A Study of E7389 Liposomal Formulation (E7389-LF) Plus Nivolumab in Participants With Solid Tumor

Sponsor

Eisai Co., Ltd. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04078295

Collaborator

Ono Pharmaceutical Co. Ltd (Industry)

125

Enrollment

Locations

Arms

52.9

Anticipated Duration (Months)

6.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary purpose of the study is to evaluate safety and tolerability and to determine recommended Phase 2 dose (RP2D) of E7389-LF in combination with nivolumab in Phase 1b part, and to evaluate objective response rate (ORR) of E7389-LF and nivolumab using RP2D in Phase 2 part in each tumor type.

Condition or Disease	Intervention/Treatment	Phase
Solid Neoplasms	Drug: E7389-LF Drug: Nivolumab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

125 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-Label Phase 1b/2 Study of E7389 Liposomal Formulation Plus Nivolumab in Subjects With Solid Tumor

Actual Study Start Date :

Sep 5, 2019

Actual Primary Completion Date :

May 31, 2022

Anticipated Study Completion Date :

Jan 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1b: E7389-LF + Nivolumab Participants will receive specified doses of E7389-LF (intravenous) and nivolumab (intravenous) on specified days.	Drug: E7389-LF E7389-LF Intravenous infusion. Drug: Nivolumab Nivolumab Intravenous infusion. Other Names: ONO-4538
Experimental: Phase 2, Cohort-1: E7389-LF + Nivolumab Participants with gastric cancer will receive RP2D of E7389-LF (intravenous) and nivolumab (intravenous) determined in Phase 1b part.	Drug: E7389-LF E7389-LF Intravenous infusion. Drug: Nivolumab Nivolumab Intravenous infusion. Other Names: ONO-4538
Experimental: Phase 2, Cohort-2: E7389-LF + Nivolumab Participants with esophageal cancer will receive RP2D of E7389-LF (intravenous) and nivolumab (intravenous) determined in Phase 1b part.	Drug: E7389-LF E7389-LF Intravenous infusion. Drug: Nivolumab Nivolumab Intravenous infusion. Other Names: ONO-4538
Experimental: Phase 2, Cohort-3: E7389-LF + Nivolumab Participants with small cell lung cancer will receive RP2D of E7389-LF (intravenous) and nivolumab (intravenous) determined in Phase 1b part.	Drug: E7389-LF E7389-LF Intravenous infusion. Drug: Nivolumab Nivolumab Intravenous infusion. Other Names: ONO-4538

Outcome Measures

Primary Outcome Measures

Phase 1b: Number of Participants with Dose Limiting Toxicities (DLTs) [Baseline up to Cycle 1 (Cycle length is equal to [=] up to 28 days)]
DLTs are defined as study drug related adverse events (AEs). Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0).
Phase 1b: RP2D of E7389-LF in Combination With Nivolumab [Up to 12 Months]
Phase 2: ORR [Up to approximately 53 Months]
ORR is defined as the percentage of participants who have best overall response of complete response (CR) or partial response (PR). The ORR will be assessed by investigator based on response evaluation criteria in solid tumors (RECIST) version 1.1.

Secondary Outcome Measures

Phase 1b and Phase 2: Number of Participants With AEs and Serious Adverse Events (SAEs) [Up to 30 days after the last dose of study drug or before initiating post anti-cancer treatment, whichever shorter (up to approximately 53 Months)]
Phase 1b and Phase 2, Cmax: Maximum Observed Plasma Concentration of E7389-LF [Phase 1b, Cycle 1 Day 1: 0 to 24 hours, Cycle 1 Days 4 and 8; Phase 2, Cycle 1 Days 1 and 8 (Cycle length = up to 28 days)]
Phase 1b and Phase 2: Serum Concentration of Nivolumab [Up to Cycle 13 (each Cycle length = up to 28 days)]
Phase 1b and Phase 2, Tmax: Time to Maximum Observed Plasma Concentration (Cmax) of E7389-LF [Phase 1b, Cycle 1 Day 1: 0 to 24 hours, Cycle 1 Days 4 and 8; Phase 2, Cycle 1 Days 1 and 8 (Cycle length = up to 28 days)]
Phase 1b and Phase 2, AUC: Area Under the Plasma Concentration-time Curve Over Time From 0 to Last Measurable Concentration of E7389-LF [Phase 1b, Cycle 1 Day 1: 0 to 24 hours, Cycle 1 Days 4 and 8; Phase 2, Cycle 1 Days 1 and 8 (Cycle length = up to 28 days)]
Phase 1b and Phase 2, T1/2: Terminal Phase Elimination Half-life of E7389-LF [Phase 1b, Cycle 1 Day 1: 0 to 24 hours, Cycle 1 Days 4 and 8; Phase 2, Cycle 1 Days 1 and 8 (Cycle length = up to 28 days)]
Phase 1b and Phase 2, CL: Total Body Clearance of E7389-LF [Phase 1b, Cycle 1 Day 1: 0 to 24 hours, Cycle 1 Days 4 and 8; Phase 2, Cycle 1 Days 1 and 8 (Cycle length = up to 28 days)]
Phase 1b and Phase 2, Vd: Volume of Distribution of E7389-LF [Phase 1b, Cycle 1 Day 1: 0 to 24 hours, Cycle 1 Days 4 and 8; Phase 2, Cycle 1 Days 1 and 8 (Cycle length = up to 28 days)]
Phase 2: Progression-Free Survival (PFS) [From the first does of the study drug up to the first documentation of disease progression or death due to any cause, whichever comes first (up to approximately 53 Months)]
PFS is defined as the time from the date of the first administration of drug to the date of the first documentation of disease progression or death due to any cause, whichever comes first. The PFS will be assessed by investigator based on RECIST version 1.1.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Phase 1b part only: Participants with advanced, nonresectable, or recurrent solid tumor for which no alternative standard therapy or no effective therapy exists (participants who will be the candidate of treatment by nivolumab monotherapy as standard therapy is acceptable)
Phase 2 part only: Nonresectable specific solid tumor participants with confirmed diagnosis who showed disease progression by investigator's assessment during or after 1st line chemotherapy and did not receive any other systemic chemotherapy to advanced/recurrent disease
Participants who meet the following biopsy criteria; Phase 1b part: Participants who have accessible tumors for biopsy and agree with tumor biopsy for pre and post treatment of study drug (If a pre-treatment biopsy cannot be obtained due to safety issue, then an archival tumor tissue sample may be submitted.) Phase 2 part: Participants who have accessible tumors for biopsy and agree with tumor biopsy for pre and post treatment of study drug (As an alternative to pre-treatment biopsy, tumor tissue sample taken from recurrent or advanced disease may be submitted). However, if the sponsor and the investigator discuss and agree in advance, and the participants agree with submission of archival tumor tissue, then these participants are eligible regardless of accessible tumors, and consent to biopsy is not necessary
Life expectancy of greater than or equal to (>=) 12 weeks
Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) 0-1
Phase 2 part only: At least one measurable lesion based on RECIST 1.1 (Lesions that have had radiotherapy or loco-regional therapies must show evidence of progressive disease to be deemed a measurable lesion)

Exclusion Criteria:

Diagnosed with meningeal carcinomatosis
Participants with brain or subdural metastases or invasion are not eligible
Participants with any active, known, or suspected autoimmune disease

Contacts and Locations

Locations

	Site	City	State	Country
1	Eisai Trial Site #13	Nagoya	Aichi	Japan
2	Eisai Trial Site #18	Kashiwa City	Chiba	Japan
3	Eisai Trial Site #2	Kashiwa	Chiba	Japan
4	Eisai Trial Site #14	Matsuya	Ehime	Japan
5	Eisai Trial Site #4	Kurume	Fukuoka	Japan
6	Eisai Trial Site #11	Akashi	Hyogo	Japan
7	Eisai Trial Site #15	Yokohama	Kanaga	Japan
8	Eisai Trial Site #3	Sendai	Miyagi	Japan
9	Eisai Trial Site #6	Chuo Ku	Osaka	Japan
10	Eisai Trial Site #8	Chuo Ku	Osaka	Japan
11	Eisai Trial Site #5	Osakasa	Osaka	Japan
12	Eisai Trial Site #7	Sakai C	Osaka	Japan
13	Eisai Trial Site #17	Suita City	Osaka	Japan
14	Eisai Trial Site #19	Kitaadachi-gun	Saitama	Japan
15	Eisai Trail Site #16	Sunto-g	Shizuo	Japan
16	Eisai Trial Site #1	Chuo Ku	Tokyo	Japan
17	Eisai Trial Site #10	Koto-Ku	Tokyo	Japan
18	Eisai Trial Site #9	Wakayama	Wakaya	Japan
19	Eisai Trial Site #12	Koto-Ku		Japan