Cancer Treatment Today

Osimertinib, also known as AZD9291, is a novel EGFR TKI developed by AstraZeneca, the structure and pharmacology of which are distinct from other third-generation EGFR TKIs.14 It shows 200-fold selectivity for T790M/L858R protein over wild-type EGFR and has been classed as a “breakthrough” compound for fast-track development, having demonstrated perfect objective response rate (ORR) in patients with T790M-positive NSCLC who had progressed on a first-generation EGFR TKI. Osimertinib received its first global approval by the US Food and Drug Administration in November 2015 for patients with metastatic EGFR T790M-positive NSCLC who had progressed on prior systemic therapy, including an EGFR TKI.
I found three studies supporting the combination of Tagisso and tepotnib for progressed NSC Lung Cancer.

Wu YL, Guarneri V, Voon PJ, Lim BK, Yang JJ, Wislez M, Huang C, Liam CK, Mazieres J, Tho LM, Hayashi H, Nhung NV, Chia PL, de Marinis F, Raskin J, Zhou Q, Finocchiaro G, Le AT, Wang J, Dooms C, Kato T, Nadal E, Hin HS, Smit EF, Wermke M, Tan D, Morise M, O’Brate A, Adrian S, Pfeiffer BM, Stroh C, Juraeva D, Strotmann R, Goteti K, Berghoff K, Ellers-Lenz B, Karachaliou N,
Le X, Kim TM; INSIGHT 2 investigators. Tepotinib plus osimertinib in patients with EGFR-mutated non-small-cell lung cancer with MET amplification following progression on first-line osimertinib (INSIGHT 2): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2024 Aug;25(8):989-1002. doi: 10.1016/S1470-2045(24)00270-5. Erratum in: Lancet Oncol. 2024 Oct;25(10):e472. doi: 10.1016/S1470-2045(24)00509-6. PMID: 39089305.

X. Le et al, Tepotinib Plus an EGFR Tyrosine Kinase Inhibitor in Patients With EGFR-Mutant MET-Altered NSCLC: A Case Series. Clinical Lung Cancer Volume 26, Issue 4, June 2025, Pages 338-346.e1

DSW Ten et al, Meeting Abstract: 2023 ASCO Annual Meeting I Free access
Lung Cancer—Non-Small Cell Metastatic May 31, 2023

Daniel Shao-Weng Tan et al, Tepotinib + osimertinib for EGFR mutant (EGFRm) NSCLC with MET amplification (METamp) after first-line (1L) osimertinib. Meeting Abstract: 2023 ASCO Annual Meeting I Lung Cancer—Non-Small Cell Metastatic May 31, 2023