Primary Objective(s), Hypothesis(es), and Endpoint(s)~I. Objective: To evaluate the efficacy of single agent chemotherapy and pembrolizumab in elderly (≥ 75 years) advanced NSCLC patients Hypothesis: We propose that single agent chemotherapy with pembrolizumab will be better tolerated and will provide similar efficacy as platinum-based combination chemotherapy with pembrolizumab in advanced elderly (≥75 years) NSCLC patients.~Primary Endpoint:~I. Assess median PFS in elderly (≥ 75 years) advanced NSCLC patients with tumor PD-L1 (<50%) treated with pemetrexed or nab-paclitaxel and pembrolizumab.~Secondary Objective(s), Hypothesis(es), and Endpoint(s)~I. Objective: To assess additional measure of efficacy of the regimen. To define the toxicity of the regimen in addition~II. Hypothesis: In this patient population single agent chemotherapy and pembrolizumab will provide similar efficacy but improved tolerability as 2 drug combination with pembrolizumab.~Secondary Endpoints:~I. Assess overall survival in the study population II. Assess the toxicities with the study therapy and the rate of discontinuation of study therapy due to toxicities related to study therapy~Exploratory Objective:~I. Objective: To define correlatives that can identify patients most likely to benefit from the study therapy.~II. Correlate PFS with blood-based tumor mutational burden and ctDNA.~Participants who experience confirmed disease progression or start a new anticancer therapy, will move into the Survival Follow-Up Phase and should be contacted by telephone every 12 weeks to assess for survival status until death, withdrawal of consent, or the end of the trial, whichever occurs first.
This Phase II trial is to see how well single agent chemotherapy and pembrolizumab work elderly patients (≥ 75 years) with advanced non small cell lung cancer (NSCLC). Pembrolizumab stimulates your immune system to help fight lung cancer. This treatment approach may be better tolerated in elderly patients.