A Randomized Phase III Trial of Chemo-Immunotherapy vs Immunotherapy Alone for the Vulnerable Older Adult With Advanced Non-Small Cell Lung Cancer: The ACHIEVE Study

Brief Summary

Detailed Description

PRIMARY OBJECTIVE: I. To evaluate whether there is an improvement in overall survival (OS) with chemotherapy combined with pembrolizumab compared to single agent pembrolizumab in this vulnerable older adult patient population. SECONDARY OBJECTIVES: I. To evaluate any difference in progression free survival (PFS) with chemotherapy combined with pembrolizumab as compared to single agent pembrolizumab. II. To evaluate the difference in PFS rate at 3 months and at 6 months with chemotherapy combined with pembrolizumab as compared to single agent pembrolizumab. III. To evaluate the difference in best objective response rate using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria to assess whether chemotherapy combined with pembrolizumab results in improved response rates compared to treatment with single agent pembrolizumab. IV. To evaluate toxicity in those treated with chemotherapy combined with pembrolizumab compared to those treated with single agent pembrolizumab. V. To evaluate patient reported quality of life (QOL) evaluations between treatment arms. EXPLORATORY OBJECTIVES: I. To compare safety and tolerability between treatment arms. II. To explore factors within the pre-treatment geriatric assessment (GA) as predictors of toxicity and outcomes. To describe changes between the intended chemotherapy treatment planned versus treatment given and referrals placed by treating provider based on GA results. III. To evaluate the assessment of a novel, composite fPFS score using disease progression/functional impairment assessment as a potential correlate to OS in this vulnerable population. IV. To evaluate the correlation of 3-months PFS with OS as a potential surrogate of OS benefit. V. To evaluate the correlation of 6-months PFS with OS as a potential surrogate of OS benefit. VI. To assess elective dose intensity of chemotherapy of patients who receive doublet chemotherapy versus single agent chemotherapy. EXPLORATORY CORRELATIVE OBJECTIVE: I. To relate gut microbe abundances to treatment outcomes, toxicity, and geriatric assessments. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: INDUCTION: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for 2 years in the absence of disease progression or unacceptable toxicity. ARM B: INDUCTION: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Patients also receive investigator's choice of a chemotherapy regimen: 1) Pemetrexed IV over 10 minutes + carboplatin IV over 30-60 minutes on day 1 of each cycle; 2) Nab-paclitaxel IV over 30 on days 1, 8, and 15 of each cycle + carboplatin IV over 30-60 minutes on day 1 of each cycle; 3) Paclitaxel IV over 1 hour on day 1, 8, and 15 of each cycle or over 3 hours on day 1 of each cycle + carboplatin IV over 30-60 minutes on day 1 of each cycle; 4) Nab-paclitaxel IV over 30 minutes on days 1, 8 and 15 of each cycle; 5) Paclitaxel IV over 3 hours on day 1 of each cycle or over 1 hour on days 1, 8, and 15 of each cycle; or 6) Pemetrexed IV over 10 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients undergo magnetic resonance imaging (MRI) at baseline and computed tomography (CT) and/or positron emission tomography (PET) on the trial at baseline and throughout the trial. After completion of study treatment, patients are followed up every 3 months if \< 2 years from randomization and every 6 months if 2-5 years from Step 1 registration.

Primary Outcomes

Secondary Outcomes

• Progression free survival (PFS)(From randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause, whichever occurs first, assessed up to 5 years)
• Six month PFS(From randomization to documented disease progression per RECIST 1.1 or death from any cause, whichever occurs first, assessed at 6 months)
• Best objective response(Up to 5 years)
• Incidence of adverse events(Up to 2 years)
• Evaluation of quality of life (QOL) measures(Baseline up to 6 months)