Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Melanoma

Glioblastoma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Lenvatinib

Bevacizumab

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants with unresectable advanced or metastatic solid tumors will receive E7050 in combination with lenvatinib to identify a Maximum Tolerated Dose. Dose escalation will begin at low doses of both E7050 and lenvatinib, and then gradually increase in future cohorts until a recommended combination dose is identified. A dose of E7050 and lenvatinib to be used in combination in Phase 2 will be recommended (RP2 dose). Participants will continue on treatment until disease progression, development of unacceptable toxicity, or withdrawal of consent.

Participants with recurrent glioblastoma (bevacizumab-naïve) will receive E7050 and lenvatinib at the RP2 dose.

Participants with recurrent glioblastoma (bevacizumab-naïve) will receive single agent lenvatinib 24 mg/day (1\*4 mg capsule + 2\*10 mg capsule) and at time of progression, E7050 add-on therapy at the RP2 dose (in combination with lenvatinib at dose of either the RP2 dose or the most recent dose of single agent lenvatinib, whichever is the lowest).

Participants with unresectable Stage III or Stage IV melanoma and disease progression after prior systemic treatment will receive E7050 and lenvatinib at the RP2 dose.

Participants with unresectable Stage III or Stage IV melanoma and disease progression after prior systemic treatment will receive single agent E7050 400 mg/day.

Participants will receive E7050 50 mg and/or 100 mg tablets. E7050 will be administered orally once daily, in 28-day cycles.

Golvatinib

Participants will receive lenvatinib 1 mg and/or 4 mg and/or 10 mg capsules. Lenvatinib will be administered orally once daily, in 28-day cycles.

Participants will receive lenvatinib 24 mg (1\*4 mg capsule + 2\*10 mg capsule) capsules. Lenvatinib will be administered orally once daily, in 28-day cycles.

This is a multicenter, open-label, Phase 1b/2 study which will be conducted in two parts: a Phase 1b part comprising a dose escalation and an expansion cohort; and a Phase 2 part which will comprise two cohorts. The purpose of the Phase 1b part is to identify the maximum tolerated dose (MTD) of E7050 and E7080 (lenvatinib) in combination in participants with unresectable advanced or metastatic solid tumors. In the subsequent Phase 1b expansion cohort and Phase 2 cohorts, additional participants with recurrent glioblastoma or unresectable Stage III or Stage IV melanoma and disease progression after prior systemic treatment will be enrolled to confirm the MTD (expansion cohort) and to further explore the clinical activity of E7050 and lenvatinib.

A Study of E7050 in Combination With E7080 in Participants With Advanced Solid Tumors (Dose Escalation) and in Participants With Recurrent Glioblastoma or Unresectable Stage III or Stage IV Melanoma After Prior Systemic Therapy (Expansion Cohort and Phase 2)

An Open-Label, Multicenter Phase 1b/2 Study of E7050 in Combination With E7080 in Subjects With Advanced Solid Tumors (Dose Escalation) and in Subjects With Recurrent Glioblastoma or Unresectable Stage III or Stage IV Melanoma After Prior Systemic Therapy (Expansion Cohort and Phase 2)

DLT was defined as toxicity related to the combination therapy and was graded according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Hematological DLTs were Grade 4 neutropenia for greater than or equal to (\>=) 7 days or Grade 3 neutropenia with fever (greater than \[\>\] 38.5 degree Celsius (°C) in axilla), Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding or lasting \>7 days and decrease of hemoglobin of Grade 4. Non-hematological DLTS were Grade 3 fatigue, or a 2 point decline in Eastern Cooperative Oncology Group (ECOG) performance status must persist for \>7days, Nausea, vomiting or diarrhea must persist at Grade 3 or 4 despite maximal medical therapy, Grade 4 hypertension or Grade 3 hypertension not able to be controlled by medication and any Grade 3 or higher non-hematological laboratory abnormalities that require hospitalization.

The MTD was defined as the highest dose level at which no more than 1/6 participants experienced a DLTs, with the next higher dose having at least 0 of 3 or 1 of 6 participants experiencing DLTs. MTD was determined by summarizing the number and percentage of participants with DLTs for the first cycle, by study dosing schedule, initial dosing level and overall for the dose escalation part. The RP2D of golvatinib in Combination with lenvatinib was MTD determined by Dose Escalation Committee (DEC) based on safety, PK and clinical data. DLT was defined as toxicity related to the combination therapy and was graded according to CTCAE v4.0.

The MTD was defined as the highest dose level at which no more than 1/6 participants experienced a DLTs, with the next higher dose having at least 0 of 3 or 1 of 6 participants experiencing DLTs. MTD was determined by summarizing the number and percentage of participants with DLTs for the first cycle, by study dosing schedule, initial dosing level and overall for the dose escalation part. The RP2D of lenvatinib in Combination with golvatinib was MTD determined by DEC based on safety, PK and clinical data. DLT was defined as toxicity related to the combination therapy and was graded according to CTCAE v4.0.

ORR was assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. ORR was defined as the percentage of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (\<)10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Eisai Inc.

Participants received lenvatinib 12 mg capsules, orally, once on Day -8, followed by golvatinib 200 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).

Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg

Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 200 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).

Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg

Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 300 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).

Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg

Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 400 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).

Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg

Total

Age, Continuous

Sex: Female, Male

White

Asian

Other

Race/Ethnicity, Customized

The safety analysis set (combination treatment) included all participants who received at least 1 dose of combination treatment and had at least 1 postbaseline safety evaluation.

The study was terminated by the sponsor at the end of Phase 1b due to a change in corporate strategy, hence Phase 2 was not carried out.

Eisai Medical Information

Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).

Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).

Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).

Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).

The safety analysis set (combination treatment) included all participants who received at least 1 dose of combination treatment and had at least 1 postbaseline safety evaluation. Here, overall number analyzed "N" were the participants who were evaluable for the outcome measure.

Phase 1b: Number of Participants Who Experienced Any Dose Limiting Toxicity (DLT)- Combination Treatment

RP2D

Eligible participants from single agent run-in period, received lenvatinib 12 mg or 20 mg capsules, orally, once daily in combination with golvatinib 200 mg or 300 mg or 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).

All Cohorts: Golvatinib + Lenvatinib

Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Golvatinib in Combination With Lenvatinib

All Cohorts: Lenvatinib + Golvatinib

Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Lenvatinib in Combination With Golvatinib

Phase 1b: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values- Combination Treatment

Phase 1b: Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values- Combination Treatment

Baseline and post-baseline data

At least 1 post-baseline increase of greater than (>) 30 millisecond (msec)

At least 1 post-baseline increase of > 60 msec

At least 1 post-baseline value of > 450 msec

At least 1 post-baseline value of > 480 msec

At least 1 post-baseline value of > 500 msec

Phase 1b: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Values- Combination Treatment

TEAEs

SAEs

Phase 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)- Combination Treatment

The pharmacokinetic (PK) analysis set included participants who had at least 1 evaluable plasma concentration.

Phase 1b: Cmax; Maximum Observed Plasma Concentration for Golvatinib When Administered as a Single Agent at Day -7

The PK analysis set included participants who had at least 1 evaluable plasma concentration.

Phase 1b: Cmax; Maximum Observed Plasma Concentration for Lenvatinib When Administered as a Single Agent at Day -8

Phase 1b: Tmax; Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered as a Single Agent at Day -7

Phase 1b: Tmax; Time to Reach the Maximum Plasma Concentration (Cmax) for Lenvatinib When Administered as a Single Agent at Day -8

The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here, overall number analyzed "N" were the participants who were evaluable for the outcome measure.

Phase 1b: AUC24; Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Golvatinib When Administered as Single Agent at Day -7

Phase 1b: AUC24; Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Lenvatinib When Administered as Single Agent at Day -8

Phase 1b: AUCt; Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib When Administered as Single Agent at Day -7

PK analysis set included participants who had at least 1 evaluable plasma concentration.

Phase 1b: AUCt; Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Lenvatinib When Administered as Single Agent at Day -8

PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure.

Phase 1b: AUC∞; Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value for the Last Quantifiable Concentration for Golvatinib When Administered as Single Agent at Day -7

Phase 1b: AUC∞; Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value for the Last Quantifiable Concentration for Lenvatinib When Administered as Single Agent at Day -8

The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure.

Phase 1b: t1/2; Terminal Elimination Half-life for Golvatinib When Administered as Single Agent at Day -7

Phase 1b: t1/2; Terminal Elimination Half-life for Lenvatinib When Administered as Single Agent at Day -8

Phase 1b: CL/F; Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration for Golvatinib When Administered as Single Agent at Day -7

Phase 1b: CL/F; Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration for Lenvatinib When Administered as Single Agent at Day -8

Phase 1b: Vz/F; Apparent Volume of Distribution at Terminal Phase for Golvatinib When Administered as Single Agent at Day -7

Phase 1b: Vz/F; Apparent Volume of Distribution at Terminal Phase for Lenvatinib When Administered as Single Agent at Day -8

Golvatinib: Cycle 1 Day 1

Lenvatinib: Cycle 1 Day 1

PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given time points.

Phase 1b: Cmax; Maximum Observed Plasma Concentration for Golvatinib and Lenvatinib When Administered in Combination Treatment as Single Dose on Day 1 Cycle 1

Golvatinib: Cycle 2 Day 1

Lenvatinib: Cycle 2 Day 1

Phase 1b: Cmax; Maximum Observed Plasma Concentration for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2

The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given time points.

Phase 1b: Tmax; Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib and Lenvatinib When Administered in Combination Treatment as Single Dose on Day 1 Cycle 1

Phase 1b: Tmax; Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2

Phase 1b: AUC24; Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Golvatinib and Lenvatinib When Administered in Combination Treatment as Single Dose on Day 1 Cycle 1

Phase 1b: AUC24; Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2

The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given time points.

Phase 1b: AUCt; Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib and Lenvatinib When Administered in Combination Treatment as Single Dose on Day 1 Cycle 1

Phase 1b: AUCt; Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2

Phase 1b: CLss/F; Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2

Phase 1b: Rac(AUC); Accumulation Ratio Based on AUC Calculated as AUC24 at Steady State/AUC24 for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2

Phase 1b: Rac(Cmax); Accumulation Ratio Based on Cmax Calculated as Cmax at Steady State/Cmax for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2

Safety analysis set (combination treatment) included all participants who received at least 1 dose of combination treatment and had at least 1 postbaseline safety evaluation.

Phase 1b: Objective Response Rate (ORR); Combination Treatment

Participants received lenvatinib 12 milligram (mg) capsules, orally, once on Day -8, followed by golvatinib 200 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).

Spots Global Cancer Trial Database for A Study of E7050 in Combination With E7080 in Participants With Advanced Solid Tumors (Dose Escalation) and in Participants With Recurrent Glioblastoma or Unresectable Stage III or Stage IV Melanoma After Prior Systemic Therapy (Expansion Cohort and Phase 2)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

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