Clinical trial NCT04078295: A Study of E7389 Liposomal Formulation (E7389-LF) Plus Nivolumab in Participants With Solid Tumor
Official title: An Open-Label Phase 1b/2 Study of E7389 Liposomal Formulation Plus Nivolumab in Subjects With Solid Tumor
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Neoplasms
Keywords: E7389 liposomal formulation
Nivolumab
Neoplasms
Solid Tumor
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2019-09-06
Enrollment: 125
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Phase 1b: Number of Participants with Dose Limiting Toxicities (DLTs)
timeFrame: Baseline up to Cycle 1 (Cycle length is equal to [=] up to 28 days)
measure: Phase 2: ORR
timeFrame: Baseline up to End of Treatment (Up to approximately 65 months)
Secondary outcomes:
measure: Phase 1b and Phase 2: Number of Participants With AEs and Serious Adverse Events (SAEs)
timeFrame: 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)
measure: Phase 1b and Phase 2: Number of Participants With Markedly Abnormal Laboratory Evaluations
timeFrame: Baseline up to End of Treatment (Up to approximately 65 months)
measure: Phase 1b and Phase 2: Number of Participants With Markedly Abnormal Vital Signs
timeFrame: Baseline up to End of Treatment (Up to approximately 65 months)
measure: Phase 1b and Phase 2: Number of Participants With Clinically Abnormal 12-lead Electrocardiogram (ECG)
timeFrame: Baseline up to End of Treatment (Up to approximately 65 months)
measure: Phase 1b and Phase 2: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
timeFrame: Baseline up to End of Treatment (Up to approximately 65 months)
measure: Phase 1b and 2: Number of Participants With Clinically Significant Abnormal Physical Examination Findings
timeFrame: Baseline up to End of Treatment (Up to approximately 65 months)
measure: Phase 1b and Phase 2, Cmax: Maximum Observed Plasma Concentration of E7389-LF
timeFrame: 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)
measure: Phase 1b and Phase 2: Serum Concentration of Nivolumab
timeFrame: Up to Cycle 13 (each Cycle length = up to 28 days)
measure: Phase 1b and Phase 2, Tmax: Time to Maximum Observed Plasma Concentration (Cmax) of E7389-LF
timeFrame: 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)
measure: Phase 1b and Phase 2, AUC: Area Under the Plasma Concentration-time Curve Over Time From 0 to Last Measurable Concentration of E7389-LF
timeFrame: 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)
measure: Phase 1b and Phase 2, T1/2: Terminal Phase Elimination Half-life of E7389-LF
timeFrame: 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)
measure: Phase 1b and Phase 2, CL: Total Body Clearance of E7389-LF
timeFrame: 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)
measure: Phase 1b and Phase 2, Vd: Volume of Distribution of E7389-LF
timeFrame: 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)
measure: Phase 2: Progression-Free Survival (PFS)
timeFrame: 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)
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Eisai Trial Site #13
state: Aichi
city: Kashiwa City
country: Japan
facility: Eisai Trial Site #18
state: Chiba
city: Kashiwa
country: Japan
facility: Eisai Trial Site #2
state: Chiba
city: Matsuya
country: Japan
facility: Eisai Trial Site #14
state: Ehime
city: Kurume
country: Japan
facility: Eisai Trial Site #4
state: Fukuoka
city: Akashi
country: Japan
facility: Eisai Trial Site #11
state: Hyogo
city: Yokohama
country: Japan
facility: Eisai Trial Site #15
state: Kanaga
city: Sendai
country: Japan
facility: Eisai Trial Site #3
state: Miyagi
city: Chuo Ku
country: Japan
facility: Eisai Trial Site #6
state: Osaka
city: Chuo Ku
country: Japan
facility: Eisai Trial Site #8
state: Osaka
city: Osakasa
country: Japan
facility: Eisai Trial Site #5
state: Osaka
city: Sakai C
country: Japan
facility: Eisai Trial Site #7
state: Osaka
city: Suita City
country: Japan
facility: Eisai Trial Site #17
state: Osaka
city: Kitaadachi-gun
country: Japan
facility: Eisai Trial Site #19
state: Saitama
city: Sunto-g
country: Japan
facility: Eisai Trail Site #16
state: Shizuo
city: Chuo Ku
country: Japan
facility: Eisai Trial Site #1
state: Tokyo
city: Koto-Ku
country: Japan
facility: Eisai Trial Site #10
state: Tokyo
city: Wakayama
country: Japan
facility: Eisai Trial Site #9
state: Wakaya
city: Koto-Ku
country: Japan
facility: Eisai Trial Site #12
Study officials:
References: