E7389-701

Eisai Inc.

155 Tice Boulevard Woodcliff Lake, New Jersey, United States, 07677

Eisai Medical Information, Eisai Inc., 01 888-274-2378, esi_oncmedinfo@eisai.com

Eisai Medical Information, Eisai Inc., 01 888-274-2378, esi_oncmedinfo@eisai.com

No

No

No

Final

18 Mar 2015

No

Yes

18 Mar 2015

No

The primary objective of Phase 1b was to define the maximum tolerated dose (MTD)/dose recommended for Phase II of eribulin mesylate, administered in combination with pemetrexed in subjects with nonsquamous, non-small cell lung cancer (NSCLC), previously treated with 1 cytotoxic chemotherapy regimen for stage IIIB or IV disease. The primary objective of Phase 2 was to evaluate the safety and tolerability of multiple doses of eribulin administered in combination with pemetrexed, compared with pemetrexed alone as second-line therapy in subjects with advanced nonsquamous NSCLC.

This study was conducted in accordance with standard operating procedures (SOPs) of the sponsor (or designee), which are designed to ensure adherence to Good Clinical Practice (GCP) guidelines as required by the following: - Principles of the World Medical Association Declaration of Helsinki (World Medical Association, 2008) - International Council on Harmonisation (ICH) E6 Guideline for GCP (CPMP/ICH/135/95) of the European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use - Title 21 of the United States (US) Code of Federal Regulations (US 21 CFR) regarding clinical studies, including Part 50 and Part 56 concerning informed subject consent and Institutional Review Board (IRB) regulations and applicable sections of US 21 CFR Part 312 - European Good Clinical Practice Directive 2005/28/EC and Clinical Trial Directive 2001/20/EC for studies conducted within any European Union (EU) country. All suspected unexpected serious adverse reactions were reported, as required, to the Competent Authorities of all involved EU member states. - Article 14, Paragraph 3, and Article 80-2 of the Pharmaceutical Affairs Law (Law No. 145, 1960) for studies conducted in Japan, in addition to Japan’s GCP Subject Information and Informed Consent.

10 Jun 2010

No

No

Ukraine: 39

United States: 16

Czechia: 25

Germany: 6

Italy: 12

98

43

0

0

0

0

0

0

69

29

0

Phase 1b and Phase 2 (overall) (overall period)

Randomised - controlled

Yes

Eribulin Mesilate

E7389

Infusion

Intravenous use

Subjects received eribulin mesylate 0.9 mg/m^2, IV infusion in combination with pemetrexed (500 mg/m^2) on Day 1 of a 21 day treatment cycle.

Eribulin Mesilate

E7389

Infusion

Intravenous use

Subjects received eribulin mesylate 1.4 mg/m^2, IV infusion in combination with pemetrexed (500 mg/m^2) on Day 1 of a 21 day treatment cycle.

Eribulin Mesilate

E7389

Infusion

Intravenous use

Subjects received eribulin mesylate 0.7 mg/m^2, IV infusion in combination with pemetrexed (500 mg/m^2) on Days 1 and 8 of a 21 day treatment cycle.

Eribulin Mesilate

E7389

Infusion

Intravenous use

Subjects received eribulin mesylate 0.9 mg/m^2, IV infusion in combination with pemetrexed (500 mg/m^2) on Day 1 of a 21 day treatment cycle.

Pemetrexed

Infusion

Intravenous use

Subjects received pemetrexed 500 mg/m^2 IV infusion on Day 1 of a 21 day treatment cycle.

Phase 1b: Arm 1 - Cohort 1 (Eribulin+Pemetrexed)

Phase 1b: Arm 1 - Cohort 2 (Eribulin + Pemetrexed)

Phase 1b: Arm 2 - Cohort 1 (Eribulin + Pemetrexed)

Phase 2: Arm 1 (Eribulin 0.9 mg/m^2 + pemetrexed 500 mg/m^2)

Phase 2: Arm 2 (Pemetrexed 500 mg/m^2)

Phase 1b: Arm 1 - Cohort 1 (Eribulin+Pemetrexed)

Phase 1b: Arm 1 - Cohort 2 (Eribulin + Pemetrexed)

Phase 1b: Arm 2 - Cohort 1 (Eribulin + Pemetrexed)

Phase 2: Arm 1 (Eribulin 0.9 mg/m^2 + pemetrexed 500 mg/m^2)

Phase 2: Arm 2 (Pemetrexed 500 mg/m^2)

DLT were defined as clinically significant adverse events (AE) occurring less than or equal to(<=)21 days after treatment.Events as: Non-hematological: 1)Grade greater than or equal to(>=)3 peripheral neuropathy; 2)Grade >=3 nausea,vomiting despite optimal antiemetic treatment; 3)Any nonhematologic toxicity of Grade >=3, with exceptions as alopecia,single laboratory values out of normal range,hypersensitivity reaction. Hematological:1)Grade 4 neutropenia lasting >7 days; 2)Febrile neutropenia as fever >=38.5 degree celsius with absolute neutrophil count less than(<)1.0*10^9 per liter(/L); 3)Grade 3 thrombocytopenia with nontraumatic bleeding requiring platelet transfusion; 4)Grade 4 thrombocytopenia with/without nontraumatic bleeding. Other 1)Study drug related death; 2)Toxicity that dose escalation committee believed to be DLT that was not covered by above DLT criteria. Phase 1b safety analysis set was defined as all subjects enrolled into the Phase 1b portion of this study.

Primary

Cycle 1 (each cycle length = 21 days)

Safety assessment included monitoring and recording all AE including all Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grades (for both increasing and decreasing severity), and serious adverse events (SAE); regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); and performance of physical examinations. A TEAE was defined as an AE that had on onset date, or a worsening in severity from Baseline (pretreatment), on or after the first dose of study drug up to the end of the study. Phase 1b safety analysis set was defined as all subjects enrolled into the Phase 1b portion of this study. As per CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE.

Primary

From date of first dose up to 30 days after the last dose of study drug, up to approximately 1 year 2 months

Safety assessments consisted of monitoring and recording all AEs, including CTCAE version 4.0 grades (for both increasing and decreasing severity), and SAEs, regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and ECGs, and performance of physical examinations. Phase 2 safety population included all subjects enrolled and randomized to treatment in the Phase 2 portion of the study, except for those who (I) dropped out prior to receiving any study drug, (ii) were without any safety assessment following the first dose of study drug.

Primary

From date of first dose up to 30 days after the last dose of study drug, up to approximately 3 years 6 months

PFS was defined as the time from the date of randomization until the earlier of the following two events: the date of PD or the date of death based on response evaluation criteria in solid tumor (RECIST) version 1.1. Progressive disease (PD) is defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan Meier method. Modified intent-to-treat population included all randomized subjects who received at least one dose of study drug without major protocol eligibility violations.

Secondary

From the date of randomization until the earlier of the following two events: the date of PD or the date of death (Up to approximately 3 years 5 months)

From date of first dose up to 30 days after the last dose of study drug (up to approximately 3 years 6 months)

15.0

Phase 1b: Arm 1 - Cohort 1 (Eribulin + Pemetrexed)

Phase 1b: Arm 1 - Cohort 2 (Eribulin + Pemetrexed )

Phase 1b: Arm 2 - Cohort 1 (Eribulin + Pemetrexed)

Phase 2: Arm 1 (Eribulin 0.9 mg/m^2 + pemetrexed 500 mg/m^2)

Phase 2: Arm 2 (Pemetrexed 500 mg/m^2)