The European Lung Cancer Congress (ELCC 2024) will be held in Prague, the capital of the Czech Republic, from March 20 to 23, 2024, and six innovative achievements on Hansoh Pharma’s original novel drug Aumolertinib have been selected to be presented at this congress. By virtue of its great innovative strength, Hansoh Pharma will continue to explore more treatment regimens for lung cancer patients in China and throughout the world.

Co-organized by the European Society for Medical Oncology (ESMO) and the International Association for the Study of Lung Cancer (IASLC), the ELCC is one of the most prominent international academic conferences in the field of lung cancer. At the congress, clinical and research experts from all over the world gather together to present the progress of their innovations in the field of lung cancer and discuss the direction of the development of lung cancer treatments.

A total of six Aumolertinib innovations were selected for the congress, including the latest updates on use of Aumolertinib in the treatment of patients with unresectable stageⅢ NSCLC, adjuvant treatment of patients with stage IA2-IIIA NSCLC, adjuvant treatment of patients with stage I-III NSCLC (including high-grade structures), first-line treatment for prevention of NSCLC brain metastasis, as well as Aumolertinib in combination with Anlotinib for the treatment of patients with TP53 mutations in NSCLC, and Aumolertinib used in combination with local radiotherapy for the treatment of patients with oligometastatic NSCLC.

1. Efficacy and Safety of Aumolertinib (AUM) With Radiotherapy Versus Concurrent Chemoradiotherapy (cCRT) in the Treatment of Unresectable Stage III EGFR-mutant NSCLC: A Multicenter, Randomized, Open-Label Phase III Study (ADVANCE)

Authors: Nan Bi, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China; L.H. Wang, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Shenzhen, China

Number：2024 ELCC 143P

Eligible pts were aged 18-75 years old, histologically confirmed as unresectable stage III EGFR-mutant NSCLC, who were randomized into experimental group (Group A) and control group (Group B). Group A: AUM (110mg PO QD) for 9 weeks as induction therapy, followed by radiotherapy (60 Gy) +AUM, and AUM maintenance therapy. Group B: Radiotherapy (60Gy)+Cisplatin (75 mg/m2) + Pemetrexed (500 mg/m2) Q3W for 2 cycles, followed by Pemetrexed+ Cisplatin Q3W for 1-2 cycles. After progression in Group B, crossover to Group A was allowed. The primary endpoint was PFS. Partial secondary endpoints included OS, safety and quality of life.

40 pts (ITT) were enrolled, with 24 pts in Group A and 16 pts in Group B. At data cut-off (Dec,2023), the hazard ratio (HR) for PFS was 0.152 [95%CI 0.040-0.0579; p=0.0002]. The mPFS was NR for Group A vs 6.2 months for Group B, with the median follow-up time 11.2m vs 5.7m. The 12-months PFS rate was 87.0% in Group A. In Group B, eight pts had progressed. Of these pts, 4/8 (50%) had crossed over, while 3/8 (37.5%) of the pts did not, and 1/8 (12.5%) had died. OS was not reached. Grade 3 or higher (G3+) AEs occurred in 4.2% of Group A and as high as 25% of Group B. The most common TRAEs were muscular pain (12.5%; grade 1/2) and cough (8.3%; gradel), versus myelosuppression (27%; grade 3,13%) and vomiting (13%, grade2), respectively.

For pts with unresectable EGFR-mutated stage III NSCLC, the combination of AUM and radiotherapy provides better PFS benefit versus cCRT with fewer symptomatic AEs. Our study is still ongoing to extend the follow-up period to determine longer-term outcomes.

2. Adjuvant Aumolertinib for Resected EGFR-Mutated Stage IA2-ⅢA Non-Small-Cell Lung Cancer: Updated Results From A multiple-center real-world experience

Authors: J. Hu / Q. Zhang, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, China

Number：2024 ELCC 126P

Patients who underwent radical surgery for EGFR-mutated NSCLC with stage IA2-ⅢA were enrolled from four different medical centers. They received aumolertinib 110 mg once daily for 6 months to 3 years, depending on the pathological stage and individual physical conditions. The disease-free survival (DFS), safety and tolerability were evaluated. Patterns of recurrence and CNS DFS were prespecified exploratory end points.

The retrospective analysis included 290 patients who underwent radical surgery, and were pathologically diagnosed with adenocarcinoma, EGFR mutation-positive, and stage IA2-ⅢA NSCLC. At the data cutoff (December 11, 2023), the median follow-up was 19.2 months. The 3-year DFS rate was 92.4% in the overall population. For stage I(IA and IB) and II-IIIA disease,the 3-year DFS rate was 91.7%(91.7% and 100%) and 91.2%,respectively. CNS recurrence occurred in only one patient in the overall population, and 3-year CNS DFS rate was 99%. The estimated probability of observing CNS recurrence at 36 months was 1% in the overall population and 2.5% in stage IB-IIIA disease, respectively. During aumolertinib treatment, no adverse events of grade≥3 were reported. Among the 290 patients, 104 patients (35.9%) experienced drug-related adverse reactions, with rash (50/290, 17.2%), diarrhea (16/290, 5.5%), abnormal liver function (18/290, 6.2%), and oral ulcer (17/290, 5.8%) being the most common.

These updated data further underscore the pronounced efficacy of aumolertinib in the postoperative adjuvant treatment of NSCLC, accompanied by an excellent safety profile. Long term follow-up for our study is ongoing to explore additional survival outcomes.

3. Aumolertinib as adjuvant therapy in postoperative EGFR-mutated stage I–III non-small cell lung cancer with high-grade patterns

Authors: W. Shen / X. Chen, Ningbo Medical Center LiHuiLi Hospital, Ningbo, China; H. Shen, The Second Hospital of Ningbo, Ningbo, China

Number：2024 ELCC 115P

EGFRm stage I–III NSCLC patients who underwent radical surgery with high-grade patterns (micropapillary, solid component or complex glands) were enrolled. EGFRm patients were assigned into aumolertinib group (group A) receiving aumolertinib (110 mg daily) treatment and observation group (group B). EGFR mutation negative or unknown were assigned into Group C also receiving observation. We evaluated disease-free survival (DFS) and safety. DFS was evaluated based on pathological stage or proportions of high-grade patterns.

A total of 136 stage I–III NSCLC patients with high-grade patterns (59 pts in Group A, 25 pts in Group B;52 pts in Group C) were enrolled. At data cut-off, the median follow-up was 15.4 months in Group A ,26.5 months in Group B and 30.1 months in Group C. Tumor recurrence occurred in only 1 patient in group A. The 2-year DFS rate was 98% in Group A,73% in Group B and 87% in Group C. For patients with stage I in Group A, the 2-year DFS rate was 100%. The DFS of Group A was significantly better than that of Group B (P=0.0178). When stratified by stage and the proportion of high-grade patterns, the DFS of Group A with stage I (p=0.0134), stage IB(p=0.0394) or stage IA with no less than 5% of high-grade patterns(p=0.0272) was also significantly better than that of group B. Compared Group B and C, the recurrent ratioin in EGFR mutated patients was higher than those with EGFR negative or unknown. No AEs of grade≥3 occurred during aumolertinib treatment. 44.1% (26/59) of patients experienced drug-ralated adverse reactions, with the most common being pruritus (22.8%), rash (12.3%), and oral ulcer (7.0%).

This study is the first to demonstrate that EGFRm stage I–III NSCLC patients with high-grade patterns can benefit from aumolertinib adjuvant therapy. The updated results further demonstrate that patients in stage IA with≥5% high-grade patterns and IB with high-grade patterns can obtain survival benefit from aumolertinib therapy. Long-term follow-up of our study is ongoing to investigate further survival outcomes.

4. Preventing CNS Metastasis in EGFR-mutant NSCLC patients Without Baseline CNS Metastasis UsingAumolertinib

Author: Fang Shen Cun, Nanjing Chest Hospital

Number：2024 ELCC 18P

All consecutive first-line aumolertinib-treated EGFR-mutant advanced NSCLC patients without baseline CNSmetastasis after drug registration (April 2020 to February 2023) were included. The cumulative incidence ofsubsequent symptomatic CNS metastases, CNS mPFS, and their risk factors were estimated using the Kaplan–Meier method and the log-rank test.

Data were retrieved from 63 patients who all received aumolertinib monotherapy as first-line treatment. Themedian follow-up was 27.4 months. There were 10 pts who developed symptomatic CNS metastases.The CNSmPFS was not reached, with the 12, 18, and 24-month CNS mPFS rate being 100% ,96.3% ,and 93.6%,respectively. The cumulative incidence of symptomatic CNS metastasis at 12, 18, and 24 months were0%,3.7%, and 6.4 %, respectively. The cumulative incidence with aumolertinib was lower than historical datafrom first-generation EGFR-TKIs as first-line treatment (2.8-13.9% at 12 months; 9.3-34.6% at 24 months). Moreover, aumolertinib showed equivalent advantages in delaying symptomatic CNS metastasis in patientswith L858R and 19del mutations (p=0.9345). Patients with concurrent TP53 mutations, especially mutations inexons 5 or 8, exhibited a higher risk of developing CNS metastasis than those without TP53 mutations or withan unknown status (p=0.0324)

This is the first study to suggest that aumolertinib can reduce the risk of CNS metastasis and prolong CNSdisease control in untreated NSCLC patients without baseline CNS metastasis better than first-generation TKIs.

5. Safety and Efficacy of Aumolertinib Combined With Anlotinib as 1st Line Treatment in Advanced Lung Cancer EGFR Mutation With TP53 Co-Mutation

Author: Z. Pan / Z. Jiang, Tianjin Medical University Cancer Institute and Hospital

Number：2024 ELCC 98TiP

This is a phase II clinical study with a single-arm, exploratory design. 47 patients are scheduled to be enrolled. The key inclusion criteria are as follows:1) Locally advanced or metastatic NSCLC EGFR sensitive mutations (19del and L858R) and TP53 co-mutation; 2) Have not received systematic treatment; If the subject has received adjuvant therapy after completing radical treatment for early NSCLC and the subject has relapsed disease, ensure that the end of adjuvant therapy is more than 6 months from the first dose of the study and that various toxicities due to the adjuvant therapy have recovered; 3) ECOG 0-1, The expected survival is more than 6 months; 4)At least one assessable lesion (RECIST 1.1 ).Treatment regimen is aumolertinib 110mg p.o. QD daily and anlotinib 12mg p.o. QD for 2 weeks, three weeks a cycle, until disease progression or intolerable adverse reactions or death. The primary endpoint is progression free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. In addition, we also try to explore predictive or prognostic biomarkers (tissue and/or plasma) related to disease treatment response or drug resistance. Analyze the potential biomarkers in the biopsy tissue samples and blood samples after the disease progresses, and explore the possible mechanism of treating drug resistance. The first patient had been enrolled in February, 2022.

6. Phase II Study of Aumolertinib Combined with Local Radiation Therapy for EGFR Mutated StageⅣNSCLC Patients with oligometastasis

Author: Fen Zhao, Shandong Cancer Hospital and Institute

Number：2024 ELCC 100TiP

Approximately 60 stage IV EGFR-mutated oligometastatic NSCLC patients will be enrolled in this study. After 8 weeks of induction therapy with aumolertinib(110mg/day), patients will be randomly divided into two groups. The first group continue to receive aumolertinib monotherapy, and the second group patients will be assigned to receive intensity-modulated radiotherapy and then continue to administrate receive aumolertinib. All the patients are permitted to continue treatment until unacceptable toxicity or disease progression. The primary endpoint is PFS.

The innovation of this project is that the advantage population of combining aumolertinib with local radiotherapy can be screened; Secondly, Previous studies have combined local treatment after disease progression, but the accumulation of malignant clones at this time may increase the risk of progression and subsequent metastasis. The early addition of local radiotherapy is expected to reduce the occurrence of this risk. However, combination radiation therapy may increase the damage to the surrounding normal tissue if the tumor is large at initial diagnosis. This study evaluates that if the intensity-modulated radiotherapy has good synergistic effect when the lesions have the response to aumolertinib, and whether the combined treatment can delay the time to progression (TTP) and OS or not.