Solid Tumors
Conditions
Keywords
lenvatinib, E7080
Brief summary
This study will be conducted to assess the long-term safety of study drug(s) in participants who are enrolled in Eisai-sponsored lenvatinib studies.
Detailed description
This is an open-label extension study to roll-over eligible participants from Eisai-sponsored lenvatinib studies. The participants may roll-over no sooner than the primary completion dates in their parent study or after all study data for the primary outcome measure have been collected for the parent study. The parent study is defined as the Eisai-sponsored lenvatinib clinical study in which the participant was receiving lenvatinib either as monotherapy or as combination therapy or was receiving any other comparator therapy. The participant can be enrolled in the current study for the purpose of long-term safety data collection if all the selection criteria for the current study are met. The intention is that the participant will not be without study drug during the transition from the parent study to the rollover study.
Interventions
DRUGE7080
Oral Administration.
DRUGComparator Drug
Per parent study.
DRUGComparator Drug: Sorafenib
Per parent study.
Sponsors
Merck Sharp & Dohme LLC
Eisai Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
It is required for all participants currently participating in other lenvatinib studies to meet the following eligibility criteria. * Provide signed written informed consent for the roll-over study * Currently enrolled in an Eisai-sponsored lenvatinib clinical study and still receiving at least one of the study drugs from that protocol * Currently deriving clinical benefit from at least one of the study drug(s) as determined by the investigator * Must be able and willing to comply with the current roll-over protocol requirements * Continued ability to swallow and retain orally administered study drug(s) * Does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels * Women of childbearing potential and men with reproductive potential (if specified by the parent study) must be willing to continue to use highly effective methods of contraception as per local practices of standard of care during the period of the study * Women of childbearing potential must have a negative serum pregnancy test at the time of transition to the study and before continuing study drug(s)
Exclusion criteria
* Permanent discontinuation of all study drug(s) in the parent study due to toxicity or disease progression and without clinical benefit * Receiving any prohibited medication(s) as described in the parent study * Any unresolved toxicity that meets the criteria for study drug(s) discontinuation or withdrawal criteria from the parent study at the time of transition to this study * Uncontrolled diabetes, hypertension or other medical conditions at the time of transition to the roll-over study that may interfere with assessment of toxicity * Pregnant or lactating female * Any serious and/or unstable pre-existing medical condition, psychiatric disorder or other conditions at the time of transition to the roll-over study that could interfere with participant's safety in the opinion of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Treatment-Emergent Serious Adverse Events (TESAEs) | Up to 58.8 months in current study | A treatment-emergent adverse events (TEAE) was defined as an adverse event (AE) that emerged during the treatment in the current roll-over study, having been absent prior to the time the participant signed the current roll-over study informed consent form (ICF), or re-emerged during treatment in the current roll-over study after having been present but resolved before signing the ICF or worsened in severity during treatment in the current roll-over study relative to the pre-ICF state, when the AE was continuous. A serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically important due to other reasons than the mentioned criteria. |
| Number of Participants With Any Non-Serious Treatment-Emergent Adverse Events (TEAEs) | Up to 58.8 months in current study | A TEAE was defined as an AE that emerged during the treatment in the current roll-over study, having been absent prior to the time the participant signed the current roll-over study in ICF, or re-emerged during treatment in the current roll-over study after having been present but resolved before signing the ICF or worsened in severity during treatment in the current roll-over study relative to the pre-ICF state, when the AE was continuous. A non-serious TEAE was any AE that was not considered a serious adverse event. |
| Number of Participants With Treatment-Related TEAEs | Up to 58.8 months in current study | A TEAE was defined as an AE that emerged during the treatment in the current roll-over study, having been absent prior to the time the participant signed the current roll-over study ICF, or re-emerged during treatment in the current roll-over study after having been present but resolved before signing the ICF or worsened in severity during treatment in the current roll-over study relative to the pre-ICF state, when the AE was continuous. Related TEAE was defined as AE with causal relationship between the study drug and the TEAE. |
| Number of Participants With Any TEAE | Up to 58.8 months in current study | A TEAE was defined as an AE that emerged during the treatment in the current roll-over study, having been absent prior to the time the participant signed the current roll-over study ICF, or re-emerged during treatment in the current roll-over study after having been present but resolved before signing the ICF or worsened in severity during treatment in the current roll-over study relative to the pre-ICF state, when the AE was continuous. |
Countries
Australia, Belgium, China, Germany, Italy, Netherlands, Poland, Romania, South Korea, Thailand, United States
Participant flow
Recruitment details
Participants took part in the study at 28 investigative sites in China, United States, Australia, Belgium, Germany, Italy, South Korea, Netherlands, Poland, Romania, and Thailand from 16 August 2018 to 21 December 2023.
Pre-assignment details
A total of 40 participants were screened and enrolled to receive study treatment in this rollover study. The study was to consist of Cohorts A, B and C; however, no participants met criteria for Cohorts B or C, so no participants were enrolled in these cohorts and hence no data were collected and reported for these cohorts. As pre-specified in statistical analysis plan (SAP), data were collected and reported by regions (China and Rest of World) in this study for all sections.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A, China: Lenvatinib Monotherapy Participants from China who received lenvatinib monotherapy or who crossed over from a comparator arm to receive lenvatinib monotherapy in their parent study (E7080-C086-108 \[NCT03009292\], or E7080-C086-308 \[NCT02966093\]) received lenvatinib dose ranging from 4 mg to 24 mg, capsules, orally until PD, unacceptable toxicity, participant's discontinued study, use of nonpermitted concomitant drug, unacceptable noncompliance with the protocol, or lost to follow-up. | 19 |
| Cohort A, Rest of the World: Lenvatinib Monotherapy Participants from rest of the world who received lenvatinib monotherapy or who crossed over from a comparator arm to receive lenvatinib monotherapy in their parent study (E7080-E044-101 \[NCT00121719\], E7080-A001-109 \[NCT02686164\], E7080-G000-201 \[NCT00784303\], E7080-G000-303 \[NCT01321554\], E7080-C086-108 \[NCT03009292\], or E7080-C086-308 \[NCT02966093\]) received lenvatinib dose ranging from 4 mg to 24 mg, capsules, orally until PD, unacceptable toxicity, participant's discontinued study, use of nonpermitted concomitant drug, unacceptable noncompliance with the protocol, or lost to follow-up. | 21 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 5 |
| Overall Study | Disease Progression | 7 | 7 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Transitioned to commercial drug | 6 | 6 |
| Overall Study | Unable to travel due to COVID-19 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Cohort A, Rest of the World: Lenvatinib Monotherapy | Total | Cohort A, China: Lenvatinib Monotherapy |
|---|---|---|---|
| Age, Continuous | 62.7 years STANDARD_DEVIATION 11.45 | 59.6 years STANDARD_DEVIATION 10.42 | 56.2 years STANDARD_DEVIATION 8.17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 40 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 23 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 17 Participants | 0 Participants |
| Sex: Female, Male Female | 12 Participants | 21 Participants | 9 Participants |
| Sex: Female, Male Male | 9 Participants | 19 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 19 | 5 / 21 |
| other Total, other adverse events | 18 / 19 | 17 / 21 |
| serious Total, serious adverse events | 7 / 19 | 14 / 21 |
Outcome results
Primary
Number of Participants With Any Non-Serious Treatment-Emergent Adverse Events (TEAEs)
A TEAE was defined as an AE that emerged during the treatment in the current roll-over study, having been absent prior to the time the participant signed the current roll-over study in ICF, or re-emerged during treatment in the current roll-over study after having been present but resolved before signing the ICF or worsened in severity during treatment in the current roll-over study relative to the pre-ICF state, when the AE was continuous. A non-serious TEAE was any AE that was not considered a serious adverse event.
Time frame: Up to 58.8 months in current study
Population: Safety analysis set included the group of participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A, China: Lenvatinib Monotherapy | Number of Participants With Any Non-Serious Treatment-Emergent Adverse Events (TEAEs) | 18 Participants |
| Cohort A, Rest of the World: Lenvatinib Monotherapy | Number of Participants With Any Non-Serious Treatment-Emergent Adverse Events (TEAEs) | 17 Participants |
Primary
Number of Participants With Any TEAE
A TEAE was defined as an AE that emerged during the treatment in the current roll-over study, having been absent prior to the time the participant signed the current roll-over study ICF, or re-emerged during treatment in the current roll-over study after having been present but resolved before signing the ICF or worsened in severity during treatment in the current roll-over study relative to the pre-ICF state, when the AE was continuous.
Time frame: Up to 58.8 months in current study
Population: Safety analysis set included the group of participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A, China: Lenvatinib Monotherapy | Number of Participants With Any TEAE | 18 Participants |
| Cohort A, Rest of the World: Lenvatinib Monotherapy | Number of Participants With Any TEAE | 20 Participants |
Primary
Number of Participants With Any Treatment-Emergent Serious Adverse Events (TESAEs)
A treatment-emergent adverse events (TEAE) was defined as an adverse event (AE) that emerged during the treatment in the current roll-over study, having been absent prior to the time the participant signed the current roll-over study informed consent form (ICF), or re-emerged during treatment in the current roll-over study after having been present but resolved before signing the ICF or worsened in severity during treatment in the current roll-over study relative to the pre-ICF state, when the AE was continuous. A serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically important due to other reasons than the mentioned criteria.
Time frame: Up to 58.8 months in current study
Population: Safety analysis set included the group of participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A, China: Lenvatinib Monotherapy | Number of Participants With Any Treatment-Emergent Serious Adverse Events (TESAEs) | 7 Participants |
| Cohort A, Rest of the World: Lenvatinib Monotherapy | Number of Participants With Any Treatment-Emergent Serious Adverse Events (TESAEs) | 14 Participants |
Primary
Number of Participants With Treatment-Related TEAEs
A TEAE was defined as an AE that emerged during the treatment in the current roll-over study, having been absent prior to the time the participant signed the current roll-over study ICF, or re-emerged during treatment in the current roll-over study after having been present but resolved before signing the ICF or worsened in severity during treatment in the current roll-over study relative to the pre-ICF state, when the AE was continuous. Related TEAE was defined as AE with causal relationship between the study drug and the TEAE.
Time frame: Up to 58.8 months in current study
Population: Safety analysis set included the group of participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A, China: Lenvatinib Monotherapy | Number of Participants With Treatment-Related TEAEs | 15 Participants |
| Cohort A, Rest of the World: Lenvatinib Monotherapy | Number of Participants With Treatment-Related TEAEs | 14 Participants |