Phase II Study of Pembrolizumab in Combination With Platinum-based Chemotherapy in Nonsmall Cell Lung Cancer Patients With Targetable Genetic Alterations Previously Treated With Appropriate Targeted Agents With Progressive Disease

University of Michigan Rogel Cancer Center7 sites in 1 country33 target enrollmentOctober 3, 2017

ConditionsNon-small Cell Lung Cancer

InterventionsPembrolizumab Carboplatin Pemetrexed

DrugsPembrolizumab Carboplatin Pemetrexed

Overview

Phase: Phase 2
Intervention: Pembrolizumab
Conditions: Non-small Cell Lung Cancer
Sponsor: University of Michigan Rogel Cancer Center
Enrollment: 33
Locations: 7
Primary Endpoint: The Percentage of Patients That Respond to Treatment
Status: Completed
Last Updated: 11 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Investigators hypothesize that addition of pembrolizumab will enhance the efficacy of carboplatin and pemetrexed in patients with EGFR-mutation-positive NSCLC, or patients with other genetic alterations, and who have disease progression following appropriate targeted therapies.

Registry

clinicaltrials.gov

Start Date

October 3, 2017

End Date

February 20, 2025

Last Updated

11 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Michigan Rogel Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Cohort-specific:
•Cohort 1- EGFR mutation positive NSCLC patients previously treated with appropriate targeted therapy with progressive and measurable disease per RECIST 1.1 criteria tumor.
•Cohort 2- Other genetically altered NSCLC patients previously treated with appropriate targeted therapy with progressive and measurable tumor.
•Tumor tissue for PD-L1 assessment should be available unless PD-L1 assessment results are already available.
•Patients should not have received any systemic chemotherapy for advanced NSCLC. Patients who received 1 cycle of systemic chemotherapy for advanced NSCLC while awaiting the results of tumor molecular analysis and subsequently were switched to appropriate targeted therapy will be eligible. Patients who have received neoadjuvant, adjuvant or as part of concurrent chemotherapy and radiation are eligible if they received the chemotherapy 12 months or more before the start of study therapy.
•ECOG PS 0-1 (Eastern Cooperative Oncology Group Performance Status: an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.)
•Patients should have recovered to ≤ grade 1 from clinically meaningful (example alopecia is not considered clinically meaningful) adverse events related to prior treatments.
•Patients should be willing and able to provide written informed consent for the trial.
•Be ≥ 18 years of age on day of signing informed consent.
•Demonstrate adequate organ function

Exclusion Criteria

•Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. If the half-life of the drug is known then starting therapy 5 half-lives after the end of the last therapy is acceptable.
•Has a diagnosis of immunodeficiency. Patient should not be of any immunosuppressive therapy or steroids \> prednisone 10mg/day or its equivalent on the day of the start of therapy.
•Has a known history of active TB (Bacillus Tuberculosis)
•Hypersensitivity to pembrolizumab, carboplatin or pemetrexed or any of its excipients.
•Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
•Has had targeted small molecule therapy, or palliative radiation therapy within 1 week prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
•Has a known additional malignancy that is progressing or requires active treatment or the treating physician believes will require therapy within 1 year.
•Has symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
•Has active autoimmune disease that has required systemic treatment in the past 2 years
•Has known history of non-infectious pneumonitis that required steroids or has current pneumonitis. Has known history of interstitial lung disease.

Arms & Interventions

Pembrolizumab/Carboplatin/Pemetrexed

Pembrolizumab 200 mg with carboplatin at AUC (area under the curve dosing) 5 and pemetrexed at 500 mg/m2 administered intravenously every 3 weeks

Intervention: Pembrolizumab

Pembrolizumab/Carboplatin/Pemetrexed

Pembrolizumab 200 mg with carboplatin at AUC (area under the curve dosing) 5 and pemetrexed at 500 mg/m2 administered intravenously every 3 weeks

Intervention: Carboplatin

Pembrolizumab/Carboplatin/Pemetrexed

Pembrolizumab 200 mg with carboplatin at AUC (area under the curve dosing) 5 and pemetrexed at 500 mg/m2 administered intravenously every 3 weeks

Intervention: Pemetrexed

Outcomes

Primary Outcomes

The Percentage of Patients That Respond to Treatment

Time Frame: 5.5 years

The primary endpoint is Response Rate (RR) defined as the rate of complete and partial response. Complete Response (CR): Disappearance of all non-target lesions. All lymph nodes must be non-pathological in size (\<10mm short axis). Partial Response (PR): Persistence of one or more non-target lesion(s) but does not qualify for PD. Progressive Disease (PD): Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered progression).