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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Neoplasms
• Intervention / Treatment: Drug: E7389-LF; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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)
2. Phase 2 part only: Participants with a confirmed diagnosis of nonresectable gastric cancer (GC), esophageal cancer (EGC) or small cell lung cancer (SCLC) who showed disease progression based on investigator's assessment during or after first line chemotherapy (second-line chemotherapy for GC) and did not receive any other systemic chemotherapy to advanced/recurrent disease
3. Participants who meet the following criteria for biopsy; Phase 1b part: Participants who have accessible tumors for biopsy and agree to 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 to submission of archival tumor tissue, then these participants are eligible regardless of accessible tumors, and consent to biopsy is not necessary
4. Life expectancy of greater than or equal to (>=) 12 weeks
5. Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) 0-1
6. 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:

1. Diagnosed with meningeal carcinomatosis
2. Participants with brain or subdural metastases or invasion are not eligible
3. Active, known, or suspected autoimmune disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 1b, Cohort 1: E7389-LF Dose 1 + Nivolumab Dose 1; Participants will receive E7389-LF (intravenous) Dose 1 and nivolumab (intravenous) Dose 1 on specified days.	Drug: E7389-LF; E7389-LF Intravenous infusion.; Drug: Nivolumab; Nivolumab Intravenous infusion.; Other Names: ONO-4538
Experimental: Phase 1b, Cohort 2: E7389-LF Dose 2 + Nivolumab Dose 1; Participants will receive E7389-LF (intravenous) Dose 2 and nivolumab (intravenous) Dose 1 on specified days.	Drug: E7389-LF; E7389-LF Intravenous infusion.; Drug: Nivolumab; Nivolumab Intravenous infusion.; Other Names: ONO-4538
Experimental: Phase 1b, Cohort 3: E7389-LF Dose 3 + Nivolumab Dose 2; Participants will receive E7389-LF (intravenous) Dose 3 and nivolumab (intravenous) Dose 2 on specified days.	Drug: E7389-LF; E7389-LF Intravenous infusion.; Drug: Nivolumab; Nivolumab Intravenous infusion.; Other Names: ONO-4538
Experimental: Phase 1b, Cohort 4: E7389-LF Dose 4 + Nivolumab Dose 2; Participants will receive E7389-LF (intravenous) Dose 4 and nivolumab (intravenous) Dose 2 on specified days.	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 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b: Number of Participants with Dose Limiting Toxicities (DLTs)	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).	Baseline up to Cycle 1 (Cycle length is equal to [=] up to 28 days)
Phase 2: ORR	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.	Baseline up to End of Treatment (Up to approximately 79 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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 79 months)
Phase 1b and Phase 2: Number of Participants With Markedly Abnormal Laboratory Evaluations		Baseline up to End of Treatment (Up to approximately 79 months)
Phase 1b and Phase 2: Number of Participants With Markedly Abnormal Vital Signs		Baseline up to End of Treatment (Up to approximately 79 months)
Phase 1b and Phase 2: Number of Participants With Clinically Abnormal 12-lead Electrocardiogram (ECG)		Baseline up to End of Treatment (Up to approximately 79 months)
Phase 1b and Phase 2: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)		Baseline up to End of Treatment (Up to approximately 79 months)
Phase 1b and 2: Number of Participants With Clinically Significant Abnormal Physical Examination Findings		Baseline up to End of Treatment (Up to approximately 79 months)
Phase 2: Progression-Free Survival (PFS)	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.	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 79 months)

Collaborators and Investigators

• Sponsor: Eisai Co., Ltd.
• Collaborators: Ono Pharmaceutical Co. Ltd

Publications and helpful links

General Publications

• Oshima T, Yamamoto S, Kawakami H, Makino T, Kawazoe A, Masuishi T, Tsushima T, Hirao M, Tsuda M, Hino K, Yamamoto N, Hara H, Kaname S, Matsuoka D, Otake Y, Yasuda K, Takase T, Takashima S, Semba T, Ooki A. Phase 1b/2 study of the liposomal formulation of eribulin (E7389-LF) in combination with nivolumab: Results from the phase 2 esophageal cancer cohort. BJC Rep. 2024 Sep 4;2(1):66. doi: 10.1038/s44276-024-00066-6.
• Kawazoe A, Yamamoto N, Sugimoto N, Kawakami H, Oshima T, Yamaguchi K, Hino K, Hirao M, Kurokawa Y, Kawakami T, Tsuda M, Hara H, Kaname S, Matsuoka D, Otake Y, Yasuda K, Takase T, Takashima S, Semba T, Muro K. Phase II Study of the Liposomal Formulation of Eribulin (E7389-LF) in Combination with Nivolumab: Results from the Gastric Cancer Cohort. Clin Cancer Res. 2024 Apr 1;30(7):1264-1272. doi: 10.1158/1078-0432.CCR-23-1768.

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2019
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: September 2, 2019
• First Submitted That Met QC Criteria: September 2, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Nivolumab; Neoplasms; Solid Tumor; E7389 liposomal formulation
• Additional Relevant MeSH Terms: Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab
• Other Study ID Numbers: E7389-J081-120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No