2. Academic Validation
  3. Vidutolimod in Combination With Atezolizumab With and Without Radiation Therapy in Patients With Programmed Cell Death Protein 1 or Programmed Death-Ligand 1 Blockade-Resistant Advanced NSCLC

Vidutolimod in Combination With Atezolizumab With and Without Radiation Therapy in Patients With Programmed Cell Death Protein 1 or Programmed Death-Ligand 1 Blockade-Resistant Advanced NSCLC

  • JTO Clin Res Rep. 2022 Oct 26;4(3):100423. doi: 10.1016/j.jtocrr.2022.100423.
Marcelo V Negrao 1,  Vassiliki A Papadimitrakopoulou 1,  Andrew C Price 2,  Alda L Tam 3,  Muhammad Furqan 4,  Sandeep T Laroia 5,  Erminia Massarelli 6,  Jose Pacheco 7,  John V Heymach 1,  Anne S Tsao 1,  Gary V Walker 2,  Lalit Vora 8,  David Mauro 9,  Heather Kelley 9,  James E Wooldridge 9,  Arthur M Krieg 9,  Jiaxin Niu 10
Affiliations

Affiliations

  • 1 Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • 2 Department of Radiology, Banner MD Anderson Cancer Center, Gilbert, Arizona.
  • 3 Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • 4 Department of Internal Medicine, Carver College of Medicine, University of Iowa Health Care, Iowa City, Iowa.
  • 5 Department of Radiology, Division of Vascular and Interventional Radiology, Carver College of Medicine, University of Iowa Health Care, Iowa City, Iowa.
  • 6 Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California.
  • 7 Department of Medicine-Medical Oncology, University of Colorado, Aurora, Colorado.
  • 8 Department of Diagnostic Radiology, City of Hope, Duarte, California.
  • 9 Checkmate Pharmaceuticals, Cambridge, Massachusetts.
  • 10 Department of Medical Oncology, Banner MD Anderson Cancer Center, Gilbert, Arizona.
PMID: 36925644 DOI: 10.1016/j.jtocrr.2022.100423
Abstract

Introduction: Vidutolimod, a CpG-A TLR9 Agonist, was investigated in a phase 1b study (CMP-001-003; ClinicalTrials.gov, NCT03438318) in combination with atezolizumab with and without radiation therapy (RT) in patients with advanced NSCLC.

Methods: Patients with progressive disease after anti-programmed cell death protein 1 or programmed death-ligand 1 therapy received either vidutolimod and atezolizumab (part A) or vidutolimod, atezolizumab, and RT (part B). The primary objective was to evaluate the safety of vidutolimod and atezolizumab with and without RT. Key secondary end point was best objective response rate per Response Evaluation Criteria in Solid Tumors, version 1.1.

Results: Between March 28, 2018, and July 25, 2019, a total of 29 patients were enrolled and received at least one 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 the patients in parts A and B, respectively, had stable disease as best response. In parts A and B, 15.4% and 25.0% of the patients, respectively, had tumor shrinkage (<30% decrease in tumor size, nonirradiated). Enrollment was stopped owing 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 with and without RT had a manageable safety profile, with minimal clinical activity in heavily pretreated patients with programmed cell death protein 1 or programmed death-ligand 1 blockade-resistant NSCLC.

Keywords

Atezolizumab; NSCLC; Radiation; TLR9 agonist; Vidutolimod.

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