Anti-CSF-1R emactuzumab in combination with anti-PD-L1 atezolizumab in advanced solid tumor patients naïve or experienced for immune checkpoint blockade

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  • dc.contributor.author Gómez-Roca, Carlos
  • dc.contributor.author Taus García, Álvaro
  • dc.contributor.author Martínez-García, Maria
  • dc.contributor.author Marabelle, Aurelien
  • dc.date.accessioned 2022-11-11T07:42:04Z
  • dc.date.available 2022-11-11T07:42:04Z
  • dc.date.issued 2022
  • dc.description.abstract Background: this phase 1b study (NCT02323191) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of colony-stimulating factor-1 receptor-blocking monoclonal antibody (mAb) emactuzumab in combination with the programmed cell death-1 ligand (PD-L1)-blocking mAb atezolizumab in patients with advanced solid tumors naïve or experienced for immune checkpoint blockers (ICBs). Methods: emactuzumab (500-1350 mg flat) and atezolizumab (1200 mg flat) were administered intravenously every 3 weeks. Dose escalation of emactuzumab was conducted using the 3+3 design up to the maximum tolerated dose (MTD) or optimal biological dose (OBD). Extension cohorts to evaluate pharmacodynamics and clinical activity were conducted in metastatic ICB-naive urothelial bladder cancer (UBC) and ICB-pretreated melanoma (MEL), non-small cell lung cancer (NSCLC) and UBC patients. Results: overall, 221 patients were treated. No MTD was reached and the OBD was determined at 1000 mg of emactuzumab in combination with 1200 mg of atezolizumab. Grade ≥3 treatment-related adverse events occurred in 25 (11.3%) patients of which fatigue and rash were the most common (14 patients (6.3%) each). The confirmed objective response rate (ORR) was 9.8% for ICB-naïve UBC, 12.5% for ICB-experienced NSCLC, 8.3% for ICB-experienced UBC and 5.6% for ICB-experienced MEL patients, respectively. Tumor biopsy analyses demonstrated increased activated CD8 +tumor infiltrating T lymphocytes (TILs) associated with clinical benefit in ICB-naïve UBC patients and less tumor-associated macrophage (TAM) reduction in ICB-experienced compared with ICB-naïve patients. Conclusion: emactuzumab in combination with atezolizumab demonstrated a manageable safety profile with increased fatigue and skin rash over usual atezolizumab monotherapy. A considerable ORR was particularly seen in ICB-experienced NSCLC patients. Increase ofCD8 +TILs under therapy appeared to be associated with persistence of a TAM subpopulation.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Gómez-Roca C, Cassier P, Zamarin D, Machiels JP, Luis Perez Gracia J, Stephen Hodi F, et al. Anti-CSF-1R emactuzumab in combination with anti-PD-L1 atezolizumab in advanced solid tumor patients naïve or experienced for immune checkpoint blockade. J Immunother Cancer. 2022 May; 10(5): e004076. DOI: 10.1136/jitc-2021-004076
  • dc.identifier.doi http://dx.doi.org/10.1136/jitc-2021-004076
  • dc.identifier.issn 2051-1426
  • dc.identifier.uri http://hdl.handle.net/10230/54798
  • dc.language.iso eng
  • dc.publisher BMJ Publishing Group
  • dc.rights © Gómez-Roca C, Cassier P, Zamarin D, Machiels JP, Luis Perez Gracia J, Stephen Hodi F, et al. 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.keyword Clinical Trials as Topic
  • dc.subject.keyword Drug Therapy, Combination
  • dc.subject.keyword Immunotherapy
  • dc.subject.keyword Macrophages
  • dc.subject.keyword T-Lymphocytes
  • dc.title Anti-CSF-1R emactuzumab in combination with anti-PD-L1 atezolizumab in advanced solid tumor patients naïve or experienced for immune checkpoint blockade
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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