NCT07011849

Study of Lenvatinib Plus Pembrolizumab in IO Refractory mRCC Patients With Brain Metastases

A Multi-center, Open-label Phase II Study of Lenvatinib Plus Pembrolizumab (LEAP) in Renal Cell Carcinoma Patients With Brain Metastasis Previously Treated With Immune Checkpoint Blockade

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multi-center, open-label phase II study evaluating the efficacy and safety of pembrolizumab in combination with lenvatinib in patients with renal cell carcinoma (RCC) and brain metastasis who were previously treated with immune checkpoint blockade.

Detailed description

Primary Objectives: Primary Objective: To determine the intracranial PFS of pembrolizumab plus lenvatinib in IO refractory mRCC participants with brain metastases per Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) criteria (Appendix 1). Hypothesis: Investigators hypothesize that pembrolizumab plus lenvatinib will provide a higher intracranial PFS in RCC participants with brain metastases when compared to historical data. Primary Endpoint: intracranial PFS per RANO-BM criteria. Secondary Objectives: * To determine the intracranial ORR in participants with remaining non-irradiated brain metastases, as assessed by RANO-BM criteria. * To determine the local control rate in participants with irradiated brain metastases at 1 year, as assessed by RANO-BM criteria. * To determine the rate of new brain metastasis at a site different from the original brain metastases at 1 year (Distant brain failure rate), as assessed by RANO-BM criteria. * To determine the intracranial disease control rate: complete response + partial response + stable disease (DCR: CR + PR + SD) in participants with remaining non-irradiated brain metastases, as assessed by RANO-BM. * To determine the intracranial clinical benefit rate (CBR: CR + PR + .6 months SD) in participants with remaining non-irradiated brain metastases, as assessed by RANO-BM. * To determine the intracranial duration of response (DOR) in participants with remaining nonirradiated brain metastases, as assessed by the RANO-BM. * To determine the time to response (TTR) in participants with remaining non-irradiated brain metastases, as assessed by the RANO-BM. * To evaluate the safety and tolerability, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 (Appendix 9). * To define symptomatic radiation necrosis rate defined as the rate of clinical symptomatology requiring steroid administration and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. * To determine the extracranial ORR, as assessed by the Modified Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1). * To determine extracranial PFS, as assessed by the RECIST 1.1 and iRECIST. * To determine bi-compartmental PFS, as assessed by RECIST 1.1 and iRECIST for extracranial disease and RANO-BM for intracranial disease. * To evaluate OS. Secondary Endpoints: * Intracranial OR in participants with remaining non-irradiated brain metastases, as assessed by RANO-BM criteria. * Local control rate in participants with irradiated brain metastases at 1 year, as assessed by RANO-BM criteria. * Distant brain failure rate, the rate of new brain metastasis at a site different from the original brain metastases at 1 year, as assessed by RANO-BM criteria. * Intracranial disease contro (CR + PR + SD) in participants with remaining non-irradiated brain metastases, as assessed by RANO-BM. * Intracranial clinical benefit (CR + PR + .6 months SD) in participants with remaining nonirradiated brain metastases, as assessed by RANO-BM. * Intracranial duration of response (DOR) in participants with remaining non-irradiated brain metastases, as assessed by the RANO-BM. * Time to response (TTR) in participants with remaining non-irradiated brain metastases, as assessed by the RANO-BM. * Safety and tolerability, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. * Symptomatic radiation necrosis rate defined as the rate of clinical symptomatology requiring steroid administration and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. * Extracranial OR, as assessed by the RECIST 1.1 and iRECIST. * Extracranial PFS, as assessed by the RECIST 1.1 and iRECIST. * Bi-compartmental PFS, as assessed by RECIST 1.1 and iRECIST for extracranial disease and RANO-BM for intracranial disease. * Overall survival (OS).

Conditions

• Renal Cell Carcinoma
• Brain Metastasis

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Given by IV
DRUG	Lenvatinib	Given by mouth

Timeline

• Start date: 2025-06-04
• Primary completion: 2025-08-07
• Completion: 2025-08-07
• First posted: 2025-06-10
• Last updated: 2025-08-13

Regulatory

• FDA-regulated drug study