Table 1

Selected studies of TAM receptor inhibitors combined with CPI therapies in CPI-resistant NSCLC

Treatment/targetsSponsorClinicalTrials.gov identifierPhasePCDnTreatment regimen and latest results
Sitravatinib
Tyro3, Axl, MerTK, VEGFR2, PDGFR, KIT, FLT3, MET, RET
Mirati Therapeutics, Inc.NCT02954991205/2021206*Sitravatinib + nivolumab arm
After a median follow-up of 28 mo, among 68 pts with prior clinical benefit from CPI:96
  • ORR: 16% (including 2 CRs)

  • mOS: 15 mo (95% CI 9.3 to 21.1)

  • 1-year and 2-year OS rates: 56% and 32%, respectively

  • mPFS: 6 months

Mirati Therapeutics, Inc. and Bristol-Myers SquibbNCT03906071309/2022532†SAPPHIRE:97 Sitravatinib + nivolumab versus docetaxel
BeiGeneNCT04921358306/2024420†Sitravatinib + tislelizumab versus docetaxel
Cabozantinib
Tyro3, Axl, MerTK, VEGFR2, KIT, FLT3, MET, RET
ExelixisNCT031709601–212/20211732†COSMIC-021: Cabozantinib + atezolizumab88
After a median follow-up of 8.9 months (n=30):
  • ORR: 23% (all PRs including three pts refractory to prior CPI)

  • DCR: 83%

Roche/ExelixisNCT04471428309/2022366*CONTACT-01: Cabozantinib + atezolizumab vs docetaxel
Bemcentinib
Axl
BerGenBio/ Merck Sharp & DohmeNCT03184571209/2022106†Bemcentinib + pembrolizumab106 114
After a median treatment duration of 8.9 weeks, among CPI-refractory pts (Cohort B) with cAxl-positive tumors (n=7):
  • ORR: 14% (1 pt with PR)

  • CBR: 86% (6 pts)

  • mPFS: 4.73 mo (HR 0.22; 95% CI 0.04 to 1.26; p=0.066)

BA3011
Axl
BioAltaNCT04681131212/2022240†BA3011 monotherapy
BA3011 + PD-1 inhibitor
INCB081776
Axl, MerTK
Incyte CorporationNCT03522142109/2022140†INCB081776 + retifanlimab (INCMGA00012)89
PF-07265807/ARRAY-067
Axl, MerTK
PfizerNCT04458259101/2024115†PF-07265807 + sasanlimab arm109
  • *Actual enrolment.

  • †Estimated enrolment.

  • CBR, clinical benefit rate; CPI, checkpoint inhibitor; CR, complete response; DCR, disease control rate; FLT3, FMS-like tyrosine kinase; KIT, KIT proto-oncogene RTK; MET, hepatocyte growth factor receptor; mOS, median overall survival; mPFS, median progression-free survival; NSCLC, non-small-cell lung cancer; ORR, objective response rate; OS, overall survival; PCD, primary completion date; PDGFR, platelet-derived growth factor receptor; PR, partial response; pts, patients; RET, rearranged during transfection; TAM, Tyro3, Axl, MerTK; VEGFR2, vascular endothelial growth factor receptor 2.