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 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.

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
  • Koto-Ku, Japan
    • Eisai Trial Site #12
  • Aichi
    • Nagoya, Aichi, Japan
      • Eisai Trial Site #13
  • Chiba
    • Kashiwa, Chiba, Japan
      • Eisai Trial Site #2
    • Kashiwa City, Chiba, Japan
      • Eisai Trial Site #18
  • Ehime
    • Matsuya, Ehime, Japan
      • Eisai Trial Site #14
  • Fukuoka
    • Kurume, Fukuoka, Japan
      • Eisai Trial Site #4
  • Hyogo
    • Akashi, Hyogo, 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 City, 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: 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
3. 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
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. Participants with any 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

4

Arms and Interventions

Participant Group / 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

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 1b: RP2D of E7389-LF in Combination With Nivolumab		Up to 12 Months
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.	Up to approximately 53 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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 53 Months)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2019
• Primary Completion (Anticipated): January 31, 2024
• Study Completion (Anticipated): January 31, 2024

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): April 27, 2023
• Last Update Submitted That Met QC Criteria: April 26, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Nivolumab; Neoplasms; Solid Tumor; E7389 liposomal formulation
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; 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