Dose Escalation Data from the Phase 1 Study of the Liposomal Formulation of Eribulin (E7389-LF) in Japanese Patients with Advanced Solid Tumors.

Abstract

PURPOSE:

We report the dose-escalation part of a phase I study of liposomal eribulin (E7389-LF) in Japanese patients with advanced solid tumors and no alternative standard therapy.

PATIENTS AND METHODS:

Patients ≥20 years old were enrolled. E7389-LF doses of 1.0 to 1.5 mg/m2 once every two weeks (Q2W) or 1.0 to 2.5 mg/m2 once every three weeks (Q3W) were planned. The primary objective was to determine the MTD by evaluating dose-limiting toxicities (DLT). Secondary objectives included safety/tolerability assessments, objective response rate (ORR), and progression-free survival; serum biomarker assessment was an exploratory objective.

RESULTS:

Twenty-one patients were enrolled and treated; 12 in the Q3W group (1.0 mg/m2, n = 3; 1.5 mg/m2, n = 3; 2.0 mg/m2, n = 6) and 9 in the Q2W group (1.0 mg/m2, n=3; 1.5 mg/m2, n = 6). The Q3W and Q2W MTDs were 2.0 mg/m2 and 1.5 mg/m2, respectively. One patient receiving 2.0 mg/m2 Q3W had a DLT of grade 3 febrile neutropenia. The most common grade 3 treatment-emergent adverse events were neutropenia (66.7% in Q3W and Q2W) and leukopenia (Q3W, 58.3%; Q2W, 33.3%). One patient in the Q3W group (2.0 mg/m2) and 3 in the Q2W group (1.0 mg/m2, n = 1; 1.5 mg/m2, n = 2) achieved a partial response [overall ORR, 19.0%; 95% confidence interval (CI), 5.4-41.9]. Endothelial [TEK receptor tyrosine kinase (TEK), intercellular adhesion molecule 1 (ICAM1), vascular endothelial growth factor receptor 3 (VEGFR3), platelet/endothelial cell adhesion molecule 1 (PECAM1)], vasculature (collagen IV), and immune-related [interferon gamma (IFNγ), C-X-C motif chemokine ligand 11 (CXCL11), C-X-C motif chemokine ligand 10 (CXCL10)] biomarker levels were increased.

CONCLUSIONS:

E7389-LF was well tolerated at 2.0 mg/m2 Q3W and 1.5 mg/m2 Q2W. Considering the toxicity profile of both regimens, the recommended dose was 2.0 mg/m2 Q3W. Expansion cohorts are ongoing.

• Authors: Jun Sato, Toshio Shimizu, Takafumi Koyama, Satoru Iwasa, Akihiko Shimomura, Shunsuke Kondo, Shigehisa Kitano, Kan Yonemori, Yutaka Fujiwara, Kenji Tamura, Takuya Suzuki, Takao Takase, Reiko Nagai, Kohei Yamaguchi, Taro Semba, Zi-Ming Zhao, Min Ren, Noboru Yamamoto
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 28 Issue 9 Pg. 1783-1791 (05 02 2022) ISSN: 1557-3265 [Electronic] United States
• PMID: 35180771 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2022 The Authors; Published by the American Association for Cancer Research.

Chemical References

• Biomarkers
• Chemokines
• Furans
• Ketones
• Ligands
• Liposomes
• Vascular Endothelial Growth Factor A
• eribulin

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols
• Biomarkers
• Chemokines
• Dose-Response Relationship, Drug
• Furans
• Humans
• Japan
• Ketones
• Ligands
• Liposomes
• Maximum Tolerated Dose
• Neoplasms (pathology)
• Vascular Endothelial Growth Factor A
• Young Adult