was to evaluate the safety of vidutolimod and atezolizumab ± RT. Key secondary endpoint was best objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1.

      Results

      Between March 28, 2018, and July 25, 2019, 29 patients were enrolled and received ≥1 dose of vidutolimod (part A, n = 13; part B, n = 16). Intratumoral injections of vidutolimod were administered successfully, including injection of visceral lesions. The most common treatment-related adverse events (≥30%) were flu-like symptoms and hypotension. No objective responses were observed; 23.1% and 50.0% of patients in parts A and B, respectively, had stable disease as best response. In parts A and B, 15.4% and 25.0% of patients, respectively, had tumor shrinkage (<30% decrease in tumor size, nonirradiated). Enrollment was stopped due to lack of objective responses. In the two patients with initial tumor shrinkage in part A, a strong serum induction of C-X-C motif chemokine ligand 10 was observed.

      Conclusions

      Vidutolimod and atezolizumab ± RT had a manageable safety profile, with minimal clinical activity in heavily pretreated patients with PD-1/PD-L1 blockade–resistant NSCLC.

      Keywords