Phase I/II Study of the Mesothelin-targeted Immunotoxin LMB-100 with Nab-Paclitaxel for Patients with Advanced Pancreatic Adenocarcinoma.
Adenocarcinoma
/ drug therapy
Adult
Aged
Albumins
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Drug Administration Schedule
Female
GPI-Linked Proteins
/ antagonists & inhibitors
Humans
Immunoconjugates
/ administration & dosage
Male
Maximum Tolerated Dose
Mesothelin
Middle Aged
Molecular Targeted Therapy
Paclitaxel
/ administration & dosage
Pancreatic Neoplasms
/ drug therapy
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 02 2020
15 02 2020
Historique:
received:
06
08
2019
revised:
08
10
2019
accepted:
25
11
2019
pubmed:
4
12
2019
medline:
18
11
2020
entrez:
4
12
2019
Statut:
ppublish
Résumé
LMB-100 is a recombinant immunotoxin (iTox) consisting of a mesothelin-binding Fab for targeting and a modified Patients ( Fourteen patients were treated on the dose escalation and an additional six in the phase II expansion. MTD of 65 μg/kg was established for the combination. Dose-limiting toxicity resulting from capillary leak syndrome (CLS) was seen in two of five patients treated at 100 μg/kg and one of six evaluable phase I patients receiving the MTD. Severity of CLS was associated with increases in apoptotic circulating endothelial cells. LMB-100 exposure was unaffected by anti-LMB-100 antibody formation in five of 13 patients during cycle 2. Seven of 17 evaluable patients experienced >50% decrease in CA 19-9, including three with previous exposure to nab-paclitaxel. One patient developed an objective partial response. Patients with biomarker responses had higher tumor mesothelin expression. Although clinical activity was observed, the combination was not well tolerated and alternative drug combinations with LMB-100 will be pursued.
Identifiants
pubmed: 31792036
pii: 1078-0432.CCR-19-2586
doi: 10.1158/1078-0432.CCR-19-2586
pmc: PMC8268773
mid: NIHMS1706785
doi:
Substances chimiques
130-nm albumin-bound paclitaxel
0
Albumins
0
GPI-Linked Proteins
0
Immunoconjugates
0
LMB-100
D6AT024T4P
Mesothelin
J27WDC343N
Paclitaxel
P88XT4IS4D
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
828-836Subventions
Organisme : Intramural NIH HHS
ID : ZIA BC010020
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA BC011652
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
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