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Clinical Trial Summary

This is a single-center, open-label, multi-cohort Phase II study evaluating the efficacy and safety of pembrolizumab in combination with lenvatinib in patients with solid tumors and brain metastases. The study will be comprised of 3 patient cohorts: triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), and solid tumor types other than TNBC and NSCLC. Cohort 3 will be comprised of solid tumor types with established (e.g., renal cell carcinoma [RCC], endometrial cancer) or preliminary clinical evidence (e.g., gastric cancer, colorectal cancer) of efficacy of programmed cell death-1 (PD-1) and angiogenesis inhibitors. The study will be conducted using a Simon's optimal two-stage design, and approximately 87 patients will be enrolled concurrently (n=29 per cohort). The primary endpoint is intracranial objective response rate (ORR) as assessed by the modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.


Clinical Trial Description

Primary Objective: Objective: To determine the intracranial ORR of the pembrolizumab and lenvatinib combination in patients with TNBC or NSCLC and brain metastases, as assessed according to the modified RECIST (mRECIST) [Qianet al., 2017] (Appendix 1). Secondary Objectives: - Objective: To evaluate the safety and tolerability of the pembrolizumab and lenvatinib combination in patients with TNBC, NSCLC, and other solid tumor types and brain metastases, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. (Appendix 2). - To determine the intracranial ORR of the pembrolizumab and lenvatinib combination in patients with TNBC or NSCLC and brain metastases, as assessed according to the Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) criteria (Appendix 3). - Objective: To determine intracranial progression-free survival (PFS) of the pembrolizumab and lenvatinib combination in patients with TNBC, NSCLC, and other solid tumor types --Objective: To determine the systemic ORR of the pembrolizumab and lenvatinib combination in patients with TNBC, NSCLC, and other solid tumor types and brain metastases, as assessed by the RECIST v1.1 (Appendix 4). - Objective: To evaluate systemic PFS in patients with TNBC, NSCLC, and other solid tumor types and brain metastases receiving the pembrolizumab and lenvatinib combination, as assessed by the RECIST v1.1. - Objective: To evaluate overall survival (OS) in patients with TNBC, NSCLC, and other solid tumor types and brain metastases receiving the pembrolizumab and lenvatinib combination. Exploratory Objectives - Objective: To identify the site of first progression. - Objective: To determine changes in dose, duration, and frequency of steroid use for symptomatic management of brain metastases. Patients who require at least 4 mg of dexamethasone/day for symptom management will be considered as requiring high-dose steroids. - Objective: To assess neurological function according to the Neurologic Assessment in Neuro-Oncology (NANO) scale (Appendix 5). - Objective: To evaluate immune-related biomarkers of response to the pembrolizumab and lenvatinib combination. - Objective: To identify imaging characteristics associated with pembrolizumab and lenvatinib treatment-induced immunological changes. - Objective: To evaluate the effects of the pembrolizumab and lenvatinib combination on cranial radiation and opiate pain medication use and seizure reduction. - Objective: Intracranial and systemic duration of response (DOR) in patients who achieve partial response (PR) or complete response (CR). ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05064280
Study type Interventional
Source M.D. Anderson Cancer Center
Contact Jordi Rodon Ahnert, MD, PhD
Phone (713) 792-5603
Email [email protected]
Status Not yet recruiting
Phase Phase 2
Start date December 31, 2021
Completion date April 30, 2023

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