Tepotinib Plus Osimertinib May Provide Chemo-Free Option for NSCLC After First-Line Osimertinib

Tepotinib plus osimertinib has demonstrated efficacy in advanced, EGFR-mutant, MET-amplified NSCLC that progressed on first-line osimertinib.

Combination treatment with tepotinib and osimertinib has demonstrated efficacy in a phase 2 trial of patients with advanced, EGFR-mutant, MET-amplified non-small cell lung cancer (NSCLC) whose disease progressed on first-line treatment with osimertinib.

Tepotinib plus osimertinib may provide a chemotherapy-free treatment option for this patient population, said Tae Min Kim, MD, PhD, of Seoul National University in the Republic of Korea.

Dr Kim presented these findings, from the INSIGHT 2 study (ClinicalTrials.gov Identifier: NCT03940703), at the 2023 World Conference on Lung Cancer.

INSIGHT 2 enrolled patients with locally advanced or metastatic, EGFR-mutant, MET-amplified NSCLC with acquired resistance to first-line osimertinib. Dr Kim presented results in 128 patients who received tepotinib (500 mg daily) and osimertinib (80 mg daily).

The patients had MET amplification detected by FISH (n=98), liquid biopsy (n=31), or both (n=24). The patients’ median age at baseline was 61 years (range, 20-84), 57.8% were women, 67.2% were never smokers, and 35.2% had brain metastases.  

In the 98 patients who had MET amplification detected by FISH, the objective response rate (ORR) was 50.0%. All 49 responders had a partial response. The median duration of response was 8.5 months. The median progression-free survival (PFS) was 5.6 months, and the median overall survival (OS) was 17.8 months.

In the 31 patients who had MET amplification detected by liquid biopsy, the ORR was 54.8%. The median duration of response was 5.7 months. The median PFS was 5.5 months, and the median OS was 13.7 months.

In the 24 evaluable patients with brain metastasis who had MET amplification detected by FISH, the intracranial ORR was 29.2%. There were 6 complete responses and 1 partial response. The duration of intracranial response was not reached, and the median intracranial PFS was 7.8 months.

The rate of treatment-related adverse events (TRAEs) was 88.3%, and the rate of grade 3 or higher TRAEs was 34.4%. The most common TRAEs were diarrhea (49.2%), peripheral edema (40.6%), paronychia (22.7%), and nausea (21.1%). The most common grade 3 or higher TRAEs were peripheral edema (4.7%) and decreased appetite (3.9%).

TRAEs led to treatment discontinuation in 10.2% of patients. Four patients had fatal TRAEs that were considered potentially related to either study drug.

Based on these results, Dr Kim concluded that tepotinib plus osimertinib had a “manageable safety profile” and “demonstrated robust and durable efficacy” in this trial.

Disclosures: This research was supported by EMD Serono Research & Development Institute, Inc. in collaboration with Merck KGaA. No other disclosures were provided, but some study authors are employed by Merck.

This article originally appeared on Cancer Therapy Advisor


Kim TM, Guarneri V, Jye VP, et al. Tepotinib + osimertinib in EGFR-mutant NSCLC with MET amplification following 1L osimertinib: INSIGHT 2 primary analysis. Presented at WCLC 2023. September 9-12, 2023. Abstract OA21.05.