NCT04638582

Pembrolizumab as Neoadjuvant Therapy for Resectable Stage IA3 to IIA Non-Small Cell Lung Cancer (NSCLC)

Phase II Randomized Controlled Trial of Neoadjuvant Pembrolizumab or Pembrolizumab With Histology-Specific Chemotherapy for Operable Stage IA3 to IIA Non-Small Cell Lung Cancer (NSCLC)

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

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.

Conditions

• Lung Cancer, Nonsmall Cell

Interventions

Type	Name	Description
DRUG	Pembrolizumab	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.
DRUG	Carboplatin	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.
DRUG	Paclitaxel	Paclitaxel 200 mg/m2 IV every 3 weeks, given on cycle day 1. Only given to participants with squamous cell carcinoma.
DRUG	Pemetrexed	Pemetrexed 500 mg/m2 every 3 weeks, given on cycle day 1. Only given to participants with non-squamous cell carcinoma.

Timeline

• Start date: 2022-08-28
• Primary completion: 2026-04-14
• Completion: 2026-04-14
• First posted: 2020-11-20
• Last updated: 2026-04-17

Locations

1 site across 1 country: Canada