BCL-2/BCL-xL inhibitor pelcitoclax with osimertinib for EGFR-mutated advanced non-small-cell lung cancer: a phase 1b trial
Abstract
Background: Overcoming tyrosine kinase inhibitor (TKI) resistance improves survival in advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). We therefore examined the safety and preliminary efficacy of pelcitoclax, a B-cell lymphoma-2 (BCL-2)/BCL-extra-large (BCL-xL) inhibitor, and osimertinib in patients with EGFR-mutated advanced NSCLC.
Methods: Enrolled patients included Cohort 1 (previously progressed after third-generation TKI treatment+chemotherapy), Cohort 2 (previously progressed after first-generation or second-generation TKI treatment+chemotherapy), and Cohort 3 (TKI treatment-naive±prior chemotherapy). Patients received intravenous pelcitoclax (160 mg in dose-expansion and either 160 or 240 mg in dose-escalation) weekly and oral osimertinib 80 mg daily. Primary endpoints were safety and recommended phase 2 dose (dose-escalation), objective response rate (ORR) and safety (dose-expansion).
Results: 64 patients were enrolled (13, dose-escalation; 51, dose-expansion): 29 patients in Cohort 1, 8 in Cohort 2, and 27 in Cohort 3. One dose-limiting toxicity occurred at pelcitoclax 240 mg, and the recommended phase 2 dose was 160 mg plus osimertinib 80 mg. The ORR was 10.7% and median progression-free survival (mPFS) 2.7 months in patients previously progressed after third-generation TKI treatment+chemotherapy (Cohort 1) and 80.8% and 16.4 months in TKI treatment-naïve patients±prior chemotherapy (Cohort 3). mPFS was longer in Cohort…
How strong is the evidence?
Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 64 participants or records.
Read the paper
Related studies
- eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses
- Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer
- OptiType: precision HLA typing from next-generation sequencing data
- Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications
- Saccharomyces cerevisiae cells have three Omega class glutathione S-transferases acting as 1-Cys thiol transferases
- Hemolysis at low blood flow rates: in-vitro and in-silico evaluation of a centrifugal blood pump
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.