Circulating Tumor DNA Monitoring for Treatment Response Prediction and Treatment Reduction after Surgery in Patients with Stage IB, II, and IIIB Non-small Cell Lung Cancer, DNA-PREDICT Trial

PRIMARY OBJECTIVE:

I. To determine the proportion of patients who achieve ctDNA clearance during neoadjuvant treatment phase and pathologic complete response (pCR) at surgery.

SECONDARY OBJECTIVES:

I. To assess association between ctDNA clearance during neoadjuvant treatment phase and pCR at surgery.

II. To assess recurrence-free survival (RFS) and overall survival (OS) in patients with ctDNA clearance and without ctDNA clearance during neoadjuvant treatment phase.

III. To determine ctDNA clearance and recurrence rates during the post-operative period.

IV. To assess RFS and OS in low-risk (patients who have achieved pCR and ctDNA negative post-surgery) and high-risk (patients who do not achieve pCR or patients who have achieved pCR but ctDNA positive post-surgery) group.

EXPLORATORY OBJECTIVES:

I. To explore genomic and clinical factors of archival tumor sample and pre-treatment diagnostic imaging.

II. To identify predictive biomarkers associated with pathologic response and ctDNA clearance.

III. To measure quality of life and patient reported outcomes.

OUTLINE:

NEOADJUVANT THERAPY [NAT] & SURGERY: Patients with non-squamous NSCLC receive cisplatin intravenously (IV) over 120 minutes or carboplatin IV on day 1 of each cycle plus pemetrexed IV over 10 minutes or paclitaxel IV or docetaxel IV over 60 minutes on day 1 of each cycle, per treating physician's choice. Patients with squamous NSCLC receive cisplatin IV over 120 minutes or carboplatin IV on day 1 of each cycle plus paclitaxel IV on day 1 of each cycle, docetaxel IV over 60 minutes on day 1 of each cycle, or gemcitabine IV over 30 minutes on days 1 and 8 of each cycle, per treating physician's choice. In addition, all patients receive immunotherapy with pembrolizumab IV or nivolumab IV on day 1 of each cycle. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery within 6 weeks of completing NAT.

ADJUVANT THERAPY: After surgery, patients who did not achieve pCR and patients who achieved pCR but are ctDNA positive receive treatment as in NAT above + pembrolizumab every 3 or 6 weeks or nivolumab every 3 weeks for 12 months in the absence of disease progression or unacceptable toxicity. After surgery, patients who achieved pCR and are ctDNA negative receive treatment as in NAT above + pembrolizumab every 3 or 6 weeks or nivolumab every 3 weeks for 6 months in the absence of disease progression or unacceptable toxicity.

All patients also undergo positron emission tomography (PET) or computed tomography (CT) of the chest/abdomen/pelvis (plus optional bone scan) and magnetic resonance imaging (MRI) of the brain or CT of the head during screening. Patients also undergo additional CT of the chest/abdomen/pelvis and blood sample collection throughout the trial.

After completion of study treatment, patients are followed every 3 months for 1 year.