Ameile (aumolertinib)

Our study concluded that combination regimens based on third-generation TKIs (osimertinib plus ramucirumab, osimertinib plus chemotherapy, osimertinib plus bevacizumab, amivantamab plus lazertinib and aumolertinib plus apatinib) could be the new and clinically preferable first-line, standard of care for EGFR-mutated advanced non-small cell lung cancer.

Third-generation TKIs, such as osimertinib, almonertinib and furmonertinib, are effective for the treatment of NSCLC that is EGFR-sensitizing mutation-positive and T790M-positive. To the best of our knowledge, the present report describes the first case of a patient with lung adenocarcinoma who had multiple co-existing EGFR resistance mutations, including EGFR L718Q, EGFR C797S, EGFR C797G, EGFR L792H, EGFR V802F and EGFR V689L. These mutations conferred resistance to almonertinib, whilst maintaining sensitivity to afatinib.

P2, N=0, Withdrawn, Sun Yat-sen University | N=85 --> 0 | Recruiting --> Withdrawn

P3, N=624, Active, not recruiting, Jiangsu Hansoh Pharmaceutical Co., Ltd. | Recruiting --> Active, not recruiting | Trial primary completion date: Jan 2024 --> Jun 2024

This review included 23 randomized clinical trials incorporating 7,006 patients and 11 treatments: erlotinib, gefitinib, icotinib, afatinib, dacomitinib, osimertinib, furmonertinib, aumolertinib, pemetrexed-free chemotherapy (PfCT), pemetrexed-based chemotherapy (PbCT) and placebo. Difference in safety between the third-generation EGFR-TKIs was also first investigated comprehensively. Furthermore, this review elaborated the varied predominate spectrum and ranked the toxicity of EGFR-TKIs for providing toxicity rationale for treatment decisions.

Quantitative ion pairs were m/z 569.3 → 72.2 for furmonertinib and m/z 526.5 → 72.2 for aumolertinib, which was used as the internal standard (IS). The established analytical methods showed great sensitivity, simplicity, accuracy and reliability for the analysis of furmonertinib in human plasma and CSF. This assay would be helpful to predict the effectiveness and toxicities of furmonertinib in the pursuit of precision medicine for lung cancer patients.

Aumolertinib combined with anlotinib can effectively inhibit NSCLC cell proliferation by downregulating the PI3K-Akt pathway, suggesting a potentially new option for NSCLC treatment.

P=N/A, N=800, Recruiting, Fudan University | Not yet recruiting --> Recruiting

P3, N=192, Active, not recruiting, Jiangsu Hansoh Pharmaceutical Co., Ltd. | Trial primary completion date: Jan 2026 --> Jul 2024

P=N/A, N=4000, Completed, Fudan University | N=500 --> 4000

This case represents the first documented successful treatment of ARDS induced by EGFR E19 mutated NSCLC using almonertinib. The favorable clinical response observed in this critically ill patient suggests that almonertinib may be a viable therapeutic option for managing severe complications in NSCLC. Further research is necessary to corroborate these findings and optimize dosage and toxicity management strategies for broader clinical application.

Aumolertinib demonstrated superior progression-free survival (PFS) and a well-tolerated toxicity profile compared to gefitinib in front-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in the AENEAS trial. In this real-world study, aumolertinib showed comparable disease control and objective response rates as reported in the AENEAS trial for advanced NSCLC patients with EGFR-sensitizing mutations. Aumolertinib treatment improved PROs, further supporting it in first-line clinical practice.

P=N/A, N=500, Completed, Fudan University

Sensitivity and scenario analyses were performed to explore the robustness of the model. Compared with gefitinib, aumolertinib yielded an additional 0.941 expected life-years and 0.692 quality-adjusted life-years (QALYs), with an incremental cost of $18,855.55 over a 20-year time horizon. The incremental cost-effectiveness ratios were $20,051.67/life-year and $27,272.29/QALY, that below the willing-to-pay threshold of $38,223.34/QALY. Aumolertinib was a cost-effective alternative first-line treatment for patients with epidermal growth factor receptor-positive advanced nonsmall-cell lung cancer in China.

P=N/A, N=800, Not yet recruiting, Fudan University

P1, N=13, Terminated, Jiangsu HengRui Medicine Co., Ltd. | N=345 --> 13 | Recruiting --> Terminated; Sponsor R&D strategy adjustment

P1, N=20, Not yet recruiting, Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.

P2, N=85, Recruiting, Sun Yat-sen University | Not yet recruiting --> Recruiting

Overall, the method proved to be sensitive, reliable, and straightforward, enabling successful simultaneous determination of blood concentrations of icotinib, osimertinib, aumolertinib, and anlotinib in patients. The validity of the method has been confirmed across various instruments.

The patient achieved partial remission and did not show any further progression during the follow-up period. For NSCLC patients with both EGFR mutation and HER2 amplification, the combination of almonertinib and pyrotinib is a valuable therapy that can continuously reduce tumor burden and achieve long-term survival.

Furthermore, baicalein combined with almonertinib results in massive accumulation of reactive oxygen species (ROS) and preincubation with N-acetyl-L-cysteine (ROS remover) prevents proliferation as well as inhibits apoptosis induction, with partial recovery of the decline of p-PI3K and p-Akt. The combination of baicalein and almonertinib can improve the antitumor activity in almonertinib-resistant NSCLC through the ROS-mediated PI3K/Akt pathway.

Ba/F3 cells with an osimertinib-resistant secondary mutation were refractory to all 3G TKIs tested (alflutinib, lazertinib, rezivertinib, almonertinib, and befotertinib)...HCC827BIR cells had MET gene amplification and were sensitive to a combination of capmatinib (MET-TKI) and BI4020...This study suggests that erlotinib may be more suitable than 4G TKIs to overcome secondary mutations after front-line osimertinib. We found that off-target mechanisms that cause resistance to earlier-generation TKIs will also cause resistance to 4G TKIs.

These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases.

P2, N=60, Not yet recruiting, shanghai pulmonary hospital; shanghai pulmonary hospital

The result of patient treatment demonstrated the potential feasibility of neoadjuvant Aumolertinib monotherapy for locally advanced LUSQm. The report provides some support for neoadjuvant target-therapy for LUSQm.

P=N/A, N=30, Recruiting, Chongqing University Cancer Hospital

P1/2, N=156, Not yet recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd.

P2, N=60, Not yet recruiting, Shanghai Pulmonary Hospital, Shanghai, China

Following the lobectomy, the patient received treatment with almonertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), and at the latest follow-up, the patient has achieved partial remission...It stresses the importance of acquiring a comprehensive family history and performing genetic testing on leukocytes. Moreover, for the infrequent EGFR R776H mutation, third generation EGFR-TKIs may be a viable option.

P2, N=91, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

P2, N=6000, Recruiting, Hunan Province Tumor Hospital | Phase classification: P --> P2 | N=100 --> 6000 | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2026

These findings suggest that almonertinib and alflutinib may be potential therapeutic options for non-small cell lung cancer patients with the EGFR S768I mutation.

P2/3, N=1080, Not yet recruiting, Hansoh BioMedical R&D Company

P3, N=8, Terminated, EQRx International, Inc. | Phase classification: P3b --> P3

Furthermore, subsequent-line treatment multivariate Cox regression analysis showed a statistically significant impact of elevated creatine kinase on median PFS (p = 0.026) and a significant effect on the number of metastatic organs (p = 0.017), co-mutation (p = 0.035), and elevated creatine kinase (p = 0.014) on median OS. Aumolertinib has shown clinical significance and can safely be used in the real-world setting for patients with EGFR mutation-positive NSCLC.

P2, N=63, Active, not recruiting, Zhejiang Cancer Hospital | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2024 --> Jun 2024

P2, N=56, Active, not recruiting, Shanghai Pulmonary Hospital, Shanghai, China | Recruiting --> Active, not recruiting

P2, N=22, Recruiting, The First Affiliated Hospital of Guangzhou Medical University | Not yet recruiting --> Recruiting

Pharmacological inhibition of MMP-9 could overcome resistance to almonertinib, as evidenced in both in vitro and in vivo models. Our findings suggest that LCN2 was a crucial regulator for conferring almonertinib-resistance in NSCLC and demonstrate the potential utility of targeting the LCN2-MMP-9 axis for clinical treatment of almonertinib-resistant lung adenocarcinoma.

P2, N=85, Not yet recruiting, Sun Yat-sen University

P2, N=108, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

We reported a patient with lung adenocarcinoma who developed EGFR-T790M mutation after first-line treatment with icotinib and sarcoma transformation after second-line treatment with almonertinib. Sarcoma transformation can be one of the forms of drug resistance in patients with lung adenocarcinoma with EGFR-TKIs. The prognosis of patients with adenocarcinoma after transformation into sarcoma is poor.