KEY TAKEAWAYS
- The study aimed to investigate the efficacy and safety of zipalertinib in NSCLC with EGFR ex20ins after amivantamab.
- Researchers noticed that zipalertinib demonstrated promising efficacy and safety in patients with NSCLC.
Zipalertinib (CLN-081, TAS6417) is a novel EGFR tyrosine kinase inhibitor (TKI) that achieved a confirmed objective response rate (ORR) of 41% with manageable safety in a phase 1/2a study involving patients with Non-Small Cell Lung Cancer (NSCLC) EGFR exon 20 insertion (ex20ins) NSCLC who had received prior platinum-containing chemotherapy (JCO 2023).
Antonio Passaro and the team aimed to present data from the phase 2b REZILIENT1 study focusing on cohort C patients with EGFR ex20ins mutant NSCLC who progressed after treatment with amivantamab.
They performed an inclusive analysis involving patients who had progressed after at least 1 prior treatment, including amivantamab. These patients were enrolled to receive zipalertinib at a dosage of 100 mg orally twice daily. Tumor response was assessed by the investigator according to RECIST v1.1 criteria. Patients with stable, asymptomatic, or treated brain metastases were also permitted to participate in the study.
About the 29 March 2024 data cut-off (DCO), 45 patients had been enrolled, with a median age of 62 years (range 33-85) and a median of 3 lines of prior therapy (range 1-6). Prior treatment included platinum-based chemotherapy in 43 patients (96%), anti-PD1/L1 therapy in 20 patients (44%), and EGFR TKIs in 22 patients (49%). A history of brain metastasis was present in 22 patients (49%).
Treatment-related adverse events (TRAEs) occurring in ≥10% of patients included rash (38%), paronychia (36%), anemia (24%), dry skin (20%), dermatitis acneiform (16%), nausea (16%), and stomatitis (11%). Grade 3 TRAEs were reported in 14 patients (31%), including anemia (4), rash (3), and pneumonitis/ILD (3). There were no grade 4 or 5 TRAEs. TRAEs leading to dose reductions and discontinuations occurred in 3 patients (7%) each.
At DCO, 30 patients were evaluable for response (having at least 2 treatment assessments or progression/death), of which 1 patient (3%) achieved a complete response (CR), 11 patients (37%) had a partial response (PR), and 15 patients (50%) had stable disease (SD). The overall response rate (ORR) was 40%, and the disease control rate (CR + PR + SD) was 90%. The median duration of response was not yet estimable, and the median progression-free survival (PFS) was 9.7 months.
The study concluded that zipalertinib demonstrated promising anti-tumor activity and a manageable safety profile in heavily treated patients with NSCLC harboring EGFR ex20ins mutations who progressed after prior treatment with amivantamab. These findings support the potential of zipalertinib as a viable therapeutic option in this challenging patient population.
The trial was sponsored by Cullinan Therapeutics Inc.
Source: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/105
Clinical Trial: https://clinicaltrials.gov/study/NCT04036682
Passaro A, Yu H.A, Nguyen D, et al. (2024). “Safety and anti-tumour activity of zipalertinib in NSCLC patients (pts) with EGFR exon 20 insertion (ex20ins) mutations who received prior amivantamab.” Presented at ESMO 2024 (Abstract 1254MO).
