ASCO 2025: REZILIENT1 Insights From Dr. Helena Yu

Helena Yu, MD, of the Memorial Sloan Kettering Cancer Center, joined Lung Cancers Today at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting to share insights from her oral abstract presentation on REZILIENT1. The study explored the efficacy of zipalertinib in patients with non-small cell lung cancer (NSCLC) who have EGFR exon 20 insertion mutations and who have undergone prior platinum-based chemotherapy with or without amivantamab.

“We were pleased to see that the results from the phase 1 study were recapitulated in this phase 2 study,” she explained. “For the patients that had prior chemotherapy only, but no prior exon 20-targeting drugs, the overall response rate was 40%, which is what we saw in the initial phase 1 study.”

Among patients who had received prior amivantamab, the overall response rate was 30%. However, for patients who received amivantamab with another EGFR exon-20-targeting medication, such as mobocertinib, sunvozertinib, BLU-451, or poziotinib, the response rate was reported to be 14.3%.

“I think that makes sense because if you give a medicine very similar to zipalertinib, there likely will be some cross-resistance,” she said. “I think what was reassuring and nice to see is that there was not that cross-resistance between the EGFR-MET antibody amivantamab with the tyrosine kinase inhibitor zipalertinib.”

The study also evaluated the results among patients who presented with brain metastases. Dr. Yu explained that 40% of patients across all cohorts had brain metastases, the majority of which were untreated, which was important to evaluate response.

“In EGFR-mutant lung cancer, more than half of patients will ultimately develop brain metastases,” she said. “When we’re evaluating potential treatments, we need to know how efficacious they are in the central nervous system…. We saw that the response rate in patients who had brain [metastases] was equivalent to the overall general response rate. When that happens, we suspect that there is good [central nervous system] penetration of the drug.”

Dr. Yu concluded by emphasizing the significance of these results for the patient population and the overall impact of the findings on oral-targeted therapies in the lung cancer treatment landscape.

“We have amivantamab, which is definitely an active drug, but we want more options for our patients,” she explained. “These patients live longer, and so having multiple treatment options is helpful. We want an oral, well-tolerated treatment option, and I think that’s what our patients want, something that has less toxicity…. The convenience of oral therapies, where you don’t have to come in weekly for every other treatment, really is key, and I think they want to live longer, but they want to live well.”