A Trial of Lenvatinib (E7080) Plus Pembrolizumab in Participants With Selected Solid Tumors
Source: ClinicalTrials.gov NCT02501096 ↗Summary
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Lenvatinib |
20; 20 | — |
| PRIMARY Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs) of Lenvatinib |
1; 1; 0; 0; 0; 0 | — |
| PRIMARY Objective Response Rate (ORR) Based on Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) Version 1.1 at Week 24 |
39.5; 56.6; 47.6; 23.8; 31.8; 25.0 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) |
2; 1; 124; 145; 21; 21 | — |
| SECONDARY Objective Response Rate (ORR) Based on irRECIST Version 1.1 |
40.3; 63.4; 47.6; 23.8; 40.9; 25.0 | — |
| SECONDARY Progression-free Survival (PFS) Based on irRECIST Version 1.1 |
7.5; 14.1; 5.5; 5.4; 4.4; 5.4 | — |
| SECONDARY Overall Survival (OS) |
19.9; 32.2; 25.4; 11.4; 16.2; 6.1 | — |
| SECONDARY Disease Control Rate (DCR) Based on irRECIST Version 1.1 |
84.7; 93.8; 81.0; 76.2; 90.9; 70.0 | — |
| SECONDARY Clinical Benefit Rate (CBR) Based on irRECIST Version 1.1 |
58.9; 80.0; 61.9; 57.1; 45.5; 40.0 | — |
| SECONDARY Durable Stable Disease Rate (DSDR) Based on irRECIST Version 1.1 |
— | — |
| SECONDARY Duration of Objective Response (DOR) Based on irRECIST Version 1.1 |
NA; 16.6; 12.5; 14.5; 7.1; 41.0 | — |
| SECONDARY Phase 1b: Plasma Concentrations of Lenvatinib |
102.5; 198.0; 210.5; 53.9; 1.8; 78.4 | — |
| SECONDARY Plasma Concentrations of Lenvatinib |
82.2; 35.5; 24.0; 79.9; 41.8; 123.8 | — |
Eligibility Criteria
Inclusion Criteria
- Phase 1b: Histologically and/or cytologically confirmed metastatic selected solid tumor types that have progressed after treatment with approved therapies or for which there are no standard effective therapies available. If nivolumab or pembrolizumab is an approved therapy for the participant's tumor type, but the participant has not been treated with it, the Investigator may enroll the participant in this study.
Phase 2: Histologically and/or cytologically confirmed metastatic selected solid tumor types with 0-2 prior lines of systemic therapy. If previously treated, participant has progressed after previous treatment. For the non-small cell lung cancer (NSCLC) and melanoma cohorts, participants must have progressed on or after prior treatment with one anti-programmed cell death protein 1 (anti-PD-1), anti-PD-1 ligand 1 (anti-PD-L1), or anti-PD-1 ligand 2 (anti-PD-L2) agent. For the renal cell carcinoma (RCC) cohort, participants must have progressed on treatment with an anti- programmed death receptor-1 /programmed death receptor-ligand 1 monoclonal antibody (anti-PD-1/PD-L1 mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies, the regimen with an anti-PD-1/PD-L1 mAb must be the most recent therapy. Selected tumor types of both phases: NSCLC, predominantly clear cell renal cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, or melanoma (excluding uveal melanoma)
- Life expectancy of 12 weeks or more
- Phase 2: Measurable disease meeting the following criteria:
- At least 1 lesion of greater than or equal to 10 mm in the longest diameter for a non-lymph node or greater than or equal to 15 mm in the short-axis diameter for a lymph node that is serially measurable according to irRECIST (immune-related Response Evaluation Criteria in Solid Tumors) using computerized tomography/magnetic resonance imaging (CT/MRI)
- Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show subsequent evidence of substantial size increase to be deemed a target lesion
- Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
- Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal to 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Cycle 1 Day 1
- Adequate renal function defined as creatinine less than or equal to 1.5*ULN (upper limit of normal) or calculated creatinine clearance greater than or equal to 40 mL/min per the Cockcroft and Gault formula with creatinine levels greater than 1.5*ULN
- Adequate bone marrow function:
- Absolute neutrophil count (ANC) greater than or equal to 1500/mm3 (greater than or equal to 1.5 X 103/uL)
- Platelets greater than or equal to 100,000/mm3 (greater than or equal to 100 X 109/L)
- Hemoglobin greater than or equal to 9.0 g/dL
- Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) less than or equal to 1.5
- Adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the ULN and alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3*ULN (in the case of liver metastases less than or equal to 5*ULN). In case ALP is greater than 3 X ULN (in the absence of liver metastases) or greater than 5 X ULN (in the presence of liver metastases) AND the participant also is known to have bone metastases, the liver specific ALP must be separated from the total and used to assess the liver function instead of the total ALP
- Males or females age greater than or equal to 18 years at the time of informed consent
- Participants with known brain metastases will be eligible if they have completed the primary brain therapy (such as wh
Data sourced from ClinicalTrials.gov (NCT02501096). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.