A Phase 2 Trial of Pembrolizumab Plus Bevacizumab in Patients With Metastatic Melanoma or Non-small Cell Lung Cancer With Untreated Brain Metastases

Yale University2 sites in 1 country41 target enrollmentMay 1, 2016

ConditionsMelanoma Non-small Cell Lung Cancer Brain Metastasis

InterventionsPembrolizumab plus Bevacizumab

Overview

Phase: Phase 2
Intervention: Pembrolizumab plus Bevacizumab
Conditions: Melanoma
Sponsor: Yale University
Enrollment: 41
Locations: 2
Primary Endpoint: Brain Metastasis Response Rate (BMRR)
Status: Completed
Last Updated: 8 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this phase 2 trial is to study the activity of pembrolizumab in combination with bevacizumab in patients with untreated brain metastases from melanoma or NSCLC to determine activity and safety of the drug combination. Furthermore, in patients who undergo resection of biopsy of a brain metastasis, we will evaluate biomarkers predictive of treatment benefit, and will also conduct correlative biomarker studies on extra-cerebral specimens in all patients in whom a systemic biopsy is feasible or in archival tumor tissue when available.

A total of 53 eligible patients will be enrolled on this trial (40 with melanoma and 13 with NSCLC). Individual cohorts of the study can be stopped if insufficient activity is observed in the first stage of that cohort. The study will accrue for approximately 84 months, and will be open for approximately 12 additional months as patients on study are being followed.

Registry

clinicaltrials.gov

Start Date

May 1, 2016

End Date

March 31, 2025

Last Updated

8 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Yale University

Responsible Party

Principal Investigator

Harriet Kluger

Principal Investigator

Yale University

Eligibility Criteria

Inclusion Criteria

•Biopsy proven metastatic melanoma or non-squamous NSCLC with at least one untreated brain metastasis that is at least 5 mm AND twice the MRI slice thickness, but less than 20 mm, which is asymptomatic and not requiring immediate local therapy or steroids.
•Patients who have had prior resection or biopsy of a CNS metastasis will be required to provide a paraffin embedded specimen from tumor taken at the time of surgery, if available.
•Patients will be required to undergo biopsy or submit archival tumor tissue from a systemic site of disease for correlative studies. When not feasible, this requirement can be waived after discussion with the principal investigators.
•PD-L1 expression in tumor tissue from any site determined by the Dako 22C3 assay is required for patients with NSCLC.
•Adequate organ function.
•ECOG performance status \<
•Any number of previous treatments with the exception of previous inhibitors of PD-1 or PD-L
•Life expectancy of at least 3 months.
•Understanding and willingness to consent.
•A history of radiotherapy for brain metastases is allowed, but any lesion present at the time of WBRT or included in the stereotactic radiotherapy field will NOT be considered evaluable unless documented to have progressed since treatment.

Exclusion Criteria

•Symptomatic brain metastases at the time of initiation of systemic therapy.
•Other systemic therapy within 14 days of initiation of study drug.
•Use of corticosteroids to control CNS symptoms. Low-dose steroid use (≤10 mg of prednisone or equivalent) is allowed.
•Presence of leptomeningeal disease.
•Presence of active autoimmune disease. Autoimmune thyroid disease will be allowed if thyroid function is within normal range.
•Overall Exclusion Criteria:
•Symptomatic brain metastases. Any neurologic symptoms present must have resolved with local therapy by the time of administration of study drug.
•Patients with brain metastases for whom complete surgical resection is clinically appropriate.
•Patients with lung cancer with squamous histology.
•Has had prior chemotherapy or targeted small molecule therapy within 2 weeks prior to start of treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Previous radiation to extracranial sites may be completed at any time prior to initiation of pembrolizumab.

Arms & Interventions

Untreated brain metastases from melanoma

pembrolizumab plus bevacizumab

Intervention: Pembrolizumab plus Bevacizumab

Untreated brain metastases from NSCLC

pembrolizumab plus bevacizumab

Intervention: Pembrolizumab plus Bevacizumab

Outcomes

Primary Outcomes

Brain Metastasis Response Rate (BMRR)

Time Frame: up to 2 years from start of treatment

Brain metastasis response rate (BMRR) using modified RECIST (mRECIST) criteria

Secondary Outcomes

Steroid Use(up to 2 years from start of treatment)
Overall Response Rate (ORR)(up to 2 years from start of treatment)
Progression-free Survival (PFS)(up to 9 years from start of treatment or to disease progression)
Safety and Toxicity of Combination Pembrolizumab and Bevacizumab Assessed Using Common Terminology Criteria for Adverse Events v. 4.(up to 2 years from start of treatment)