Tagrisso (osimertinib)

P2, N=173, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2026 --> Apr 2027 | Trial primary completion date: Apr 2026 --> Apr 2027

Taxane‑based chemotherapy was associated with more favorable outcomes than pemetrexed in dramatic progression after osimertinib resistance, with higher non‑hematologic toxicity. These findings, supported by exploratory in vitro sensitivity, warrant prospective validation.

EGFR tyrosine kinase inhibitors, including osimertinib, generally exhibit lower efficacy in patients with the L858R-mutant NSCLC compared with those with exon 19 deletion (del19). Grade more than or equal to 3 adverse events occurred in 42% of patients. In real-world settings, RAM plus ERL demonstrated favorable efficacy in patients with L858R-mutant NSCLC and manageable toxicity.

RBM10 mutation is frequent in Japanese patients with NSCLC with EGFR mutation, especially those with L858R or uncommon mutations, and was associated with late-onset and features of indolent tumor growth.

P2/3, N=854, Recruiting, AbbVie | Trial completion date: Nov 2036 --> Dec 2031 | Trial primary completion date: Nov 2036 --> Dec 2031

P2, N=30, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Mar 2027 --> Mar 2028 | Trial primary completion date: Feb 2026 --> Feb 2027

After about 20 years of exciting improvements in treatment efficacy outcomes of advanced epidermal growth factor receptor (EGFR) mutant and anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC), also combined with a progressively better safety profile, from chemotherapy to new generation tyrosine kinase inhibitors (TKIs) (osimertinib, alectinib, brigatinib), the recent MARIPOSA and CROWN trials have changed this trend. The story would be easy and totally positive if these two innovative, amazing treatments were not associated with new peculiar features in safety profiles that must be discussed with patients, because they potentially affect their quality of life. When treating these patient populations, the peculiar safety profiles of amivantamab plu lazertinib and lorlatinib require a well-structured shared decision making, "where and when", both the high probability of a longer survival and the risk of worse quality of life must be well announced and explained to our patients before the shared final treatment choice.

A number of BM treatment-effective drugs have shown BM-preventive effects: In NSCLC, the EGFR-inhibitor osimertinib and ALK inhibitors like alectinib, brigatinib and lorlatinib lower the incidence of BM. In HER2-positive breast cancer, tucatinib and trastuzumab deruxtecan have preventive activity in patients without BM at baseline...Preventing BM requires a personalized, multidisciplinary approach, integrating tumor biology, individual risk assessment, and therapeutic advances. Secondary prevention in patients with BM is as vital as tertiary prevention, warranting prospective validation of preclinical concepts.

Inhibition of downstream signaling and cell proliferation by vabametkib plus lazertinib were evaluated in osimertinib-resistance NSCLC cell lines (HCC827-AR) and patient-derived organoid (YUO-010) by western blot and Cell Titer-Glo assay. Consistent with the in vitro findings, treatment with vabametkib plus lazertinib produced pronounced suppression of tumor growth in both models through a synergistic mechanism. These findings establish vabametkib plus lazertinib as a promising strategy for MET-amplified NSCLC, currently under evaluation in an ongoing phase II clinical trial (NCT05541822).

P1/2, N=434, Recruiting, Vivace Therapeutics, Inc | Trial completion date: Jun 2027 --> Mar 2030 | Trial primary completion date: Dec 2026 --> Nov 2029

P2, N=80, Not yet recruiting, Yonsei University

P1/2, N=22, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027