Tagrisso (osimertinib)

P3, N=418, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Jun 2026 --> Jun 2027

P1, N=8, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting | N=30 --> 8

P2, N=19, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jan 2027

Osimertinib plus Dato-DXd demonstrated clinical benefit in patients with EGFR-mutated advanced NSCLC who progressed on first-line osimertinib. AEs in the 6 mg/kg cohort were of higher frequency and severity but could be managed with prophylaxis, careful monitoring and dose reduction. The safety profile was consistent with the known profiles of the individual drugs. Considering the overall benefit-risk profile, 6 mg/kg is suggested as the preferred Dato-DXd starting dose for combining with osimertinib 80 mg.

Osimertinib was started after a median (25th-75th percentiles) time from tumor resection of 2.9 (2.1-4.9) months. The ELBA Study showed an evolving landscape in biomarker-driven and molecular targeted therapies in early-stage NSCLC management towards the integration of mutational testing into clinical practice, with a growing focus on an optimal definition of adjuvant treatment.

The methylation status or expression level of SORD holds promise as a potential biomarker for predicting Osimertinib efficacy, and targeting SORD-related pathways may provide new strategies for overcoming Osimertinib resistance.

Moreover, this axis contributes to acquired resistance to osimertinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI); combined inhibition of USP5 and osimertinib synergistically induces apoptosis and suppresses tumor growth in vitro and in vivo. These findings establish USP5-mediated stabilization of CD73 as a central mechanism underlying glycolytic metabolism and osimertinib resistance in LUAD, highlighting the USP5/CD73 pathway as a promising prognostic indicator and therapeutic target for LUAD treatment.

P1, N=40, Not yet recruiting, TOLREMO therapeutics AG | N=90 --> 40

Concurrent PEM with EGFR-TKI treatment slowed TMB accumulation rate and resistance acquisition in EGFR-mutated NSCLC compared to single EGFR-TKIs in vitro.

LM has been attracting attention, possibly due to the long-term survival achieved by EGFR-tyrosine kinase inhibitors. Additional information is required to clarify the risk of LM.

Optimizing NSCLC therapy with TKIs requires proactive toxicity monitoring and integration of predictive biomarkers and real-world evidence to enhance efficacy and patient safety.

We evaluated the antitumor effect of the combination therapy with osimertinib and either nintedanib (an indirect TGF-β inhibitor) or vactosertib (a specific TGF-β type I receptor kinase inhibitor). In conclusion, combination therapy with osimertinib and TGF-β inhibitors potentiates osimertinib-induced antitumor immunity. These findings highlight a novel therapeutic strategy for EGFR-mutated NSCLC and warrant further clinical investigation.