586P - Clinical validation of a multiplex polymerase chain reaction (mPCR) assay to identify patients (pts) with NSCLC suitable for mobocertinib treatment

Background

Mobocertinib is the first oral tyrosine kinase inhibitor approved to treat epidermal growth factor receptor (EGFR) exon 20 insertion mutation positive (ex20ins+) NSCLC. Traditional PCR detects a limited number of EGFR ex20ins variants, identifying ≤50% of pts with EGFR ex20ins. The AmoyDx Pan Lung Cancer PCR panel is a real-time mPCR assay for qualitative detection of alterations in 11 driver genes, including EGFR. Here we assess methods to detect EGFR ex20ins, compare mobocertinib efficacy in pts tested for EGFR ex20ins using these methods, and analyze EGFR ex20ins detection coverage using real-world datasets.

Methods

Pts were enrolled in the mobocertinib phase 1/2 study (NCT02716116) based on EGFR ex20ins detected by various local tissue or liquid clinical trial assays (CTAs). In this analysis, baseline tissue samples were evaluated for EGFR ex20ins status using AmoyDx mPCR. Pt samples from the phase 1/2 trial (n=57) and those from commercially acquired with NSCLC (n=10) were used to determine concordance between mPCR and CTAs. Efficacy analyses were performed in platinum-pretreated pts (PPP; N=114 [FDA-approved population]) with EGFR ex20ins+ NSCLC) from the trial. Retrospective analysis was conducted in pts with NSCLC who had confirmed EGFR ex20ins using 1 global clinical trial and 4 real-world data sources.

Results

We found concordance between mPCR assessment and CTAs in samples from the CTA EGFR ex20ins-positive (n=52) and CTA EGFR ex20ins-negative populations (n=10) tested by mPCR. Point estimates of positive and negative percentage agreement (95% confidence interval) were 91.2% (80.7%–97.1%) and 100% (69.2%–100%), respectively. Response-evaluable pts who tested EGFR ex20ins+ by mPCR (n=50) had a confirmed objective response rate of 28.0% and a disease control rate of 80.0% on mobocertinib. In the retrospective analysis, mPCR identified EGFR ex20ins in an estimated 79.0% (502/636) of pts.

Conclusions

The AmoyDx mPCR assay performed better than traditional PCR and effectively identified pts with EGFR ex20ins+ NSCLC who may benefit from mobocertinib therapy, providing a fast and effective diagnostic option to guide treatment.

Clinical trial identification

NCT02716116, 3/23/2016.

Editorial acknowledgement

Professional medical writing assistance was provided by Corey Burgin, PhD, of Peloton Advantage, LLC, an OPEN Health company.

Legal entity responsible for the study

Takeda Development Center Americas, Inc.

Funding

This study was funded by Takeda Development Center Americas, Inc., Lexington, MA, USA.

Disclosure

C. Zhou: Financial Interests, Personal, Other, Lecturing: Eli Lilly China, Sanofi, Roche, Merck Sharp & Dohme, Qilu, Hengrui, Innovent Biologics, Luye Pharma, TopAlliance Biosciences Inc, Amoy Diagnostics, CStone Pharmaceuticals. V. Bunn, M. Lin, J. Huang, J. Wang, R.J. Fram, S. Vincent, Y. Li: Financial Interests, Personal, Full or part-time Employment: Takeda. All other authors have declared no conflicts of interest.