Phase 1 study of the safety, pharmacokinetics, and preliminary efficacy of CA102N as monotherapy and in combination with trifluridine-tipiracil in patients with locally advanced or metastatic solid tumors.
CA102N
Clinical trials
Colorectal cancer
Phase 1
Trifluridine-tipiracil
Journal
Investigational new drugs
ISSN: 1573-0646
Titre abrégé: Invest New Drugs
Pays: United States
ID NLM: 8309330
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
26
08
2022
accepted:
22
09
2022
pubmed:
5
11
2022
medline:
24
3
2023
entrez:
4
11
2022
Statut:
ppublish
Résumé
CA102N is a covalently bound conjugate of modified nimesulide (Nim) and NaHA, the sodium salt of hyaluronic acid (HA). HA is a natural ligand of cluster of differentiation 44 (CD44), which is over-expressed in colorectal cancer (CRC). CA102N is designed to deliver nimesulide directly to the tumor via the interaction of HA and CD44. A Phase 1, 2-part (dose escalation, dose expansion), non-randomized, open-label, first-in-human study of CA102N, as monotherapy and in combination with trifluridine-tipiracil, was conducted in patients with locally advanced or metastatic solid tumors. The CA102N doses evaluated were 0.36 mg/kg, 0.54 mg/kg, and 0.72 mg/kg Nim equivalent. The primary endpoints were dose-limiting toxicities (DLTs) in Cycle 1 as well as serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs) throughout the study; secondary endpoints were pharmacodynamics parameters, objective tumor response, and urinary pharmacodynamics markers of target inhibition. Between April 2019 and October 2021, 37 patients were enrolled in 3 US centers. No DLTs were observed in Part 1, and 0.72 mg/kg Nim equivalent was the dose selected for Part 2. In total, 52 TEAEs in 18 patients were CA102N-related; 4 (in 3 patients) were ≥ Grade 3. Exploratory analysis in the dose expansion cohort revealed a median progression-free survival of 3.7 (1.0, 6.77) months. Based on this study, CA102N as monotherapy or in combination with trifluridine-tipiracil, was safe and well-tolerated at the recommended Phase 2 dose of 0.72 mg/kg Nim equivalent in patients with locally advanced or metastatic solid tumors. Preliminary evidence of antitumor activity in CRC warrants further clinical development. (ClinicalTrials.gov registration number: NCT03616574. Registration date: August 6, 2018).
Identifiants
pubmed: 36331676
doi: 10.1007/s10637-022-01308-5
pii: 10.1007/s10637-022-01308-5
doi:
Substances chimiques
nimesulide
V4TKW1454M
tipiracil
NGO10K751P
Trifluridine
RMW9V5RW38
Sulfonamides
0
Drug Combinations
0
Cyclooxygenase 2 Inhibitors
0
Hyaluronic Acid
9004-61-9
Banques de données
ClinicalTrials.gov
['NCT03616574']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
25-34Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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