Anti PD-1 Neo-adjuvant Treatment for NSCLC — MK3475-223  

Non Small Cell Lung Carcinoma Clinical Trial

Official title: Anti PD-1 Neo-adjuvant Treatment for Early Stage NSCLC - Phase I Study

Status Completed

Clinical Trial Summary

A single arm, phase I, dose escalation trial and expansion cohort, examining the safety and feasibility of neoadjuvant pembrolizumab treatment for early resectable NSCLC patients.

Hypothesis: The investigators hypothesize that response rate to neo-adjuvant pembrolizumab will be higher than the response rate of advanced NSCLC patients.

Clinical Trial Description

16-28 patients with apparently operable NSCLC, clinically staged I-II with a resectable tumor would be recruited. Recruitment would be based on clinical assessment by a qualified Thoracic surgeon, with the appreciation that some of the recruited patients would eventually be deemed to be non-operable, or with a non-resectable disease, or to harbor a diagnosis different from NSCLC.

Screen of consenting patients would include a diagnostic biopsy that includes core needle biopsy procedure. Fresh as well as formalin fixed paraffin embedded baseline tumor samples will be obtained according to common Standard Operating Procedures. Specimens would be processed as per pathology standard of care and two cores or more will be utilized later for the research study.

A patient recruited after a previous diagnostic biopsy, would be eligible for the trial only if willing to undergo a repeat diagnostic procedure as above. Processing of biopsy material will be similar regardless if it is first or second biopsy.

Trial treatment will commence only following pathological confirmation of NSCLC, complete staging including CT-PET and brain imaging, and positive pre-op cardiac and pulmonary assessment.

Study schedule Dose levels of this study are defined by dose of drug as well as number of treatments and required interval from last treatment to surgery. At least 3 subjects in a dose cohort must complete the dose limiting toxicity (DLT) evaluation period before dosing is initiated at the next higher dose level. Only toxicities occurring during the DLT period will be considered as DLTs and utilized to inform dose escalation decisions. The DLT period starts with the first dose of pembrolizumab till 30 days post-surgery.

Cohorts consists of 3-6 subjects per dose level, to be treated with study therapy following a 3+3 schema.

Dose escalation will proceed between cohorts according to a modified "3+3 design," as explained in the following scheme. Dose-limiting toxicity (DLT) is defined below and is confined in time as defined above. As a safety feature, a new dosing/schedule level will open only after the end of 30 post-operative days of the last patient in the previous cohort. If cohort one will be found to be too high as RP2D/schedule, the next patients will be treated at a dose/schedule level minus one. Only one step of dose reduction is planned. ;

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non Small Cell Lung Carcinoma
• Stage I
• Stage II

• NCT number: NCT02938624
• Study type: Interventional
• Source: Sheba Medical Center
• Status: Completed
• Phase: Phase 1
• Start date: January 7, 2017
• Completion date: August 2021