A Study of E7386 in Combination With Pembrolizumab in Previously Treated Participants With Selected Solid Tumors
- Conditions
- Carcinoma, HepatocellularMelanomaColorectal Neoplasms
- Interventions
- Registration Number
- NCT05091346
- Lead Sponsor
- Eisai Inc.
- Brief Summary
The Phase 1b part of this study is conducted to assess the safety and tolerability of E7386 in combination with pembrolizumab in participants with previously treated selected solid tumors, and to determine the recommended Phase 2 dose (RP2D) of E7386 in combination with pembrolizumab.
The Phase 2 part of this study is conducted to assess the objective response rate (ORR) of E7386 in combination with pembrolizumab (melanoma, colorectal cancer \[CRC\], hepatocellular carcinoma \[HCC\]) or of E7386 in combination with pembrolizumab plus lenvatinib (HCC) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 89
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1b and 2: E7386 + Pembrolizumab E7386 Participants will receive E7386 twice daily (BID) along with pembrolizumab 200 mg intravenous (IV) infusion once every 3 weeks (Q3W) in 21-day treatment cycle until RP2D is determined in Phase 1b. The recommended dose for Phase 2 part of the study will be based on Phase 1b result. Participants will continue to receive study treatment in Phase 2 part until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the study. Phase 2: E7386 + Pembrolizumab + Lenvatinib E7386 Participants will be randomized to receive E7386 Dose 1 (Cohort 1) or Dose 2 (Cohort 2) tablet, BID, orally in combination with pembrolizumab 200 mg Q3W IV infusion plus lenvatinib 8 mg capsule, orally, once daily (QD) continuously in 21-days treatment cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the study. The dose of treatment depends on tolerability data of both Cohorts. Phase 2: E7386 + Pembrolizumab + Lenvatinib Pembrolizumab Participants will be randomized to receive E7386 Dose 1 (Cohort 1) or Dose 2 (Cohort 2) tablet, BID, orally in combination with pembrolizumab 200 mg Q3W IV infusion plus lenvatinib 8 mg capsule, orally, once daily (QD) continuously in 21-days treatment cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the study. The dose of treatment depends on tolerability data of both Cohorts. Phase 1b and 2: E7386 + Pembrolizumab Pembrolizumab Participants will receive E7386 twice daily (BID) along with pembrolizumab 200 mg intravenous (IV) infusion once every 3 weeks (Q3W) in 21-day treatment cycle until RP2D is determined in Phase 1b. The recommended dose for Phase 2 part of the study will be based on Phase 1b result. Participants will continue to receive study treatment in Phase 2 part until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the study. Phase 2: E7386 + Pembrolizumab + Lenvatinib Lenvatinib Participants will be randomized to receive E7386 Dose 1 (Cohort 1) or Dose 2 (Cohort 2) tablet, BID, orally in combination with pembrolizumab 200 mg Q3W IV infusion plus lenvatinib 8 mg capsule, orally, once daily (QD) continuously in 21-days treatment cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the study. The dose of treatment depends on tolerability data of both Cohorts.
- Primary Outcome Measures
Name Time Method Phase 1b Part: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) From date of first dose of study drug up to 30 days after last administration of study drug (approximately up to 3 years 11 months) Phase 2 Part: Objective Response Rate (ORR) From first dose of study drug until progressive disease (PD) or death, development of unacceptable toxicity, withdrawal of consent, or study termination (up to approximately 3 years 11 months) ORR is defined as the percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Phase 1b Part: Number of Participants With Dose-limiting Toxicities (DLTs) Cycle 1 (Cycle length is equal to [=] 21 days) DLTs are any pre-specified toxicities occurring during Cycle 1, based on investigator assessment as related to study drug. All adverse events (AEs) of the specified grades should count as DLTs except those that are clearly and incontrovertibly due to disease progression or extraneous causes. DLTs will be assessed to determine the RP2D of E7386 in combination with pembrolizumab. All toxicity will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) From the date of first documented CR or PR until first documentation of recurrent or progressive disease or death due to any causes (up to approximately 3 years 11 months) DOR is defined as the time from the first documentation of CR or PR to the first documentation of disease progression or death due to any causes, whichever occurs first in participants with confirmed CR or PR as per RECIST version 1.1.
Phase 2 Part: Number of Participants With TEAEs and Treatment-related Adverse Events for E7386 in Combination With Pembrolizumab and E7386 in Combination With Pembrolizumab Plus Lenvatinib From date of first dose of study drug up to 30 days after last administration of study drug (approximately up to 3 years 11 months) Phase 2 Part: Number of Participants With DLTs for E7386 in Combination With Pembrolizumab Plus Lenvatinib Cycle 1 (Cycle length = 21 days) DLTs are any pre-specified toxicities occurring during Cycle 1, based on investigator assessment as related to study drug. All AEs of the specified grades should count as DLTs except those that are clearly and incontrovertibly due to disease progression or extraneous causes. All toxicity will be graded using NCI CTCAE version 5.0.
Phase 1b Part: Best of Response (BOR) From first dose of study drug until PD or death, development of unacceptable toxicity, withdrawal of consent, or study termination (up to approximately 3 years 11 months) BOR is defined as CR, PR, stable disease (SD), PD, and not evaluable (NE), where SD has to be achieved at greater than equal to (\>=) 5 weeks after the first dose per RECIST version 1.1.
Phase 1b Part, Tmax: Time to Reach the Maximum Plasma Concentration for E7386 When Co-administered With Pembrolizumab Cycle 1 Days 1 and 8: 0-12 hours post-dose (Cycle length = 21 days) Phase 1b Part, AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration for E7386 When Co-administered With Pembrolizumab Cycle 1 Days 1 and 8: 0-12 hours post-dose (Cycle length = 21 days) Phase 2 Part: Apparent Clearance for E7386 When Co-administered With Lenvatinib and Pembrolizumab Cycle 1 Day 1: 0.5-8 hours post-dose; Cycle 1 Day 8: 0-8 hours post-dose (Cycle length = 21 days) Phase 2 Part: Apparent Clearance for Lenvatinib When Co-administered With E7386 and Pembrolizumab Cycle 1 Day 1: 0.5-8 hours post-dose; Cycle 1 Day 8: 0-8 hours post-dose (Cycle length = 21 days) Clinical Benefit Rate (CBR) From first dose of study drug until PD or death, development of unacceptable toxicity, withdrawal of consent, or study termination (up to approximately 3 years 11 months) CBR is defined as the percentage of participants who have a BOR of confirmed CR, PR, or durable SD (duration of SD \>=23 weeks) per RECIST 1.1.
Phase 1b Part, Cmax: Maximum Observed Plasma Concentration for E7386 When Co-administered With Pembrolizumab Cycle 1 Days 1 and 8: 0-12 hours post-dose (Cycle length = 21 days) Disease Control Rate (DCR) From first dose of study drug until PD or death, development of unacceptable toxicity, withdrawal of consent, or study termination (up to approximately 3 years 11 months) DCR is defined as the percentage of participants with BOR of confirmed CR, PR, or SD after \>=5 weeks from first dose per RECIST version 1.1.
Trial Locations
- Locations (33)
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Providence Medical Center
🇺🇸Portland, Oregon, United States
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario de la Paz
🇪🇸Madrid, Spain
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
The Royal Marsden NHS Foundation Trust - The Royal Marsden Hospital
🇬🇧Sutton, Surrey, United Kingdom
Imperial College London
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Consorcio Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
ClĂnica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
University of California, Irvine Health
🇺🇸Orange, California, United States
Chiba University Hospital
🇯🇵Chiba-shi, Japan
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Osaka Metropolitan University Hospital
🇯🇵Osaka, Japan
Shizuoka Cancer Center Hospital
🇯🇵Shizouka, Japan
Toranomon Hospital
🇯🇵Tokyo, Japan
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Avenida Carolos Haya S/n, Spain
Hospital ClĂnico San Carlos
🇪🇸Madrid, Calle Profesor MartĂn Lagos, Spain
Hospital Universitario de Badajoz
🇪🇸Badajoz, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Royal Free Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
National Cancer Center Hospital
🇯🇵Chuo-ku, Japan
Sapporo-Kosei General Hospital
🇯🇵Sapporo shi, Japan
SCRI Florida Cancer Specialists East
🇺🇸West Palm Beach, Florida, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Sarah Cannon Cancer Care in Nashville
🇺🇸Nashville, Tennessee, United States
Kurume University Hospital
🇯🇵Fukuoka, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Rutgers cancer Institute of NJ
🇺🇸New Brunswick, New Jersey, United States
Florida Cancer Specialists
🇺🇸Fort Myers, Florida, United States
Barbara Ann Karmanos Cancer Center
🇺🇸Detroit, Michigan, United States