Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients will receive 200mg pembrolizumab on Day 1 of each 3 week cycle, for 2 cycles, prior to surgery. Pembrolizumab will be administered via IV infusion for 30 minutes. Surgery will occur no later than 6 weeks following the last dose of pembrolizumab.

Patients will receive 200mg pembrolizumab on Day 1 of each 3 week cycle, for 2 cycles. Pembrolizumab will be administered via IV infusion for 30 minutes.Within the week (7 days +/- 3 days) following administration of the second cycle, a single 12 Gy dose of stereotactic radiation therapy (SRT) will be delivered to 50% of the primary tumor only. Definitive surgical resection will occur no later than 6 weeks following the last dose of pembrolizumab.

All study participants will receive pembrolizumab every 3 weeks, for 2 cycles.

Patients in Cohort 2 of the Safety run-in and patients in the expansion cohort who are randomized to the 'pembrolizumab +radiation arm' will receive one dose of SRT within 1 week (+/- 3 days) following the second administration of pembrolizumab.

stereotactic radiation therapy (SRT)

Standard of care surgery to remove cancer

Surgery (Non-interventional, standard of care)

Sue Yom, MD

This is a randomized single-institution, phase II, open-label clinical trial of neoadjuvant pembrolizumab with or without low-dose stereotactic radiation therapy (SRT) in stage I-IIIA non-small lung cancer (NSCLC) patients who are planned to undergo surgical resection of their lung cancer.

Two consecutive run-in cohorts will administer pembrolizumab or pembrolizumab with SRT of 12 Gy to the lateral aspect of the primary tumor. Patients will receive pembrolizumab for 2 cycles prior to surgery or SRT and surgery. Surgical resection of all involved areas of tumor will occur within 6 weeks of the last administration of pembrolizumab. It should be noted that surgery is expected to occur within a much shorter window and 6 weeks would represent the greatest allowable amount of delay.

If during the run-in, only the pembrolizumab-alone cohort meets pre-specified safety parameters, subsequently enrolled patients will enter a larger expansion cohort, with treatment given according to that cohort only. If during the run-in both cohorts meet pre-specified safety parameters, subsequently enrolled patients will enter the expansion cohort and be randomized between preoperative pembrolizumab versus pembrolizumab with SRT of 12 Gy.

Pembrolizumab With and Without Radiotherapy for Non-Small Cell Lung Cancer

PembroX: Enhancing the Immunogenicity of Non-Small Cell Lung Cancer With Pembrolizumab +/- Stereotactic Radiotherapy Delivered in the Preoperative Window, A Randomized Phase II Study With Correlative Biomarkers

The primary endpoint for this study is the change in number of infiltrating CD3+ T cells/ μm2 in the lung cancer tissue from before and after pembrolizumab +/- SRT, based on quantification using immunohistochemistry (IHC) and image analysis.

Proportion of patients achieving a two-fold increase from baseline. The goal of achieving a two-fold increase in 40 percent (%) of the evaluable population is a reasonable one, as estimated from a previous study showing greater-than-three-fold increase in 57% of patients when CD3+ T cells/um2 were measured in prostate cancer tissue treated with a cell- based cancer immunotherapy

Adverse events with an attribution of possible, probable, or definite according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 4 including immune-related AEs will be considered treatment related

Participant safety is defined as \<= 33 percent (%) grade 3 immune-related adverse events according to the CTCAE v. 4

Defined as the time from treatment initiation until death. Participants alive at the end of 12 months will be censored.

Defined as the time from treatment initiation until disease progression. Participants who have not progressed at the end of 12 months will be censored.

The rate of distant metastases at 12 months will be reported

The rate of progression to unresectability following the preoperative program will be reported

Spots Global Cancer Trial Database for non small cell lung cancer, resectable