Vizimpro (dacomitinib)

P=N/A, N=90, Not yet recruiting, Shanghai Sixth People's Hospital; Shanghai Sixth People's Hospital

FDA-approved drugs like Gefitinib, Erlotinib, Afatinib, Dacomitinib, and Vandetanib validate the therapeutic significance of the quinazoline framework in modulating different cancer pathways. Structure activity relationship (SAR) analyses reveal that adding halogen, methoxy, or heteroaryl groups at specific ring positions enhance kinase affinity and cytotoxic efficacy. Overall, this review highlights recent progress linking synthetic design, molecular docking, and biological response, establishing quinazoline derivatives as promising multitargeted scaffolds for the design of next-generation anticancer agents.

More detailed analyses of the most potent mutations, S303F, E452K, and L798R, showed that they are activating, can co-operate with other ERBB receptors and are sensitive to clinically available second-generation pan-ERBB inhibitors neratinib, afatinib, and dacomitinib. Furthermore, the S303F mutation, together with a previously identified activating ERBB4 mutation, E715K, promoted resistance to third-generation EGFR inhibitor osimertinib in EGFR-mutant lung cancer model in vitro and in vivo. Together, these results are expected to facilitate clinical interpretation of the most recurrent cancer-associated ERBB4 mutations. The findings provide rationale for testing the efficacy of clinically used pan-ERBB inhibitors in patients harboring driver ERBB4 mutations both in the treatment-naïve setting, and upon development of resistance to targeted agents.

P1, N=22, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed

To our knowledge, ARIA is the largest real-world study of dacomitinib's efficacy and safety. Final analysis of this study showed substantial clinical efficacy of dacomitinib and revealed treatment patterns, such as starting dose, in the real world. Safety data were consistent with dacomitinib's known safety profile. These results support first-line dacomitinib use in Asian patients with EGFR mutation-positive advanced NSCLC.

P=N/A, N=180, Recruiting, Pfizer | Trial completion date: Oct 2025 --> Jan 2026 | Trial primary completion date: Oct 2025 --> Jan 2026

This NMA revealed that cases with EGFR-mutated NSCLC may benefit from different first-line treatment regimens according to their clinicopathological characteristics. On the whole, osimertinib plus CT and amivantamab plus lazertinib emerged as the most noticeable treatment modalities for such cases. (PROSPERO ID: CRD42024506995).

The patient was treated sequentially with three generations of EGFR TKIs-gefitinib, osimertinib, and dacomitinib-while continuing immunosuppressive therapy for graft function. To our knowledge, this is the first reported case of an EGFR L747P-mutated lung adenocarcinoma in a renal transplant recipient benefiting from sequential multi-TKI therapy. This case underscores the importance of vigilant cancer surveillance in transplant recipients and suggests that individualized TKI sequencing may offer clinical benefit, although further evidence is required.

P=N/A, N=180, Recruiting, Pfizer | Trial completion date: Mar 2026 --> Oct 2025 | Trial primary completion date: Mar 2026 --> Oct 2025

And dacomitinib, regorafenib, fruquintinib, vandetanib, and panitumumab were the top 5 drugs with high risk. Non-antitumor drugs were all moderate risk, involving atorvastatin, zoledronic acid, amiodarone hydrochloride, lithium, and teduglutide...The number of related adverse event reports increased year by year. The results of this study provided the relevant basis for pharmacovigilance, and provided the basis for strengthening drug safety and making correct drug decision in clinical practice.

P2, N=30, Active, not recruiting, Shanghai Chest Hospital | Recruiting --> Active, not recruiting | Trial completion date: Dec 2022 --> Dec 2027

The drug sensitivity analysis showed that dacomitinib and talazoparib may serve as anti-ESCC drugs through targeting MAPK14. The in vitro experiments showed that knockdown of NEURL3 inhibited the proliferation and motility of ESCC cells. Based on the URGs and DRGs prognostic signature, a novel nomogram was constructed that could serve as a potentially reliable prognostic model and provide theoretical basis for uncovering potential therapeutic target in the treatment of ESCC.