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 Dose-limiting Toxicities (DLTs) Cycle 1 (Cycle length=21 days) DLT was graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 based on investigator assessment. DLT was defined as any of the hematological or non-hematological toxicities events that: - Failure to administer greater than or equal to (\>=) 75 percentage (%) of the planned dosage of E7386 as a result of treatment-related toxicity; - Any treatment-related toxicity that causes the participant to discontinue treatment, even if the toxicity does not meet DLT criteria; - Prolonged delay (greater than \[\>\] 2 weeks) in initiating Cycle 2 due to treatment-related toxicities; - Any Grade 5 event or any death not clearly due to the underlying disease or extraneous causes.
Phase 1b Part: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Up to 30 days after last dose of study drug (up to 12.73 months) A TEAE was defined as an adverse event (AE) that emerged during treatment, having been absent at pretreatment (Baseline) or reemerged during treatment, or up to 30 days following last dose of study drug, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment or up to 30 days following last dose of study drug, relative to the pretreatment state, when the AE was continuous.
Phase 1b Part: Number of Participants With Serious TEAEs Up to 90 days after last dose of study drug (up to 14.73 months) An SAE was any untoward medical occurrence that at any dose: Resulted in death; Was life-threatening (i.e., the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death); Required inpatient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity; Was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). An SAE was also counted as a TEAE if it emerged up to 90 days after the participant's last dose of study drug, or up to 30 days following cessation of study drug if the participant initiated new anticancer therapy, whichever was earlier.
Phase 2 Part: Objective Response Rate (ORR) Up to 20.40 months ORR was defined as the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal (i.e., decrease in short axis to less than \[\<\] 10 millimeters \[mm\]). PR: At least a 30 percent (%) decrease in sum of the diameters (SOD) of target lesions, taking as reference the screening SOD. Additionally, progression of target lesions must not be present.
- Secondary Outcome Measures
Name Time Method Phase 1b Part: Percentage of Participants With Best Overall Response (BOR) Up to 11.73 months BOR was defined as CR, PR, stable disease (SD), progressive disease (PD), and not applicable (NA)/not evaluable (NE) as per RECIST version 1.1. CR: Disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal (i.e., decrease in short axis to \<10 mm). PR: At least a 30% decrease in SOD of target lesions, taking as reference screening SOD. Additionally, progression of target lesions must not be present. SD: Neither sufficient shrinkage of target lesions to qualify for PR, nor sufficient increase to qualify for PD. PD: At least a 20% increase in the SOD of target lesions, taking as reference nadir SOD (or the screening, if screening is nadir value). In addition to relative increase of 20% in SOD, the SOD must also demonstrate an absolute increase of \>=5 mm. NA: No target lesions were identified at Screening.
Phase 1b and Phase 2 Parts: Duration of Response (DOR) Phase 1b Part: Up to 11.73 months; Phase 2 Part: Up to 20.40 months DOR was defined as the time from the first documentation of CR or PR to the first documentation of PD or death due to any cause (whichever occurs first), in participants with confirmed CR or PR per RECIST 1.1. CR: Disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal (i.e., decrease in short axis to \<10 mm). PR: At least a 30% decrease in SOD of target lesions, taking as reference screening SOD. Additionally, progression of target lesions must not be present. SD: Neither sufficient shrinkage of target lesions to qualify for PR, nor sufficient increase to qualify for PD. PD: At least a 20% increase in the SOD of target lesions, taking as reference nadir SOD (or the screening, if screening is nadir value). In addition to relative increase of 20% in SOD, the SOD must also demonstrate an absolute increase of \>=5 mm.
Phase 1b and Phase 2 Parts: Disease Control Rate (DCR) Phase 1b Part: Up to 11.73 months; Phase 2 Part: Up to 20.40 months DCR was defined as the percentage of participants who had a best overall response of confirmed CR or PR, or SD (after \>=5 weeks from the first dose) as per RECIST 1.1. CR: Disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal (i.e., decrease in short axis to \<10 mm). PR: At least a 30% decrease in SOD of target lesions, taking as reference screening SOD. Additionally, progression of target lesions must not be present. SD: Neither sufficient shrinkage of target lesions to qualify for PR, nor sufficient increase to qualify for PD. PD: At least a 20% increase in the SOD of target lesions, taking as reference nadir SOD (or the screening, if screening is nadir value). In addition to relative increase of 20% in SOD, the SOD must also demonstrate an absolute increase of \>=5 mm.
Phase 1b and Phase 2 Parts: Clinical Benefit Rate (CBR) Phase 1b Part: Up to 11.73 months; Phase 2 Part: Up to 20.40 months CBR was defined as the percentage of participants who had a best overall response of confirmed CR or PR, or durable SD (duration of SD \>=23 weeks) per RECIST 1.1. CR: Disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal (i.e., decrease in short axis to \<10 mm). PR: At least a 30% decrease in SOD of target lesions, taking as reference screening SOD. Additionally, progression of target lesions must not be present. SD: Neither sufficient shrinkage of target lesions to qualify for PR, nor sufficient increase to qualify for PD.
Phase 2 Part: Number of Participants With TEAEs and Treatment-related TEAEs Up to 30 days after last dose of study drug (up to 21.40 months) A TEAE was defined as an AE that emerged during treatment, having been absent at pretreatment (Baseline) or reemerged during treatment, or up to 30 days following last dose of study drug, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment or up to 30 days following last dose of study drug, relative to the pretreatment state, when the AE was continuous. Related TEAEs was defined as AE for which a causal relationship between the study drug and the AE was a reasonable possibility.
Phase 1b Part, Cmax: Maximum Observed Plasma Concentration for E7386 When Co-administered With Pembrolizumab Cycle 1 Days 1 and 8: Pre-dose up to 12 hours post-dose (Cycle 1 length=21 days) Cmax was defined as the maximum plasma concentration for E7386 when co-administered with Pembrolizumab. PK parameters were derived by noncompartmental analysis.
Phase 1b Part, Tmax: Time to Reach the Maximum Plasma Concentration for E7386 When Co-administered With Pembrolizumab Cycle 1 Days 1 and 8: Pre-dose up to 12 hours post-dose (Cycle 1 length=21 days) Tmax was defined as the time to reach maximum observed plasma concentration for E7386 when co-administered with Pembrolizumab. PK parameters were derived by noncompartmental analysis.
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: Pre-dose up to 12 hours post-dose (Cycle 1 length=21 days) AUC(0-t) was defined as the area under the plasma concentration-time curve from 0 (pre-dose) to time of last quantifiable concentration for E7386 when co-administered with Pembrolizumab. PK parameters were derived by noncompartmental analysis.
Phase 1b Part, CLss/F: Apparent Clearance From Plasma at Steady State for E7386 When Co-administered With Pembrolizumab Cycle 1 Day 8: Pre-dose up to 12 hours post-dose (Cycle 1 length=21 days) CLss/F for E7386 when co-administered with Pembrolizumab was reported. PK parameters were derived by noncompartmental analysis.
Trial Locations
- Locations (32)
Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Providence Medical Center Institute Franz Clinic
🇺🇸Portland, Oregon, United States
Tennessee Oncology PPLC
🇺🇸Nashville, Tennessee, United States
Imperial College London - Hammersmith Hospital
🇬🇧London, United Kingdom
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
University of California, Irvine Health
🇺🇸Orange, California, United States
Florida Cancer Specialists
🇺🇸Fort Myers, Florida, United States
SCRI Florida Cancer Specialists East
🇺🇸West Palm Beach, Florida, United States
Barbara Ann Karmanos Cancer Center
🇺🇸Detroit, Michigan, United States
Rutgers cancer Institute of NJ
🇺🇸New Brunswick, New Jersey, United States
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