1328P - Analysis of data from the AENEAS study assessing the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), aumolertinib, and virtual comparison with osimertinib

Background

TKIs targeting the EGFR revolutionized care of patients (pts) with non-small cell lung cancer (NSCLC) harboring EGFR mutations. Resistance to 1^st/2^nd-generation EGFR TKIs inevitably develops, with clone(s) harboring T790M EGFR mutations emerging in 50–70% of cases. 3^rd-generation EGFR TKIs active against T790M and common EGFR-activating mutations are in development; only osimertinib and aumolertinib have regulatory approvals.

Methods

We have described a novel approach for assessing treatment efficacy using measurements of tumor burden to estimate rates of growth and regression of tumors designated g and d , respectively. Data from thousands of pts with diverse tumors have shown g is inversely correlated with OS. We analyzed data from the randomized phase III AENEAS study comparing aumolertinib with gefitinib.

Results

94% of the data could be analyzed; notably more pts than included for the primary PFS endpoint. Tumor growth reflected in a detectable g was found in 89% of both arms, including many not scored as progression. Superiority of aumolertinib was evident in statistically slower g values [and longer tumor doubling times, TDT] for aumolertinib [ g = 0.0006/day (0.0005-0.0011); TDT 1155 days] than gefitinib, [ g = 0.0012/day (0.0007-0.0020); TDT, 578 days], p<0.0001. Aumolertinib was superior in slowing g in tumors with Ex19del alterations compared to L858R mutations [p=0.0018], and superior to gefitinib in slowing g in tumors with Ex19del alterations [p<0.0001] just missing significance for L858R mutations [p=0.0687] – possibly due to smaller number of pts. Aumolertinib slowed g in non-smokers compared to smokers [p=0.0066] and superior to gefitinib in slowing g in non-smokers [p<0.0001]. Finally, g values with aumolertinib were comparable to published osimertinib values. Table: 1328P

Median rate of tumor growth (g) by line and type of therapy

*1^st generation EGFR inhibitors, gefitinib or erlotinib

Conclusions

Like osimertinib, aumolertinib is a highly effective third-generation EGFR-TKI.

Clinical trial identification

NCT03849768.

Editorial acknowledgement

Legal entity responsible for the study

Hansoh Pharmaceutical Group Co, Ltd.

Funding

Has not received any funding.

Disclosure

S. Lu: Financial Interests, Institutional, Invited Speaker: Hansoh, AstraZeneca, Roche, Hengrui; Financial Interests, Institutional, Advisory Board: AstraZeneca, Pfizer, Boehringer Ingelheim, Hutchison MediPharma, ZaiLab, GenomiCare, Yuhan Corporation, Menarini, InventisBio Co. Ltd, Roche, Simcere Zaiming Pharmaceutical Co., Ltd.; Financial Interests, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui, Roche, Hansoh, BeiGene, Lilly Suzhou Pharmaceutical Co. Ltd; Financial Interests, Coordinating PI: FibroGen. H. Wei: Financial Interests, Institutional, Full or part-time Employment, Medical staff: Hansoh Pharmaceutical Group Co, Ltd.. S.E. Bates: Financial Interests, Personal, Advisory Role: Pegascy, ElmediX, Servier, OnKure, Ipsen; Financial Interests, Institutional, Licensing Fees or royalty for IP: Deacetylase Inhibitor Therapy, Depsipeptide for Therapy of Kidney Cancer; Financial Interests, Personal, Research Funding: Pfizer; Financial Interests, Institutional, Research Funding: Merck, Amgen, RenovoRx, Ipsen, Pfizer. L. Schwartz: Financial Interests, Personal, Advisory Role: Novartis, Regeneron, Bristol Myers Squibb/Celgene; Financial Interests, Personal, Royalties: Varian Medical Systems; Financial Interests, Institutional, Research Funding: Merck Sharp & Dohme, Boehringer Ingelheim. A.T. Fojo: Financial Interests, Personal, Financially compensated role: Merck; Financial Interests, Personal, Advisory Role: Akita Biomedical; Financial Interests, Institutional, Research Funding: Ipsen, Pfizer, Merck. All other authors have declared no conflicts of interest.