This is a prospective, randomized, single-site, open-label Phase II trial of neoadjuvant pembrolizumab (3 cycles) followed by surgery, versus concomitant neoadjuvant pembrolizumab with platinum doublet chemotherapy (3 cycles) followed by surgery for participants with Stage IA3, IB and IIA non-small-cell lung cancer (NSCLC). Participants will be offered pembrolizumab (6 cycles), and standard of care adjuvant chemotherapy (4 cycles) if applicable.
The use of ctDNA levels and resolution in relation to treatment response has been studied in various types of cancer, notably melanoma, colorectal and pancreatic cancers. In pancreatic cancer, it was particularly noted to be useful for the prediction of recurrence and survival patterns. In NSCLC, there is a growing need to identify patients who are more likely to respond to immunotherapies given the rates of recurrence, and ctDNA was described to be a useful tool in the prediction of pathological response in this population. In fact, ctDNA was shown to correlate with disease resolution in NSCLC and higher levels of ctDNA in non-responding patients. The central research question of this trial is focused on the ability to predict the occurrence of a pCR based on resolution of ctDNA detectability in early stage NSCLC. The biomarker collection plan will provide tumor and plasma samples from which whole exome sequencing will be performed to monitor disease response. The endpoint is focused on the elimination of ctDNA (both replicates = 0%) at the completion of systemic therapy, prior to surgical resection. All patients will be re-tested for ctDNA levels 30 days post-surgery to determine if those patients who did not experience ctDNA resolution after systemic therapy will experience resolution with the addition of surgery. With the ctDNA treatment response arc, the investigators will be able to address the primary objective of the study: to establish ctDNA levels in early stage NSCLC as a reliable measure of local disease burden in the context of systemic therapy, with the lower end of the detection limit correlating to the extent of pathological response. The investigators hypothesize that in a cohort of patients with stage IA3, IB and IIA NSCLC, pre-operative pembrolizumab with or without histology-specific chemotherapy will cause resolution of ctDNA detectability that correlates with a pathological complete response (pCR) to therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
44
Neoadjuvant pembrolizumab 200 mg IV every 3 weeks, given on cycle day 1. Adjuvant pembrolizumab 400 mg IV every 6 weeks, given on cycle day 1.
Carboplatin AUC 6 IV (maximum dose: 900 mg) for squamous cell carcinoma, and AUC 5 IV (maximum dose: 750 mg) for non-squamous cell carcinoma, every 3 weeks, given on cycle day 1.
Paclitaxel 200 mg/m2 IV every 3 weeks, given on cycle day 1. Only given to participants with squamous cell carcinoma.
Pemetrexed 500 mg/m2 every 3 weeks, given on cycle day 1. Only given to participants with non-squamous cell carcinoma.
McGill University Health Center
Montreal, Quebec, Canada
RECRUITINGctDNA resolution
ctDNA resolution is defined as the change or resolution in tumor-derived DNA found in the bloodstream from diagnosis to after neoadjuvant therapy and after surgery, correlated with pathological complete response (pCR).
Time frame: Up to 2 years
Imaging measures of response
Imaging measures of response is defined as individual measures of response for conventional CT (quantification of response by RECIST 1.1 criteria), PET (change in standardized uptake values \[SUV\]) and diffusion-weighted MRI (change in apparent diffusion coefficient \[ADC\] obtained by image analysis software package), in correlation with pathological complete response (pCR).
Time frame: Up to 3 years
Pathological complete response (pCR) rate
pCR rate is defined as the percentage of participants having an absence of residual invasive cancer in resected lung specimens and lymph nodes following completion of neoadjuvant therapy.
Time frame: Up to 3 years
Major pathological response (MPR) rate
MPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes following completion of neoadjuvant therapy.
Time frame: Up to 3 years
Adverse event (AE) rate
Number of participants experiencing AEs will be recorded. An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time frame: Up to 3 years
Perioperative complications rate
Number of participants experiencing perioperative complications will be recorded.
Time frame: Up to 3 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.