JCO at WCLC: Multinational Pivotal Study of Sunvozertinib in Exon20ins NSCLC

JCO fellow Dr. Ece Cali speaks with JCO Associate Editor Dr. Thomas E. Stinchcombe to discuss the JCO article "Phase 2 Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small-Cell Lung Cancer with Epidermal Growth Factor Receptor Exon 20 Insertion Mutations (WU-KONG1B)", that was simultaneously released at the IASLC 2025 World Conference on Lung Cancer.

TRANSCRIPT

Dr. Ece Cali: Hello, and welcome to our series where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year’s most important oncology meetings. I am your host, Dr. Ece Cali, JCO editorial fellow, and I am joined by Dr. Tom Stinchcombe, JCO associate editor, to discuss the Journal of Clinical Oncology article and 2025 World Conference on Lung Cancer abstract presentation, “Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non–Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations.”

The WU-KONG1B trial is a multinational, phase II study that investigated the efficacy and safety of different doses of sunvozertinib in patients with metastatic non-small cell lung cancer and EGFR exon 20 insertion mutations after progression on platinum based chemotherapy. Tom, before we dive into the results, could you walk us through the rationale for this study, and how does it fit into the current treatment options for patients with EGFR exon 20 insertion?

Dr. Tom Stinchcombe: Thank you, Dr. Cali. I think the clinical context is always important. We have known that EGFR exon 20 insertions exist and that they are resistant to our currently available EGFR tyrosine kinase inhibitors, and I think there have been attempts in the past to develop a tyrosine kinase inhibitor, but there is a very narrow therapeutic window between the dose you need to inhibit the EGFR mutation in the cancer and the EGFR receptor on normal tissues, most notably the mucosa, the gut, and the skin. And so, our previous attempts have failed largely because the dose required was not tolerable for patients and they could not really stay on the drug for a long time or they were not very active.

And so, I think there was a real desire to develop an EGFR tyrosine kinase inhibitor, and then, historically, the standard had been a platinum based doublet as the standard of care. And more recently, platinum based doublet with amivantamab has proven to be superior to platinum based chemotherapy alone. I think the context is also important that amivantamab is not necessarily available in all the countries, and so, there are patients who do not have access to amivantamab. Going to the rationale,