1317MO - Updated study results of pelcitoclax (APG-1252) combined with osimertinib in patients (pts) with EGFR-mutant non-small cell lung cancer (NSCLC)

Background

Investigational agent pelcitoclax is a dual BCL-2/BCL-xL inhibitor that enhances antitumor effects of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) osimertinib in preclinical models. In pts with TKI-naïve EGFR-mutant NSCLC, pelcitoclax plus osimertinib was well tolerated and showed preliminary efficacy (Zhang L et al. J Clin Oncol 2022 ). Here, we provide updated safety and efficacy results of this combination therapy.

Methods

The recommended phase 2 dose of pelcitoclax was established at 160 mg weekly plus osimertinib 80 mg daily. After completion of dose escalation and 2 dose expansions, pts were divided into 3 cohorts by treatment line: Cohorts 1 and 2 (EC-1 and EC-2) included pts with disease resistant to first- and third-generation EGFR-TKIs, respectively; Cohort 3 (EC-3) included pts whose disease was previously untreated with EGFR-TKIs.

Results

As of February 16, 2023, 64 pts (median age, 56 years; 54% female) were treated with pelcitoclax plus osimertinib. Among them, 8 were in EC-1, 29 in EC-2, and 27 in EC-3. Among 26 efficacy-evaluable pts in EC-3, 20 partial responses (PRs [76.9%]) were observed. For pts with TP53 and EGFR-positive mutations in EC-3, 13/16 (81.3%) PRs were observed, and the median progression-free survival (range) was 16.39 (8.11-NR) months. Preliminary biomarker data from pts in EC-2 suggested that high BCL-xL expression was associated with antitumor efficacy. A total of 64 (100%) pts in all cohorts experienced treatment-related adverse events (TRAEs), which were grade ≥ 3 in 12 (18.8%). Common TRAEs included increased aspartate aminotransferase (70.4%) and alanine aminotransferase (59.3%), reduced platelet counts (33.3%), increased serum amylase (25.9%), and increased blood creatinine (22.2%).

Conclusions

Based on these findings, pelcitoclax plus osimertinib is of potential clinical interest to improve outcomes of pts with TP53- and EGFR-mutant NSCLC. Further studies are needed to elucidate the role of pelcitoclax when combined with osimertinib in treating this pt population. Internal study: APG1252NC101; CT.gov: NCT04001777.

Clinical trial identification

NCT04001777.

Editorial acknowledgement

Editorial support was provided by Ashutosh K. Pathak, MD, PhD, MBA, FRCP (Edin.), Stephen W. Gutkin, Ndiya Ogba, PhD, and Paul O. Fletcher, PhD, with funding from Ascentage Pharma Group Corp Ltd (Hong Kong).

Legal entity responsible for the study

Ascentage Pharma.

Funding

Ascentage Pharma Group Corp Ltd (Hong Kong).

Disclosure

L. Men: Financial Interests, Institutional, Full or part-time Employment: Ascentage Pharma; Financial Interests, Institutional, Stocks/Shares: Ascentage Pharma. E. Liang: Financial Interests, Institutional, Full or part-time Employment: Ascentage Pharma; Financial Interests, Institutional, Stocks/Shares: Ascentage Pharma. D. Yang: Financial Interests, Institutional, Leadership Role: Ascentage Pharma; Financial Interests, Institutional, Full or part-time Employment: Ascentage Pharma; Financial Interests, Institutional, Stocks or ownership: Ascentage Pharma. L. Zhang: Financial Interests, Institutional, Research Grant, research grant & Trial Chair: AZ; Financial Interests, Institutional, Research Grant: BMS, Roche; Financial Interests, Institutional, Trial Chair: QiLu Pharm, Henrui Pharm, Novartis, Hansoh Pharma, China Shiyao Pharma, Kelun Pharm. Y. Zhai: Financial Interests, Institutional, Leadership Role: Ascentage Pharma; Financial Interests, Institutional, Stocks or ownership: Ascentage Pharma; Financial Interests, Institutional, Full or part-time Employment: Ascentage Pharma. All other authors have declared no conflicts of interest.