Genetic Predictors of Benefit to Pembrolizumab

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title: Identifying Genetic Predictors of Durable Clinical Benefit to Pembrolizumab in Advanced Non-small Cell Lung Cancer (NSCLC) Alone and in Combination With Chemotherapy.

Status Terminated

Clinical Trial Summary

The primary objective is to determine if mutation load underlies sensitivity to pembrolizumab alone and in combination with chemotherapy. This will be a 3-arm, multi-center, open-label, non-randomized biomarker trial in patients with advanced, treatment-naive NSCLC. Patients will receive 1 of 3 possible cohorts as per investigator's discretion. Patients with non-squamous histology may receive any of the 3 cohorts; patients with squamous histology may receive either cohorts 1 and 2.

Clinical Trial Description

Somatic mutations leading to cancer are related to endogenous or exogenous DNA damaging processes. The resultant mutations can be separated into two categories - (i) mutations that provide selective advantage for clonal expansion and (ii) mutations that do not result in growth advantage. The latter have been termed passenger mutations, while the former are referred to as driver mutations. It is widely believed that the number of driver mutations in a cancer sample is limited to a handful, usually two or more but less than ten. In contrast, the genome of a cancer can harbor more than a million somatic mutations most of which are considered to be passengers.

Several studies have shown that the passenger mutations may not be oncogenic drivers but may be of importance in adaptive immune resistance of a tumor. In particular the relevant mutations are likely to be the nonsynonymous exonic mutations in tumors; these may give rise to novel proteins that differ from their wild type counterparts and are immunogenically more relevant. The study will explore if there is a relationship between the genetic mutations and the success of pembrolizumab. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung

• NCT number: NCT02710396
• Study type: Interventional
• Source: Columbia University
• Status: Terminated
• Phase: Phase 2
• Start date: May 31, 2016
• Completion date: March 10, 2021