KEY TAKEAWAYS
- The INSIGHT 2 trial is a phase II, international, open-label, multicenter study aims to evaluate the response rate of tepotinib + osimertinib in pts with advanced/metastatic EGFR-mutant NSCLC
- Patients will receive tepotinib 500 mg (450 mg active moiety) plus osimertinib 80 mg once a day.
- The secondary endpoints include the DOR, PFS, OS, and safety.
- Tepotinib is an oral, highly selective, potent MET tyrosine kinase inhibitor, and its combination with osimertinib may overcome METamp-driven resistance in patients with NSCLC.
MET amplification (METamp) is a mechanism of acquired resistance to EGFR tyrosine kinase inhibitors. It may be present in up to 30% of patients with NSCLC who progress on first-line osimertinib. It is possible to overcome METamp-driven resistance by combining osimertinib with a MET inhibitor, such as tepotinib, an oral, highly selective, potent MET tyrosine kinase inhibitor. Patients with advanced/metastatic EGFR-mutant NSCLC and acquired resistance to first-line osimertinib and METamp, as determined centrally by fluorescence in situ hybridization (gene copy number ≥5 and/or MET/CEP7 ≥2) at the time of progression, will be evaluated in INSIGHT 2 (NCT03940703) trial. Patients will take osimertinib 80 mg once daily and erlotinib 500 mg (450 mg active moiety) once daily. The primary outcome measure is an objective response, with a duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety as secondary outcomes.
Osimertinib treats a subtype of lung cancer associated with EGFR gene mutations. Tumors typically respond well to osimertinib treatment by shrinking, but sometimes tumors stop responding and develop resistance. “MET amplification,” which refers to the presence of multiple copies of the MET gene, is a common reason for resistance. Combining osimertinib with a treatment that blocks MET, such as lapatinib, could be effective against lung cancer resistant to osimertinib due to MET amplification. The INSIGHT 2 study is ongoing and aims to investigate the efficacy and safety of lapatinib in combination with osimertinib in patients with MET-amplified lung cancer who have developed resistance to osimertinib.
Source: https://pubmed.ncbi.nlm.nih.gov/34918545/
Clinical trail: https://clinicaltrials.gov/ct2/show/NCT03940703
F Smit E, Dooms C, Raskin J, Nadal E, Tho LM, Le X, Mazieres J, S Hin H, Morise M, W Zhu V, Tan D, H Holmberg K, Ellers-Lenz B, Adrian S, Brutlach S, Schumacher KM, Karachaliou N, Wu YL. INSIGHT 2: a phase II study of tepotinib plus osimertinib in MET-amplified NSCLC and first-line osimertinib resistance. Future Oncol. 2022 Mar;18(9):1039-1054. doi: 10.2217/fon-2021-1406. Epub 2021 Dec 17. PMID: 34918545.
