2023 North America Conference on Lung Cancer (NACLC) - Posters and Abstracts-PP01.84 (Poster) Tepotinib + osimertinib in EGFR mutant NSCLC with MET amplification following 1L osimertinib: INSIGHT 2 primary analysis

PP01.84 (Poster) Tepotinib + osimertinib in EGFR mutant NSCLC with MET amplification following 1L osimertinib: INSIGHT 2 primary analysis

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The primary analysis of the Phase II INSIGHT 2 study evaluated the efficacy and safety of tepotinib in combination with osimertinib in patients with EGFR-mutant non-small cell lung cancer (NSCLC) and MET amplification (METamp) following progression on first-line osimertinib. The study included 128 patients, and the primary endpoint was objective response rate (ORR).<br /><br />In patients with centrally detected METamp confirmed by tumor biopsy fluorescence in situ hybridization (FISH), the ORR was 50.0% and consistent across all patient subgroups. The median duration of response (mDOR) was 8.5 months, median progression-free survival (mPFS) was 5.6 months, and median overall survival (mOS) was 17.8 months.<br /><br />In patients with METamp detected by liquid biopsy next-generation sequencing (NGS), the ORR was 54.8%, mDOR was 5.7 months, mPFS was 5.5 months, and mOS was 13.7 months.<br /><br />Tepotinib monotherapy demonstrated an ORR of 8.3%, as previously reported.<br /><br />The study also found that outcomes were better when there were no co-occurring mechanisms of osimertinib resistance. The combination therapy was associated with a manageable safety profile, and health-related quality of life was maintained.<br /><br />The efficacy outcomes in Asian patients were also assessed separately. Among Asian patients with centrally detected METamp, the ORR was 59.6%. The mDOR was 7.3 months, mPFS was 6.9 months, and mOS was 19.8 months.<br /><br />The most common treatment-related adverse events were diarrhea and peripheral edema. A dose reduction was necessary in 20.3% of patients due to adverse events, and 10.2% discontinued treatment due to adverse events.<br /><br />The study concludes that tepotinib in combination with osimertinib provides a potential chemotherapy-sparing oral targeted treatment option for patients with EGFR-mutant NSCLC and METamp after progression on first-line osimertinib, who have a high unmet need. Further research is warranted to confirm these findings and explore the potential benefits in different patient populations.

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Richard O'Hara

Keywords

INSIGHT 2 study

tepotinib

osimertinib

EGFR-mutant NSCLC

MET amplification

ORR

mDOR

mPFS

mOS

adverse events