Solid Neoplasms
Conditions
Keywords
E7389 liposomal formulation, Nivolumab, Neoplasms, Solid Tumor
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.
Interventions
DRUGE7389-LF
E7389-LF Intravenous infusion.
DRUGNivolumab
Nivolumab Intravenous infusion.
Sponsors
Eisai Co., Ltd.
Ono Pharmaceutical Co. Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 79 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 79 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. |
Countries
Japan
Outcome results
None listed