TY - JOUR
T1 - Phase I dose-escalation study to determine the safety, tolerability, preliminary efficacy and pharmacokinetics of an intratumoral injection of tigilanol tiglate (EBC-46)
AU - Panizza, Benedict J.
AU - de Souza, Paul
AU - Cooper, Adam
AU - Roohullah, Aflah
AU - Karapetis, Christos S.
AU - Lickliter, Jason D.
PY - 2019/12
Y1 - 2019/12
N2 - Background: Tigilanol tiglate, a short-chain diterpene ester, is being developed as intratumoral treatment of a broad range of cancers. We conducted the first-in-human study of intratumoral tigilanol tiglate in patients with solid tumors. Methods: Tigilanol tiglate was administered in a multicentre, non randomized, single-arm study, with escalating doses beginning with 0·06 mg/m2 in tumors estimated to be at least twice the volume of injection (dose-escalation cohorts). Patients with smaller tumors were assigned to the local effects cohort and received the appropriate dose for tumor size. Findings: Twenty-two patients were enrolled. The maximum dose was 3·6 mg/m2 and the maximum tolerated dose was not reached. There was one report of dose-limiting toxicity (upper airway obstruction), two serious adverse events (upper airway obstruction and septicemia), 160 treatment-emergent adverse events, and no deaths. Injection site reactions in all tumors and tumor types occurred even at the lowest dose. Six of the 22 patients experienced a treatment response, with four of the six patients achieving complete response. Interpretation: Intratumoral tigilanol tiglate was generally well tolerated, the maximum tolerated dose was not reached, and clinical activity was observed in 9 tumor types including complete response in four patients. These results support the continued development of tigilanol tiglate for intratumoral administration. Funding: QBiotics Group Limited Brisbane, Queensland, Australia was the sponsor of the study.
AB - Background: Tigilanol tiglate, a short-chain diterpene ester, is being developed as intratumoral treatment of a broad range of cancers. We conducted the first-in-human study of intratumoral tigilanol tiglate in patients with solid tumors. Methods: Tigilanol tiglate was administered in a multicentre, non randomized, single-arm study, with escalating doses beginning with 0·06 mg/m2 in tumors estimated to be at least twice the volume of injection (dose-escalation cohorts). Patients with smaller tumors were assigned to the local effects cohort and received the appropriate dose for tumor size. Findings: Twenty-two patients were enrolled. The maximum dose was 3·6 mg/m2 and the maximum tolerated dose was not reached. There was one report of dose-limiting toxicity (upper airway obstruction), two serious adverse events (upper airway obstruction and septicemia), 160 treatment-emergent adverse events, and no deaths. Injection site reactions in all tumors and tumor types occurred even at the lowest dose. Six of the 22 patients experienced a treatment response, with four of the six patients achieving complete response. Interpretation: Intratumoral tigilanol tiglate was generally well tolerated, the maximum tolerated dose was not reached, and clinical activity was observed in 9 tumor types including complete response in four patients. These results support the continued development of tigilanol tiglate for intratumoral administration. Funding: QBiotics Group Limited Brisbane, Queensland, Australia was the sponsor of the study.
KW - Diterpene ester
KW - EBC-46
KW - Intratumoral
KW - Protein kinase C
KW - Tigilanol tiglate
UR - http://www.scopus.com/inward/record.url?scp=85076223829&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2019.11.037
DO - 10.1016/j.ebiom.2019.11.037
M3 - Article
C2 - 31810818
AN - SCOPUS:85076223829
SN - 2352-3964
VL - 50
SP - 433
EP - 441
JO - EBioMedicine
JF - EBioMedicine
ER -