Dr Reckamp on Emerging EGFR TKIs in EGFR Exon 20 Insertion+ NSCLC

Karen L. Reckamp, MD, MS, director, Division of Medical Oncology, associate director, Clinical Research, medical oncology director, Lung Institute, Cedars-Sinai, discusses emerging data for next-generation EGFR TKIs in the treatment of patients with non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations.

Reckamp highlights recent data for 2 novel EGFR TKIs presented, emphasizing their potential in this patient population.

First, the phase 2 WU-KONG1 study (NCT03974022) investigated sunvozertinib (DZD9008) in patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations who received prior treatment with platinum-based chemotherapy. Findings presented at the 2024 ASCO Annual Meeting showed that at the data cutoff of March 22, 2024, the best objective response rate (ORR) was 53.3% (95% CI, 42.0%-64.3%) in patients treated with sunvozertinib at 300 mg once per day (n = 107). The confirmed ORR was 44.9% (97.5% CI, 34.0%-56.1%). Two patients (1.9%) achieved a confirmed complete response (CR), and a third CR was unconfirmed. The median duration of response (DOR) was not been reached, and the 9-month DOR rate was 57%. Notably, responses were observed regardless of prior amivantamab-vmjw (Rybrevant) treatment. The best ORR in patients previously treated with amivantamab was 50%, and those naive to amivantamab had a best ORR of 53.8%.

Second, a global phase 1/2a study (NCT04036682) investigated zipalertinib (CLN-081; TAS6417) in patients with recurrent or metastatic EGFR exon 20 insertion–mutated NSCLC previously treated with platinum-based chemotherapy. Results published in the Journal of Clinical Oncology showed that responses occurred across all dose levels of zipalertinib, which ranged from 30 mg to 150 mg twice per day. Among all response-evaluable patients (n = 73), the confirmed partial response (PR) rate was in 38.4% (95% CI, 27%-49%). At the 100-mg dose level (n = 39), the confirmed PR rate was 41% (95% CI, 25%-56%).

Reckamp emphasizes the importance of understanding the differing mechanisms of action among these new-generation TKIs compared with other therapies, such as amivantamab. This distinction is crucial, suggesting the potential for sequencing these agents without the risk of cross-resistance, potentially expanding treatment options and improving outcomes for patients with EGFR exon 20 insertion–mutated NSCLC, Reckamp concludes