Andamertinib Demonstrates Clinical Promise for Pretreated Patients With EGFR-Mutated NSCLC

Key Clinical Takeaways:

• Design/Population: The phase 2 KANNON study evaluated andamertinib for patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations who had progressed after platinum-based chemotherapy or immunotherapy.
• Key Outcomes: Andamertinib achieved a confirmed objective response rate of 42.7%, with durable responses and a median progression-free survival of 6.2 months. Activity was observed across a wide range of exon 20 insertion subtypes, including among patients with brain metastases.
• Clinical Relevance: These results support further development of andamertinib as a targeted treatment option for patients with EGFR exon 20 insertion-mutant NSCLC, a population with limited therapeutic options after prior systemic therapy.

According to results from the phase 2 KANNON trial, andamertinib demonstrated promising antitumor activity and manageable safety among patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations who experienced disease progression after platinum-based chemotherapy or immunotherapy. 

“Following disease progression after first-line platinum-based chemotherapy, therapeutic options are limited,” stated Jin-Ji Yang, PhD, Guangdong Lung Cancer Institute, Guangzhou, China, and coauthors. “This study aimed to evaluate [the efficacy of] andamertinib, a selective and irreversible tyrosine kinase inhibitor.” 

In this multicenter, single-arm trial, researchers enrolled 92 patients to receive 240 mg of once daily andamertinib in 28-day cycles until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). Key secondary end points included progression-free survival (PFS), overall survival (OS), and safety. 

At a median follow-up of 15.4 months, the confirmed ORR was 42.7%, with a disease control rate of 86.5% and a median duration of response of 8.7 months. Median PFS was 6.2 months, and median OS was not reached, with a 12-month survival rate of 70.5%. Among 38 patients with baseline brain metastases, the systemic confirmed ORR was 47.4%. Grade ≥ 3 treatment-related adverse events occurred in 40.2% of patients, most commonly diarrhea (12%) and rash (7.6%).

“Andamertinib demonstrated robust and durable antitumor activity in patients with advanced NSCLC harboring EGFR ex20ins mutations who had progressed on platinum-based chemotherapy or immunotherapy,” concluded Dr Yang et al. 

Source: 

Yang JJ, Mu Y, Wang ZH, et al. Andamertinib in advanced NSCLC with EGFR exon 20 insertions after platinum-based chemotherapy or immunotherapy: Results from the phase 2 KANNON study. J Thorac Oncol. Published online: November 15, 2025. doi: 10.1016/j.jtho.2025.11.008