A Single-arm Phase II Study Combining NLG207, a Nanoparticle Camptothecin, with Enzalutamide in Advanced Metastatic Castration-resistant Prostate Cancer Post-Enzalutamide.
NLG207
enzalutamide
metastatic castration-resistant prostate cancer (mCRPC)
nanoparticle
noninfective cystitis
Journal
The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837
Informations de publication
Date de publication:
02 09 2022
02 09 2022
Historique:
received:
28
03
2022
accepted:
06
04
2022
pubmed:
1
6
2022
medline:
9
9
2022
entrez:
31
5
2022
Statut:
ppublish
Résumé
Despite the clinical efficacy of enzalutamide monotherapy in patients with advanced prostate cancer, therapeutic resistance and disease progression are inevitable. We proposed a study to evaluate NLG207, a nanoparticle-drug conjugate (NDC) of the potent topoisomerase I inhibitor camptothecin, in combination with enzalutamide, in patients with metastatic castration-resistant prostate cancer (mCRPC) following progression on enzalutamide. This was a single-arm, optimal two-stage, phase II study to evaluate the efficacy of NLG207 in combination with enzalutamide in patients with mCRPC who received prior enzalutamide. A lead-in dose escalation evaluated the recommended phase 2 dose of NLG207 in combination with enzalutamide. Patients received NLG207 via IV infusion every 2 weeks and enzalutamide 160 mg orally once daily. Between March 2019 and June 2021, four patients were accrued to the lead-in dose escalation. Two of the four patients were evaluable and both experienced DLTs at the NLG207 12 mg/m2 dose level; one DLT was related to a dose delay for noninfective cystitis and myelosuppression, the other a grade 3 noninfective cystitis. Further evaluation of NLG207 in combination with enzalutamide was halted and the study was ultimately terminated. PSA declines from baseline were observed in two patients. NLG207 12 mg/m2 in combination with enzalutamide was not well tolerated in patients with mCRPC following several lines of the standard of care therapy. NCT03531827.
Sections du résumé
BACKGROUND
Despite the clinical efficacy of enzalutamide monotherapy in patients with advanced prostate cancer, therapeutic resistance and disease progression are inevitable. We proposed a study to evaluate NLG207, a nanoparticle-drug conjugate (NDC) of the potent topoisomerase I inhibitor camptothecin, in combination with enzalutamide, in patients with metastatic castration-resistant prostate cancer (mCRPC) following progression on enzalutamide.
METHODS
This was a single-arm, optimal two-stage, phase II study to evaluate the efficacy of NLG207 in combination with enzalutamide in patients with mCRPC who received prior enzalutamide. A lead-in dose escalation evaluated the recommended phase 2 dose of NLG207 in combination with enzalutamide. Patients received NLG207 via IV infusion every 2 weeks and enzalutamide 160 mg orally once daily.
RESULTS
Between March 2019 and June 2021, four patients were accrued to the lead-in dose escalation. Two of the four patients were evaluable and both experienced DLTs at the NLG207 12 mg/m2 dose level; one DLT was related to a dose delay for noninfective cystitis and myelosuppression, the other a grade 3 noninfective cystitis. Further evaluation of NLG207 in combination with enzalutamide was halted and the study was ultimately terminated. PSA declines from baseline were observed in two patients.
CONCLUSION
NLG207 12 mg/m2 in combination with enzalutamide was not well tolerated in patients with mCRPC following several lines of the standard of care therapy.
CLINICALTRIALS.GOV IDENTIFIER
NCT03531827.
Identifiants
pubmed: 35640474
pii: 6594964
doi: 10.1093/oncolo/oyac100
pmc: PMC9438911
doi:
Substances chimiques
Cyclodextrins
0
IT-101
0
Nitriles
0
Camptothecin
XT3Z54Z28A
Banques de données
ClinicalTrials.gov
['NCT03531827']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
718-e694Subventions
Organisme : Intramural NIH HHS
ID : Z01 BC010547
Pays : United States
Organisme : NIH HHS
ID : ZIA BC 010547
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA BC010547
Pays : United States
Informations de copyright
Published by Oxford University Press 2022. The data published online to support this summary are the property of the authors. Please contact the authors about reuse rights of the original data.
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