Phase II Study of Pembrolizumab in Combination With Lenvatinib in Patients With TNBC, NSCLC, and Other Tumor Types and Brain Metastases

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).