The following article features coverage from the IASLC 2019 World Conference on Lung Cancer meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

First results from the National Lung Matrix Trial (NLMT), the largest global precision medicine trial in non-small cell lung cancer (NSCLC), showed that the probability of success with respect to achieving a clinically relevant objective response rate (ORR) in patients treated with crizotinib was very high for those with disease characterized by ROS1 gene fusions and a MET exon 14-skipping mutation — but the response was not as evident in those with NSCLC characterized by a MET amplification. The findings of this analysis were reported at the IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer in Barcelona, Spain.

The NLMT (ClinicalTrials.gov Identifier: NCT02664935) is a multidrug, phase 2 study of adaptive design consisting of multiple single arms, each evaluating targeted therapy in a cohort of adult patients with NSCLC characterized by the presence of 1 or more specific actionable molecular alteration(s) as detected by a specific targeted sequencing panel.  

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With an estimated final enrollment of 620 participants, 315 patients have been enrolled in NLMT from a screening population of more than 4000.

Median progression-free survival (PFS) greater than 3 months, an ORR of greater than 30%, or a durable clinical benefit rate (DCB) of greater than 30% as assessed at 24 weeks are considered to be clinical outcomes that warrant continuation of studies of single agents. Within NMLT, 19 cohorts are currently recruiting patients.

Of the 6 cohorts of patients treated with the CDK4/6 inhibitor, palbociclib, the median PFS in patients with disease characterized by a KRAS mutation (30 individuals) was reported to be 5.8 months.

Interim efficacy analyses conducted in other study cohorts, such as patients with disease characterized by an NF1 mutation receiving the MEK inhibitor selumetinib, in combination with docetaxel (16 individuals); and the cohort of patients with NSCLC characterized by the double LKB1/KRAS mutation who were treated with the mTOR inhibitor, vistusertib (23 individuals); met the criteria for study continuation.

However, the arm of the study evaluating vistusertib in the cohort of patients with disease characterized by a single mutation in LKB1 was closed following an interim analysis of efficacy.

The study authors noted that “these first results from the largest stratified medicine data set in NSCLC indicate further molecular stratifications could benefit from targeted therapies. Reporting interim outputs for all cohorts will allow reappraisal of the global stratified medicine strategy in cancer.”

Read more of Cancer Therapy Advisor‘s coverage of the IASLC annual meeting by visiting the conference page.

Reference

Middleton GW, Popat S, Fletcher P, et al. National Lung Matrix Trial (NLMT): First results from an umbrella phase II trial in advanced non-small cell lung cancer (NSCLC). Presented at: IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract PL02.09.