MRTX-500 Phase 2 Trial: Sitravatinib With Nivolumab in Patients With Nonsquamous NSCLC Progressing On or After Checkpoint Inhibitor Therapy or Chemotherapy.
Antitumor activity
NSCLC
Nivolumab
Sitravatinib
Tyrosine kinase inhibitor
Journal
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
ISSN: 1556-1380
Titre abrégé: J Thorac Oncol
Pays: United States
ID NLM: 101274235
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
07
12
2022
revised:
16
02
2023
accepted:
21
02
2023
pmc-release:
01
07
2024
medline:
26
6
2023
pubmed:
27
2
2023
entrez:
26
2
2023
Statut:
ppublish
Résumé
Sitravatinib, a receptor tyrosine kinase inhibitor targeting TYRO3, AXL, MERTK receptors, and vascular epithelial growth factor receptor 2, can shift the tumor microenvironment toward an immunostimulatory state. Combining sitravatinib with checkpoint inhibitors (CPIs) may augment antitumor activity. The phase 2 MRTX-500 study evaluated sitravatinib (120 mg daily) with nivolumab (every 2 or 4 wk) in patients with advanced nonsquamous NSCLC who progressed on or after previous CPI (CPI-experienced) or chemotherapy (CPI-naive). CPI-experienced patients had a previous clinical benefit (PCB) (complete response, partial response, or stable disease for at least 12 weeks then disease progression) or no PCB (NPCB) from CPI. The primary end point was objective response rate (ORR); secondary objectives included safety and secondary efficacy end points. Overall, 124 CPI-experienced (NPCB, n = 35; PCB, n = 89) and 32 CPI-naive patients were treated. Investigator-assessed ORR was 11.4% in patients with NPCB, 16.9% with PCB, and 25.0% in CPI-naive. The median progression-free survival was 3.7, 5.6, and 7.1 months with NPCB, PCB, and CPI-naive, respectively; the median overall survival was 7.9 and 13.6 months with NPCB and PCB, respectively (not reached in CPI-naive patients; median follow-up 20.4 mo). Overall, (N = 156), any grade treatment-related adverse events (TRAEs) occurred in 93.6%; grade 3/4 in 58.3%. One grade 5 TRAE occurred in a CPI-naive patient. TRAEs led to treatment discontinuation in 14.1% and dose reduction or interruption in 42.9%. Biomarker analyses supported an immunostimulatory mechanism of action. Sitravatinib with nivolumab had a manageable safety profile. Although ORR was not met, this combination exhibited antitumor activity and encouraged survival in CPI-experienced patients with nonsquamous NSCLC.
Identifiants
pubmed: 36842467
pii: S1556-0864(23)00158-2
doi: 10.1016/j.jtho.2023.02.016
pmc: PMC10330304
mid: NIHMS1895208
pii:
doi:
Substances chimiques
Nivolumab
31YO63LBSN
sitravatinib
CWG62Q1VTB
Anilides
0
Types de publication
Clinical Trial, Phase II
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
907-921Subventions
Organisme : NCI NIH HHS
ID : K12 CA090625
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA133250
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016058
Pays : United States
Informations de copyright
Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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