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

Phase 1

Active, not recruiting

• Conditions: Solid Neoplasms
• Interventions: Drug: E7389-LF; Drug: Nivolumab

• Registration Number: NCT04078295
• Lead Sponsor: Eisai Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-09-02
• Study First Submitted QC: 2019-09-02
• Study Start: 2019-09-05
• Study First Posted: 2019-09-06
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-10
• Primary Completion: 2026-03-31
• Study Completion: 2026-03-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 125

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1b: E7389-LF + Nivolumab	Nivolumab	Participants will receive specified doses of E7389-LF (intravenous) and nivolumab (intravenous) on specified days.
Phase 2, Cohort-1: E7389-LF + Nivolumab	E7389-LF	Participants with gastric cancer will receive RP2D of E7389-LF (intravenous) and nivolumab (intravenous) determined in Phase 1b part.
Phase 2, Cohort-1: E7389-LF + Nivolumab	Nivolumab	Participants with gastric cancer will receive RP2D of E7389-LF (intravenous) and nivolumab (intravenous) determined in Phase 1b part.
Phase 2, Cohort-2: E7389-LF + Nivolumab	E7389-LF	Participants with esophageal cancer will receive RP2D of E7389-LF (intravenous) and nivolumab (intravenous) determined in Phase 1b part.
Phase 1b: E7389-LF + Nivolumab	E7389-LF	Participants will receive specified doses of E7389-LF (intravenous) and nivolumab (intravenous) on specified days.
Phase 2, Cohort-2: E7389-LF + Nivolumab	Nivolumab	Participants with esophageal cancer will receive RP2D of E7389-LF (intravenous) and nivolumab (intravenous) determined in Phase 1b part.
Phase 2, Cohort-3: E7389-LF + Nivolumab	E7389-LF	Participants with small cell lung cancer will receive RP2D of E7389-LF (intravenous) and nivolumab (intravenous) determined in Phase 1b part.
Phase 2, Cohort-3: E7389-LF + Nivolumab	Nivolumab	Participants with small cell lung cancer will receive RP2D of E7389-LF (intravenous) and nivolumab (intravenous) determined in Phase 1b part.

Primary Outcome Measures

Name	Time	Method
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 2: ORR	Baseline up to End of Treatment (Up to approximately 65 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

Name	Time	Method
Phase 1b and 2: Number of Participants With Clinically Significant Abnormal Physical Examination Findings	Baseline up to End of Treatment (Up to approximately 65 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: 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 65 months)
Phase 1b and Phase 2: Number of Participants With Markedly Abnormal Laboratory Evaluations	Baseline up to End of Treatment (Up to approximately 65 months)
Phase 1b and Phase 2: Number of Participants With Markedly Abnormal Vital Signs	Baseline up to End of Treatment (Up to approximately 65 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 65 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 65 months)
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 65 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.

Trial Locations

Locations (19)

Eisai Trial Site #11; 🇯🇵 Akashi, Hyogo, Japan

Eisai Trial Site #18; 🇯🇵 Kashiwa City, Chiba, Japan

Eisai Trial Site #2; 🇯🇵 Kashiwa, Chiba, Japan

Eisai Trial Site #14; 🇯🇵 Matsuya, Ehime, Japan

Eisai Trial Site #6; 🇯🇵 Chuo Ku, Osaka, Japan

Eisai Trial Site #13; 🇯🇵 Nagoya, Aichi, Japan

Eisai Trial Site #4; 🇯🇵 Kurume, Fukuoka, Japan

Eisai Trial Site #15; 🇯🇵 Yokohama, Kanaga, Japan

Eisai Trial Site #3; 🇯🇵 Sendai, Miyagi, Japan

Eisai Trial Site #8; 🇯🇵 Chuo Ku, Osaka, Japan

Eisai Trial Site #5; 🇯🇵 Osakasa, Osaka, Japan

Eisai Trial Site #7; 🇯🇵 Sakai C, Osaka, Japan

Eisai Trial Site #17; 🇯🇵 Suita City, Osaka, Japan

Eisai Trial Site #19; 🇯🇵 Kitaadachi-gun, Saitama, Japan

Eisai Trail Site #16; 🇯🇵 Sunto-g, Shizuo, Japan

Eisai Trial Site #1; 🇯🇵 Chuo Ku, Tokyo, Japan

Eisai Trial Site #9; 🇯🇵 Wakayama, Wakaya, Japan

Eisai Trial Site #10; 🇯🇵 Koto-Ku, Tokyo, Japan

Eisai Trial Site #12; 🇯🇵 Koto-Ku, Japan