The primary objective of this study is to evaluate the tolerability and safety profile of farletuzumab ecteribulin in participants with solid tumors.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
82
Part 1: farletuzumab ecteribulin intravenous (IV) infusion administered every 3 weeks starting at a 0.3 mg/kg dose and successively increasing doses until DLT. Part 2: farletuzumab ecteribulin administered IV every 3 weeks at a dose determined in Part 1 until any of the criteria for discontinuation are met.
Eisai Trial Site 5
Matsuyama, Ehime, Japan
Eisai Trial Site 6
Kurume, Fukuoka, Japan
Eisai Trial Site 8
Sapporo, Hokkaido, Japan
Eisai Trial Site 4
Akashi, Hyōgo, Japan
Part 1: Number of participants with dose-limiting toxicities (DLTs)
DLTs are defined as the following occurring in Cycle 1 for which a causal relationship with study drug cannot be ruled out: febrile neutropenia, Grade 4 neutropenia persisting for more than 7 days, or neutropenia requiring hematopoietic stimulating agents, Grade 4 thrombocytopenia, or thrombocytopenia requiring platelet transfusion, Grade 4 anemia, or anemia requiring blood transfusion, Grade 3 non-hematological toxicity (except abnormal clinical laboratory values of no clinical significance, any events which can be managed and controlled to Grade 2 or less by maximal medical management, infusion reactions of Grade 3 or higher are NOT considered DLTs because they are stochastic and idiosyncratic events, not related to dose), Grade 4 non-hematological toxicity, and/or when the second treatment with farletuzumab ecteribulin is postponed more than 14 days from the scheduled day due to toxicity. DLTs will be determined by discussion between the investigator, sponsor, and medical expert.
Time frame: At the end of Cycle 1 (21 days)
Part 1 and Part 2: Number of participants with adverse events (AEs), adverse events of interest (AEIs), and serious adverse events (SAEs)
Time frame: Up to 50 months
Number of participants with any clinically significant clinical laboratory test value
Clinical significance will be determined by the Investigator.
Time frame: Up to 50 months
Number of participants with any clinically significant vital sign value
Clinical significance will be determined by the Investigator.
Time frame: Up to 50 months
Change from Baseline in arterial oxygen saturation
Time frame: Baseline; up to 50 months
Change from Baseline in body weight
Time frame: Baseline; up to 50 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Eisai Trial Site 7
Niigata, Niigata, Japan
Eisai Trial Site 3
Hidaka, Saitama, Japan
Eisai Trial Site 9
Sunto-gun, Shizuoka, Japan
Eisai Trial Site 1
Chuo-ku, Tokyo, Japan
Eisai Trial Site 10
Koto-Ku, Tokyo, Japan
Eisai Trial Site 2
Koto-ku, Tokyo, Japan
Number of participants with any clinically significant 12-lead electrocardiogram (ECG) value
Clinical significance will be determined by the Investigator.
Time frame: Up to 50 months
Change from Baseline in the performance status (PS) score established by the Eastern Cooperative Oncology Group (ECOG)
Time frame: Baseline; up to 50 months
Change from Baseline in serum anti-drug antibody (ADA) titer
Time frame: Baseline; up to 50 months
Part 1: Maximum Tolerated Dose (MTD) of Farletuzumab Ecteribulin
The MTD will be selected as the dose with the smallest difference between the target DLT rate of 25% and an estimate of DLT rate based on the posterior distribution of DLT rate for each dose.
Time frame: 21 days following each dose level of farletuzumab ecteribulin (up to a maximum of 50 months)
Part 1 and Part 2: Maximum observed serum concentration (Cmax) of Farletuzumab Ecteribulin
Cmax is the maximum serum concentration of farletuzumab ecteribulin after administration of the drug.
Time frame: Predose; end of infusion; 0.5, 1, 2, 4, and 24 hours post infusion on Day 1; on Days 4, 8, and 15; and the discontinuation and last observation visit (up to 50 months)
Part 1 and Part 2: Maximum serum concentration of total antibody
Time frame: Predose; end of infusion; 0.5, 1, 2, 4, and 24 hours post infusion on Day 1; on Days 4, 8, and 15; and the discontinuation and last observation visit (up to 50 months)
Part 1 and Part 2: Plasma concentration of free eribulin
Time frame: Predose; end of infusion; 0.5, 1, 2, 4, and 24 hours post infusion on Day 1; on Days 4, 8, and 15; and the discontinuation and last observation visit (up to 50 months)
Recommended dose (RD) of farletuzumab ecteribulin for future studies
The RD will be determined based on the MTD, efficacy, and safety data in Part 1 and Part 2.
Time frame: From the date of screening until the last observation visit (up to 50 months)
Part 1 and Part 2: Best overall response (BOR)
BOR was based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). BORs are complete response (CR), partial response (PR), stable disease (SD), progression of disease (PD), and not evaluable (NE), where SD has to be achieved at ≥5 weeks after the first dose. CR or PR in Part 1 of this study requires no confirmation of the next response at ≥4 weeks. CR or PR in Part 2 of this study requires confirmation of the next response at ≥4 weeks.
Time frame: From the date of screening until the last observation visit (up to 50 months)
Part 1 and Part 2: Overall response rate (ORR)
ORR is defined as the percentage of participants with BOR of CR or PR.
Time frame: From the date of screening until the last observation visit (up to 50 months)
Part 1 and Part 2: Disease control rate (DCR)
DCR is defined as the percentage of participants with BOR of CR, PR, or SD.
Time frame: From the date of screening until the last observation visit (up to 50 months)
Part 1 and Part 2: Clinical benefit rate (CBR)
CBR is defined as the percentage of participants with BOR of CR, PR or durable (SD) (duration of SD ≥ 23 weeks).
Time frame: From the date of screening until the last observation visit (up to 50 months)
Part 2: Duration of Response (DOR)
DOR is defined as the time from the first documentation of CR or PR to the first documented date of event (disease progression or death from any cause, whichever occurs first).
Time frame: From the date of screening until the last observation visit (up to 50 months)
Part 2: Progression-free survival (PFS)
PFS is defined as the time from the date of the first dose of study drug to the first documented date of event (disease progression or death from any cause, whichever occurs first).
Time frame: From the date of screening until disease progression or death (up to 50 months)
Part 2: Overall Survival (OS)
OS is defined as the time from the date of the first dose to the date of death from any cause. For participants who are alive or unknown, OS is censored as the date of the last known alive date or the date of data cut off, whichever comes first.
Time frame: From the date of screening until the last observation visit (up to 50 months)