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

Study Overview
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Brief Summary
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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.

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

Conditions
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Solid Neoplasms

Intervention / Treatment
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* Drug: E7389-LF
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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E7389 liposomal formulation, Nivolumab, Neoplasms, Solid Tumor