Abstract 583P
Background
In the dose-escalation part of a phase I study, E7389-LF 2.0 mg/m2 tri-weekly (Q3W) was determined as the recommended dosing regimen, administered using a 4-step infusion rate and with a 2-drug premedication regimen (a corticosteroid and an antihistamine) for hypersensitivity reaction (HSR). In the expansion part of the study, further safety of the regimen was evaluated.
Methods
Patients (pts) with adenoid cystic carcinoma (ACC), gastric cancer (GC), esophageal cancer (EGC), and small cell lung cancer (SCLC), for which no alternative standard therapy exists, were enrolled in the expansion part (n≈10 per group). E7389-LF 2.0 mg/m2 was administered Q3W to pts with ACC using a 4-step infusion rate with 2-drug premedication, and to the others using a 2-step infusion rate, with 2-drug, 1-drug, or no premedication. Prophylactic usage of peg-filgrastim (peg-G-CSF) was allowed. Preventive effects against HSR from infusion steps or premedication, and of neutropenia by peg-G-CSF, were assessed.
Results
43 Pts (12 ACC; 10 GC; 11 EGC; 10 SCLC) were enrolled. The median age was 60.9 yrs and 67.4% had ECOG-PS 0. Partial response was observed in 5 pts (2 ACC; 2 GC; 1 EGC). Stable disease was observed in 26 pts (9 ACC; 6 GC; 5 EGC; 6 SCLC). In all pts, grade ≥3 AEs included neutropenia (53.5%) and leukopenia (34.9%). Grade ≥3 HSR was not seen. In cycle 1, rates of grade ≥3 neutropenia and febrile neutropenia (FN) were lower in pts receiving peg-G-CSF. There was no clear difference in the incidence of grade 1-2 HSRs across the infusion steps and premedication groups (Table). Table: 583P
| Peg-G-CSF | Grade ≥3 Neutropenia and FN | Incidence in Cycle 1, n (%) | |
| Yes (27 pts) | Neutropenia | 3 (11.1) | |
| FN | 1 (3.7) | ||
| No (16 pts) | Neutropenia | 13 (81.3) | |
| FN | 2 (12.5) | ||
| # of Infusion Steps | Corticosteroid | Antihistamine | # HSR in Cycle 1 Pts |
| 4a | Yes | Yes | 1/12 (grade 1) |
| 2b | Yes | Yes | 0/10 |
| No | Yes | 2/10 (grade 1 and 2) | |
| No | No | 2/10 (both grade 2) |
a4-Step E7389-LF infusion rate: 0.005, 0.01, and 0.02 mg/min (for ≥10 min in each step); then ≤0.2 mg/min. b2-Step E7389-LF infusion rate: 0.01 mg/min (for ≥10 min); then 0.1 mg/min.
Conclusions
E7389-LF 2.0 mg/m2 Q3W was well tolerated and showed activity in several tumor types. Lower rates of neutropenia and FN were seen in pts treated with prophylactic Peg-G-CSF. A reduced number of infusion steps did not increase the incidence of HSRs. However, the necessity of premedication is unclear and further investigation is needed.
Clinical trial identification
NCT03207672.
Editorial acknowledgement
Editorial support was provided by Oxford PharmaGenesis, Newtown, PA and was funded by Eisai Inc., Woodcliff Lake, NJ, USA.
Legal entity responsible for the study
Eisai Co., Ltd., Tokyo, Japan.
Funding
This study was funded by Eisai Co., Ltd., Tokyo, Japan.
Disclosure
S. Iwasa: Research grant/Funding (self), Research grant/Funding (institution): Eisai. S. Takahashi: Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): Eisai; Honoraria (self), Research grant/Funding (self): Ono pharmaceutical; Honoraria (self), Research grant/Funding (self): Bristol-Myers-Squib; Honoraria (self), Research grant/Funding (self): Chugai; Honoraria (self), Research grant/Funding (self): MSD; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self), Research grant/Funding (self): Taiho; Honoraria (self), Research grant/Funding (self): Bayer; Honoraria (self), Research grant/Funding (self): AstraZenca. K. Kato: Research grant/Funding (self): MSD; Research grant/Funding (self): ONO; Research grant/Funding (self): BMS; Research grant/Funding (self): Shionogi; Research grant/Funding (self): Beigene; Research grant/Funding (self): Merck Biio. K. Shitara: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self): Yakult; Advisory/Consultancy, Research grant/Funding (institution): Astellas; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Takeda; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Ono; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Taiho; Advisory/Consultancy: GlaxoSmithKline; Research grant/Funding (institution): Sumoitomo Dainippon; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Chugai; Research grant/Funding (institution): Medi Science. Y. Sato: Honoraria (self), lecture fees: ONO Pharmaceutical Co., LTD.; Honoraria (self), lecture fees: Bristol-Myers Squibb Company; Honoraria (self), lecture fees: Taiho Pharmaceutical Co., LTD.; Honoraria (self), lecture fees: MSD K.K.. H. Horinouchi: Research grant/Funding (self), Research grant/Funding (institution): Eisai; Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Genomic Health; Honoraria (self), Research grant/Funding (institution): Lilly; Honoraria (self), Research grant/Funding (institution): Ono. M. Tahara: Research grant/Funding (self), Research grant/Funding (institution): Eisai; Honoraria (self): Merck Serono; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): Rakuten Medical; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Bayer; Honoraria (self): LOXO. T. Suzuki: Full/Part-time employment: Eisai Co., Ltd. T. Takase: Full/Part-time employment: Eisai Co., Ltd. R. Matsunaga: Full/Part-time employment: Eisai Co., Ltd. T. Mukohara: Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Sysmex; Honoraria (self), Research grant/Funding (institution), lecture fees: Eisai; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution), lecture fees: Novartis; Research grant/Funding (institution): Sanofi; Honoraria (self), Research grant/Funding (institution), lecture fees: Chugai; Honoraria (self), lecture fees: Eli Lilly; Honoraria (self), lecture fees: AstraZeneca; Honoraria (self), lecture fees: Kyowa-Kirin. All other authors have declared no conflicts of interest.