This pilot study is configured as a non-inferiority comparison of Performance Status 2 patients with Performance Status 0-1 patients, with the goal of demonstrating non-inferiority in terms of efficacy (progression-free survival, overall survival) and safety (rates of adverse events, quality of life) when treating Performance Status 2 patients with the same first-line immunotherapy-based regimen as Performance Status 0-1 patients.
Patients must have a cytological or histological diagnosis of non-small cell lung cancer that is metastatic or unresectable for which standard curative measures do not exist.
No prior systemic treatment with either chemotherapy or immunotherapy for non-curative intent. Patients may have previously received cancer treatment with curative intent for prior early-stage disease.
At least 18 years old.
ECOG performance status of 0-2, as determined by the treating physician in the consult note.
Nonsmall cell lung cancer that is known at registration to be positive for a tumor activating alteration for which first line targeted therapy is indicated9; specifically, a targetable mutation in epidermal growth factor receptor (EGFR), gene rearrangement of anaplastic lymphoma kinase (ALK), gene rearrangement of c-ros oncogene 1 (ROS1), or mutation in B isoform of rapidly accelerated fibrosarcoma (B-Raf). For non-squamous subtypes, molecular testing of tumor and peripheral blood should be attempted for actionable biomarkers, but if there is an insufficient quantity of tumor material for testing and it is not feasible to attempt additional biopsies before starting systemic therapy, then these biomarker results are not necessary for inclusion on the study. For squamous subtype, molecular testing should be considered but is not necessary for inclusion on the study.
Known to have an active autoimmune disease that required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, systemic corticosteroids, or immunosuppressive drugs).
History of (non-infectious) pneumonitis that required systemic corticosteroids.
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Parallel
Pembrolizumab
DrugALL PARTICIPANTS: Pembrolizumab 200 mg intravenously (IV) on day 1 of each 3-week cycle for 4 cycles. Participants with predictive biomarker PD-L1 greater than or equal to 50% will not receive any other drugs besides pembrolizumab.
Carboplatin
DrugFOR PARTICIPANTS IN EITHER ARM with non-squamous OR squamous subtype, predictive biomarker PD-L1 less than 50%: Carboplatin area under the curve (AUC) 5 IV on day 1 of each 3-week cycle for 4 cycles.
Paclitaxel
DrugFOR PARTICIPANTS IN EITHER ARM with squamous subtype, predictive biomarker PD-L1 less than 50%: Paclitaxel 200 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles.
Nab paclitaxel
DrugFOR PARTICIPANTS IN EITHER ARM with squamous subtype, predictive biomarker PD-L1 less than 50%: Nab-paclitaxel 100 mg/m2 on day 1, 8, 15 of 3-week cycle for 4 cycles.
Quality of Life Questionnaire, lung cancer-specific (QLQ-LC13)
Other interventionThe QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items.
QLQ-C30 Global Health/Quality of Life Questionnaire
Other intervention30 item questionnaire - Functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, and nausea and vomiting), global health status and quality of life scale, also several single-item symptom measures
COPD Assessment Test and modified Medical Research Council Dyspnea Patient Reported Outcomes
Other interventionDyspnea scale scores in patients with respiratory disease (particularly COPD) to establish baseline functional dyspnea burden (taken pre-study at Week 0 and Post Treatment at week 13)
Pemetrexed
DrugFOR PARTICIPANTS IN EITHER ARM with nonsquamous subtype, predictive biomarker PD-L1 less than 50%: Pemetrexed 500 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles.
Proportion of Participants with Progression-Free Survival
Using non-blinded central imaging using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 to define progressive disease. RECIST v 1.1 criteria: * Complete Response (CR): Disappearance of all target lesions. * Partial Response (PR): Decrease by ≥ 30% in sum of longest diameter of target lesions. * Stable Disease (SD): Not meeting criteria for CR, PR, or PD. * Progressive Disease (PD): Increase by ≥ 20% in sum of longest diameter of target lesions or the appearance of one or more new lesions. Participants that did not have radiographically measurable metastatic disease by RECIST criteria before starting treatment, progression is defined as the development of new lesions or by unequivocal progression of existing non-target lesions.
Incidences of Grade 3 to Grade 5 Treatment-Related Adverse Events
Adverse events will be defined using CTCAE Version 5.0 after four cycles (12 weeks).
Change in Overall Quality of Life/Global Health Status - EORTC QLQ-C30
Using the total score of the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), a 30-item questionnaire for functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, and nausea and vomiting), global health status and quality of life scale, also several single-item symptom measures. Scoring scale : 1 (Not at all) to 4 (Very much), 1 (Very poor) to 7 (Excellent). Minimum score 0, maximum score 100. For functional and global quality of life scales, higher scores mean a better level of functioning. For symptom-oriented scales, a higher score means more severe symptoms.
Proportion of Participants with Deterioration in Symptoms - QLQ-LC13
Patient reported deterioration in three symptoms: Cough, chest pain, or dyspnea as measured by the symptoms scales as part of the Quality of Life Questionnaire Lung Cancer Module (QLQ-LC13). Deterioration is defined as a 10-point or greater decrease from baseline in either cough, chest pain, or dyspnea and subsequently confirmed by a second adjacent 10-point or greater decrease from baseline in the same symptom)
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Wake Forest University Health Sciences
Lead sponsor
National Cancer Institute (NCI)
Collaborator
