Advanced Solid Tumors
Conditions
Brief summary
This study consists of two Parts. Part A (Food Effect Study) and Part B (Determination of Maximum Tolerated Dose \[MTD\] for twice daily \[BID\] Dosing).Part A will be initiated first, and Part B will be initiated after the PK results of Part A have been evaluated.
Interventions
DRUGE7820
FOOD EFFECT STUDY: Each subject (a minimum of 12 subjects) will be assigned according to a randomization code to receive a single 50 mg dose of E7820 on Day 1, either after fasting for 10 hours, or immediately after consuming a high fat breakfast. Following a 7-day washout period, the subjects will crossover and a second 50 mg dose of E7820 will be administered on Day 8.
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or older. 2. Histological or cytological evidence of an unresectable or refractory solid tumor. 3. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 4. Subjects with known brain metastases will be eligible under the following conditions A. Have undergone complete surgical excision and are more then 1 month post surgery with no radiographic evidence of brain disease recurrence or B. Have undergone stereotactic radio surgery (gamma knife procedure) and are more then 1 month post procedure and with no radiographic evidence of brain disease progression and C. Are asymptomatic and D. Discontinued corticosteroid treatment at least 30 days prior to Cycle 1, Day 1 5. Adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the upper limits of normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 x ULN (in the case of liver metastases less than or equal to 5 x ULN) In case alkaline phosphatase is greater than 3 x ULN (in absence of liver metastases) or greater than 5 x ULN (in presence of liver metastases) AND subject also is known to have bone metastases, the liver specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase. 6. Adequate renal function as evidenced by serum creatinine less than or equal to 2.0 mg/dL (177 micro-mol/L) or calculated creatinine clearance greater than or equal to 40 mL/min per the Cockcroft and Gault formula 7. Provide written informed consent. 8. Are willing and able to comply with all aspects of the protocol. 9. Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L, hemoglobin greater than or equal to 9 g/dL (5.5 mmol/L) and platelet count greater than or equal to 100 x 109/L. 10. Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin \[beta-hCG\] test with a minimum sensitivity of 25 IU/L or equivalent units of beta-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug. 11. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). 12. Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double-barrier method \[such as condom plus diaphragm with spermicide\], a contraceptive implant, an oral contraceptive or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the subject must agree to use a double-barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation. 13. Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation). No sperm donation is allowed during the study period and for 30 days after study drug discontinuation.
Exclusion criteria
1. Leptomeningeal metastases or brain metastases (except as for inclusion criteria #4). 2. Active hemoptysis (at least 2.5 mL \[0.5 teaspoon\] bright red blood) within 3 weeks prior to the first dose of study drug. 3. Hypersensitivity to sulfonamide derivatives. 4. Subjects who have had radiation to greater than or equal to 30% of their bone marrow. 5. Subjects who require therapeutic anti-coagulant therapy with warfarin or related vitamin K antagonists. Prophylactic doses of heparin or low molecular weight heparin or thrombin inhibitors may be used in place of warfarin. 6. Left ventricular ejection fraction less than 50% on echocardiography or MUGA scanning. 7. Anticancer therapies that have not been completed at least 28 days (42 days in the case of mitomycin C or nitrosoureas) prior to treatment with E7820 (other than surgery or treatment with a protein kinase inhibitor which must have been completed no less than one week prior to treatment with E7820). 8. Incomplete recovery from previous radiotherapy, chemotherapy, or surgery other than residual cutaneous effects or stable less than Grade 2 gastrointestinal toxicity. 9. History of an ischemic cardiac event, myocardial infarction or unstable cardiac disease within 3 months before study entry. 10. A clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolongation of QTc interval greater than 480 msec. 11. Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the subject's safety or study conduct. 12. Concurrent treatment with CYP3A4 inhibitors such as verapamil, cyclosporin, quinidine, erythromycin, mibefradil, clarithramycin and azoles. 13. Concurrent treatment with drugs known to be extensively metabolized by CYP2C9 and/or CYP2C19. 14. Chronic treatment with known inducers of CYP3A4 within four weeks of receiving treatment with E7820 other than corticosteroids (Appendix 6). 15. Subjects who have a positive test result for human immunodeficiency virus (HIV), hepatitis A, hepatitis B or hepatitis C. 16. Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics or prior suicide attempt(s) within approximately the last 2 years. 17. History of drug or alcohol dependency or abuse within approximately the last 2 years. 18. Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors. 19. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen. 20. Use of illegal recreational drugs. 21. Any medical or other condition that, in the opinion of the investigator, would preclude the subject's participation in a study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Phase Part B: Maximum Tolerated Dose (MTD) of E7820 BID Dosing Schedule | Up to Cycle 6 (Cycle length =28 days) | MTD defined as the highest dose level at which no more than 1 of 6 participants experienced a dose-limiting toxicity(DLT), with the next higher dose having at least 2 of 3 or 2 of 6 participants experiencing DLTs. DLTs were defined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events(CTCAE) Version 4.03 as: Neutropenia less than(\<) 0.5\*10\^9/liter(L) for greater than(\>) 5 days; neutropenia \<1\*10\^9/L with fever; thrombocytopenia \<25\*10\^9/L accompanied by bleeding or thrombocytopenia \<10\*10\^9/L; any Grade 3 or 4 nonhematological toxicity for which the study drug could not be excluded as a cause (other than nausea, vomiting or diarrhea in the absence of appropriate prophylaxis) with the following clarification: Grade 3 or 4 nonhematological laboratory abnormalities for which there was no expected clinical correlation would not be considered DLTs; treatment delay of \>14 days required to recover from E7820-related toxicities. |
| Treatment Phase Part A: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for E7820 | Day 1 or 8: 0.5-48 hours | — |
| Treatment Phase Part A: AUC(0-t): Area Under the Plasma Concentration- Time Curve From Time 0 to t for E7820 | Day 1 or 8: 0.5-48 hours | — |
| Treatment Phase Part A: Cmax: Maximum Observed Plasma Concentration for E7820 | Day 1 or 8: 0.5-48 hours | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR) | From first dose of study drug (Baseline) up to approximately 6.6 years | BOR based on RECIST 1.1 for target and non-target lesions is complete response (CR) or partial response (PR) for \>4 weeks or stable disease (SD) for \>5 weeks from first dose. CR: disappearance of target and non-target lesions, normalization of tumor marker level, all lymph nodes must be non- pathological in size (\<10 millimeter \[mm\] short axis). PR: at least 30% decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
| Extension Phase Part A, and Treatment and Extension Phase Part B: Duration of Response | From date of first documented confirmed CR/PR until date of first documentation of PD or death (approximately up to 6.6 years) | Duration of response based on RECIST 1.1 for target and non-target lesions is the time from the date of first documented confirmed CR/PR until the first documentation of confirmed progressive disease (PD) or death, whichever came first. CR: disappearance of target and non-target lesions,normalization of tumor marker level,all lymph nodes must be non-pathological in size(\<10 mm short axis). PR: at least 30% decrease in SOD of target lesions,taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. PD:at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions,taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
| Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Death and Progressive Disease (PD) | From first dose date to the date of the first documentation of confirmed PD or death (approximately up to 6.6 years) | PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions. For PD: participants with best response of PD have been reported. For Death: participants with death known to have died at any point have been reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years) | Safety assessments consisted of monitoring and recording all AEs and SAEs; regular monitoring of hematology, clinical chemistry, and urine values; physical examinations; and regular measurement of vital signs, ECG, and multiple-gated acquisition (MUGA) scans or echocardiograms. |
Countries
Netherlands, United Kingdom
Participant flow
Recruitment details
Participants took part in the study at 6 investigative sites in the Netherlands and United Kingdom from 30 June 2011 to 12 November 2017.
Pre-assignment details
In Part A, a total of 18 participants were enrolled, out of which 15 participants were randomized and treated. In Part B, a total of 27 participants were enrolled, out of which 26 participants were treated.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Phase Part A: E7820 50 mg Fed+ E7820 50 mg Fasted Participants received E7820 50 mg, tablet, orally, under fed condition on Day 1, followed by E7820 50 mg, tablet, orally, under fasted condition on Day 8. A washout period of 7 days was maintained between the doses. | 7 |
| Treatment Phase Part A: E7820 50 mg Fasted + E7820 50 mg Fed Participants received E7820 50 mg, tablet, orally, under fasted condition on Day 1, followed by E7820 50 mg, tablet, orally, under fed condition on Day 8. A washout period of 7 days was maintained between the doses. | 8 |
| Treatment Phase Part B: E7820 50 mg Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. | 19 |
| Treatment Phase Part B: E7820 60 mg Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. | 7 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Extension Phase | Adverse Event | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Extension Phase | Other | 0 | 0 | 0 | 0 | 1 | 2 | 0 |
| Treatment Phase | Adverse Event | 0 | 0 | 3 | 1 | 0 | 0 | 0 |
| Treatment Phase | Other | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Treatment Phase | Withdrawal by Subject | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Treatment Phase Part A: E7820 50 mg Fed+ E7820 50 mg Fasted | Treatment Phase Part A: E7820 50 mg Fasted + E7820 50 mg Fed | Treatment Phase Part B: E7820 50 mg | Treatment Phase Part B: E7820 60 mg | Total |
|---|---|---|---|---|---|
| Age, Customized Between 18 and 44 years | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Age, Customized Between 45 and 64 years | 5 Participants | 1 Participants | 8 Participants | 5 Participants | 19 Participants |
| Age, Customized Between 65 and 74 years | 1 Participants | 3 Participants | 9 Participants | 1 Participants | 14 Participants |
| Age, Customized Greater than (>) 74 years | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 4 Participants |
| ECOG Score 0 | 1 Participants | 4 Participants | 7 Participants | 1 Participants | 13 Participants |
| ECOG Score 1 | 5 Participants | 4 Participants | 12 Participants | 5 Participants | 26 Participants |
| ECOG Score 2 | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| ECOG Score 3 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ECOG Score 4 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ECOG Score 5 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 8 Participants | 19 Participants | 7 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Chinese | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 8 Participants | 19 Participants | 7 Participants | 40 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 6 Participants | 2 Participants | 15 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 13 Participants | 5 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 11 / 15 | 11 / 15 | 11 / 15 | 14 / 19 | 5 / 7 |
| other Total, other adverse events | 7 / 15 | 6 / 15 | 14 / 15 | 19 / 19 | 7 / 7 |
| serious Total, serious adverse events | 0 / 15 | 1 / 15 | 5 / 15 | 10 / 19 | 6 / 7 |
Outcome results
Primary
Treatment Phase Part A: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for E7820
Time frame: Day 1 or 8: 0.5-48 hours
Population: The pharmacokinetic (PK) analysis set included all participants who had sufficient PK data to derive at least 1 PK parameter. Participants who were evaluable at a particular time point for this endpoint were included in the assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Phase Part A: E7820 50 mg Fed | Treatment Phase Part A: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for E7820 | 12500 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 3510 |
| Treatment Phase Part A: E7820 50 mg Fasted | Treatment Phase Part A: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for E7820 | 11500 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 3490 |
90% CI: [0.97, 1.15]
Primary
Treatment Phase Part A: AUC(0-t): Area Under the Plasma Concentration- Time Curve From Time 0 to t for E7820
Time frame: Day 1 or 8: 0.5-48 hours
Population: The PK analysis set included all participants who had sufficient PK data to derive at least 1 PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Phase Part A: E7820 50 mg Fed | Treatment Phase Part A: AUC(0-t): Area Under the Plasma Concentration- Time Curve From Time 0 to t for E7820 | 11200 ng*hr/mL | Standard Deviation 3680 |
| Treatment Phase Part A: E7820 50 mg Fasted | Treatment Phase Part A: AUC(0-t): Area Under the Plasma Concentration- Time Curve From Time 0 to t for E7820 | 10500 ng*hr/mL | Standard Deviation 3460 |
90% CI: [1.02, 1.2]
Primary
Treatment Phase Part A: Cmax: Maximum Observed Plasma Concentration for E7820
Time frame: Day 1 or 8: 0.5-48 hours
Population: The PK analysis set included all participants who had sufficient PK data to derive at least 1 PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Phase Part A: E7820 50 mg Fed | Treatment Phase Part A: Cmax: Maximum Observed Plasma Concentration for E7820 | 1030 nanogram per milliliter (ng/mL) | Standard Deviation 311 |
| Treatment Phase Part A: E7820 50 mg Fasted | Treatment Phase Part A: Cmax: Maximum Observed Plasma Concentration for E7820 | 901 nanogram per milliliter (ng/mL) | Standard Deviation 242 |
90% CI: [1, 1.27]
Primary
Treatment Phase Part B: Maximum Tolerated Dose (MTD) of E7820 BID Dosing Schedule
MTD defined as the highest dose level at which no more than 1 of 6 participants experienced a dose-limiting toxicity(DLT), with the next higher dose having at least 2 of 3 or 2 of 6 participants experiencing DLTs. DLTs were defined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events(CTCAE) Version 4.03 as: Neutropenia less than(\<) 0.5\*10\^9/liter(L) for greater than(\>) 5 days; neutropenia \<1\*10\^9/L with fever; thrombocytopenia \<25\*10\^9/L accompanied by bleeding or thrombocytopenia \<10\*10\^9/L; any Grade 3 or 4 nonhematological toxicity for which the study drug could not be excluded as a cause (other than nausea, vomiting or diarrhea in the absence of appropriate prophylaxis) with the following clarification: Grade 3 or 4 nonhematological laboratory abnormalities for which there was no expected clinical correlation would not be considered DLTs; treatment delay of \>14 days required to recover from E7820-related toxicities.
Time frame: Up to Cycle 6 (Cycle length =28 days)
Population: MTD was assessed in safety analysis set. The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Phase Part A: E7820 50 mg Fed | Treatment Phase Part B: Maximum Tolerated Dose (MTD) of E7820 BID Dosing Schedule | 50 mg |
Secondary
Extension Phase Part A, and Treatment and Extension Phase Part B: Duration of Response
Duration of response based on RECIST 1.1 for target and non-target lesions is the time from the date of first documented confirmed CR/PR until the first documentation of confirmed progressive disease (PD) or death, whichever came first. CR: disappearance of target and non-target lesions,normalization of tumor marker level,all lymph nodes must be non-pathological in size(\<10 mm short axis). PR: at least 30% decrease in SOD of target lesions,taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. PD:at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions,taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time frame: From date of first documented confirmed CR/PR until date of first documentation of PD or death (approximately up to 6.6 years)
Population: Duration of response was not analyzed since no participants had best overall response of CR or PR in the study.
Secondary
Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR)
BOR based on RECIST 1.1 for target and non-target lesions is complete response (CR) or partial response (PR) for \>4 weeks or stable disease (SD) for \>5 weeks from first dose. CR: disappearance of target and non-target lesions, normalization of tumor marker level, all lymph nodes must be non- pathological in size (\<10 millimeter \[mm\] short axis). PR: at least 30% decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time frame: From first dose of study drug (Baseline) up to approximately 6.6 years
Population: The efficacy evaluable analysis set: all participants with a completed tumor assessment at Baseline (Chest, Abdomen and Pelvis scans) and at least 1 complete posttreatment tumor assessment (as per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1). Overall number of participants analyzed signifies participants evaluable for this measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Phase Part A: E7820 50 mg Fed | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR) | Partial response | 0 Participants |
| Treatment Phase Part A: E7820 50 mg Fed | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR) | Complete response | 0 Participants |
| Treatment Phase Part A: E7820 50 mg Fed | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR) | Stable disease | 3 Participants |
| Treatment Phase Part A: E7820 50 mg Fasted | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR) | Partial response | 0 Participants |
| Treatment Phase Part A: E7820 50 mg Fasted | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR) | Complete response | 0 Participants |
| Treatment Phase Part A: E7820 50 mg Fasted | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR) | Stable disease | 12 Participants |
| Treatment and Extension Phase Part B: E7820 60 mg | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR) | Complete response | 0 Participants |
| Treatment and Extension Phase Part B: E7820 60 mg | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR) | Stable disease | 2 Participants |
| Treatment and Extension Phase Part B: E7820 60 mg | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR) | Partial response | 0 Participants |
Secondary
Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Death and Progressive Disease (PD)
PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions. For PD: participants with best response of PD have been reported. For Death: participants with death known to have died at any point have been reported.
Time frame: From first dose date to the date of the first documentation of confirmed PD or death (approximately up to 6.6 years)
Population: The efficacy evaluable set. Due to lack of available summarized data, data has been presented only descriptively in terms of number of participants who were known to have died and number of who had PD.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Phase Part A: E7820 50 mg Fed | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Death and Progressive Disease (PD) | Death | 11 Participants |
| Treatment Phase Part A: E7820 50 mg Fed | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Death and Progressive Disease (PD) | PD | 9 Participants |
| Treatment Phase Part A: E7820 50 mg Fasted | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Death and Progressive Disease (PD) | Death | 14 Participants |
| Treatment Phase Part A: E7820 50 mg Fasted | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Death and Progressive Disease (PD) | PD | 6 Participants |
| Treatment and Extension Phase Part B: E7820 60 mg | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Death and Progressive Disease (PD) | Death | 5 Participants |
| Treatment and Extension Phase Part B: E7820 60 mg | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Death and Progressive Disease (PD) | PD | 2 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Safety assessments consisted of monitoring and recording all AEs and SAEs; regular monitoring of hematology, clinical chemistry, and urine values; physical examinations; and regular measurement of vital signs, ECG, and multiple-gated acquisition (MUGA) scans or echocardiograms.
Time frame: From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Phase Part A: E7820 50 mg Fed | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 7 Participants |
| Treatment Phase Part A: E7820 50 mg Fed | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Treatment Phase Part A: E7820 50 mg Fasted | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 7 Participants |
| Treatment Phase Part A: E7820 50 mg Fasted | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| Treatment and Extension Phase Part B: E7820 60 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 15 Participants |
| Treatment and Extension Phase Part B: E7820 60 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 5 Participants |
| Treatment and Extension Phase Part B: E7820 50 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 10 Participants |
| Treatment and Extension Phase Part B: E7820 50 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 19 Participants |
| Treatment and Extension Phase Part B: E7820 60 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 7 Participants |
| Treatment and Extension Phase Part B: E7820 60 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 6 Participants |