PMID- 33507454
OWN - NLM
STAT- MEDLINE
DCOM- 20220202
LR  - 20220202
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Linking)
VI  - 39
IP  - 4
DP  - 2021 Aug
TI  - A phase 1b trial of the CXCR4 inhibitor mavorixafor and nivolumab in advanced 
      renal cell carcinoma patients with no prior response to nivolumab monotherapy.
PG  - 1019-1027
LID - 10.1007/s10637-020-01058-2 [doi]
AB  - Background The CXCR4 chemokine receptor promotes tumor survival through 
      mechanisms that include suppressing antitumor immune responses. Mavorixafor 
      (X4P-001) is an oral, selective, allosteric CXCR4 inhibitor that decreases the 
      recruitment of immunosuppressive cells into the tumor microenvironment and 
      increases activated cytotoxic Tcell infiltration. Methods Patients with 
      metastatic clear cell renal cell carcinoma (ccRCC) unresponsive to nivolumab 
      monotherapy received oral mavorixafor 400 mg daily plus 240 mg intravenous 
      nivolumab every 2 weeks. Results Nine patients were enrolled, median age 
      65 years. At baseline 4 had progressive disease (PD) and 5 had stable disease 
      (SD). One of 5 patients with SD at study entry on prior nivolumab monotherapy had 
      a partial response (PR) on combination treatment; all 4 patients with PD at study 
      entry had a best response of SD with the combination treatment (median duration: 
      6.7 months; range: 3.7-14.7). Four patients discontinued therapy due to 
      treatment-related adverse events (AEs). Grade >/= 3 drug-related AEs were elevated 
      alanine and aspartate aminotransferase (2 patients each); and autoimmune 
      hepatitis, chronic kidney disease, increased lipase, maculopapular rash, and 
      mucosal inflammation (1 patient each). A robust increase in levels of chemokine 
      (C-X-C motif) ligand 9 CXCL9 on mavorixafor appeared to correlate with clinical 
      benefit. Conclusions The CXCR4 inhibition mediated by mavorixafor, in combination 
      with PD-1 blockade to enhance antitumor immune responses in patients unresponsive 
      to checkpoint inhibitor monotherapy, is worthy of further study. Mavorixafor and 
      nivolumab combination therapy in patients with advanced ccRCC demonstrated 
      potential antitumor activity and a manageable safety profile.Trial registration: 
      ClinicalTrials.gov identifier: NCT02923531. Date of registration: October 04, 
      2016.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC part of Springer Nature.
FAU - Choueiri, Toni K
AU  - Choueiri TK
AUID- ORCID: 0000-0002-9201-3217
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, 
      Boston, MA, 02215, USA. Toni_Choueiri@DFCI.HARVARD.EDU.
FAU - Atkins, Michael B
AU  - Atkins MB
AD  - Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC, USA.
FAU - Rose, Tracy L
AU  - Rose TL
AD  - Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.
FAU - Alter, Robert S
AU  - Alter RS
AD  - John Theurer Cancer Center Hackensack UMC, Hackensack, NJ, USA.
FAU - Ju, Yawen
AU  - Ju Y
AD  - X4 Pharmaceuticals, Cambridge, MA, USA.
FAU - Niland, Katie
AU  - Niland K
AD  - X4 Pharmaceuticals, Cambridge, MA, USA.
FAU - Wang, Yan
AU  - Wang Y
AD  - X4 Pharmaceuticals, Cambridge, MA, USA.
FAU - Arbeit, Robert
AU  - Arbeit R
AD  - X4 Pharmaceuticals, Cambridge, MA, USA.
FAU - Parasuraman, Sudha
AU  - Parasuraman S
AD  - X4 Pharmaceuticals, Cambridge, MA, USA.
FAU - Gan, Lu
AU  - Gan L
AD  - X4 Pharmaceuticals, Cambridge, MA, USA.
FAU - McDermott, David F
AU  - McDermott DF
AD  - Beth Israel Deaconess Medical Center, Boston, MA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02923531
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210128
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Aminoquinolines)
RN  - 0 (Benzimidazoles)
RN  - 0 (Butylamines)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Receptors, CXCR4)
RN  - 0G9LGB5O2W (mavorixafor)
RN  - 31YO63LBSN (Nivolumab)
SB  - IM
MH  - Aged
MH  - Aminoquinolines/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects/pharmacology
MH  - Benzimidazoles/administration & dosage
MH  - Butylamines/administration & dosage
MH  - Carcinoma, Renal Cell/*drug therapy/pathology
MH  - Female
MH  - Humans
MH  - Kidney Neoplasms/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
MH  - Nivolumab/administration & dosage
MH  - Receptors, CXCR4/antagonists & inhibitors
MH  - Treatment Outcome
MH  - Tumor Microenvironment
OTO - NOTNLM
OT  - CXCR4
OT  - Immune therapy
OT  - Mavorixafor
OT  - Nivolumab
OT  - Renal cell carcinoma
OT  - Tumor microenvironment
OT  - X4P-001
EDAT- 2021/01/29 06:00
MHDA- 2022/02/03 06:00
CRDT- 2021/01/28 12:16
PHST- 2020/11/19 00:00 [received]
PHST- 2020/12/20 00:00 [accepted]
PHST- 2021/01/29 06:00 [pubmed]
PHST- 2022/02/03 06:00 [medline]
PHST- 2021/01/28 12:16 [entrez]
AID - 10.1007/s10637-020-01058-2 [pii]
AID - 10.1007/s10637-020-01058-2 [doi]
PST - ppublish
SO  - Invest New Drugs. 2021 Aug;39(4):1019-1027. doi: 10.1007/s10637-020-01058-2. Epub 
      2021 Jan 28.