ASCO 2026 | AcceleRET-Lung: pralsetinib vs SOC in first-line RET fusion-positive NSCLC

So at ASCO here in Chicago in 2026, I was delighted to present results of the AcceleRET-Lung lung trial. This is a randomized phase three trial of pralsetinib versus standard of care chemo plus minus immunotherapy in patients with RET fusion positive advanced non-small cell lung cancer. We know that RET fusion is occurring up to 2% of patients. And previously, the single arm ARROW study evaluated pralsetinib. And that resulted in full FDA approval for pralsetinib for patients with RET fusion advanced non-small cell lung cancer with response rates of about 70% duration of response just over 20 months. So the AcceleRET-Lung phase three trial was designed to test the efficacy and evaluate the safety of pralsetinib versus standard of care, which hadn’t been formally evaluated at that time point. So the study was designed as a randomized phase three study. Patient eligibility was patients with RET fusions. Patients were eligible if they had performance status 0 or 1. No prior systemic therapy. And patients with CNS metastases were eligible if they were active but asymptomatic and stable. Patients were randomized to either the interventional arm of pralsetinib 400 milligrams daily or the control arm of histology-specific chemotherapy with or without pembrolizumab. Patients in the control arm were allowed to cross over to pralsetinib upon progression. The primary endpoint of the study was progression-free survival, and key secondary endpoints included duration of response, overall response rate, safety, and overall survival. A total of 233 patients were powered for progression-free survival. But unfortunately, the study was prematurely terminated by the sponsor at the time, the original sponsor, at nearly 99% of overall study accrual. When we look at the demographics of the population, they were very well balanced and typical of a RET population, relatively young for a lung cancer population and predominantly and nearly exclusively adenocarcinoma. They were, however, a slightly poorer prognostic group than we’ve seen with some RET cohorts. We had about 30% of patients with CNS metastases and 40% of patients were smokers or ex-smokers. When we look at the primary endpoint, the primary endpoint was met. Pralsetinib resulted in a statistically significant and clinically meaningful progression-free survival benefit over standard of care treatment with a hazard ratio of 0.59, translating to a 41% relative improvement in risk of progression or death. The median progression-free survival is just over 18 months for pralsetinib compared to about nine months with standard chemotherapy. When we look at the multivariable analysis, we can see that all major prognostic groups derived benefit with the point estimates of the hazard ratio over to the left of unity and overlapping confidence intervals. Key secondary endpoints were met with a significant improvement in response rate for pralsetinib over chemotherapy, about 65%. and this translated to a durable duration of response, which is statistically significant, just over 20 months compared to chemotherapy. Now, overall survival was not statistically significant. That’s no surprise. It was immature at the point of the study closure, with only 30% of expected events events and 34% of patients crossed over from the control arm to the investigative arm confounding analysis as well. When we look at safety, we see that there were predominantly grade one and grade two adverse events noted and the discontinuation rate was about 16%. Grade three adverse events we’re seeing were predominantly hypertension, anemia, neutropenia, and pneumonia. When we evaluated this further, we did see an increased treatment-related adverse event rate for pralsetinib. Indeed, further pharmacovigilance identified that serious infection was a key safety concern. We identified that there were eight patients who had passed away with significant infections in the pralsetinib arm which were unexpected. This prompted a urgent safety protocol amendment and this resulted investigators being informed of the risks of infection and guidance around dose reduction and dose discontinuation contingent on the grade of infection, AE, that was identified. Further safety review following the protocol implementation demonstrated that none of the residual patients that were on pralsetinib had any further infection-related deaths. And further analysis of the sponsor’s global safety database identified no additional, well, one additional death following the protocol amendment. Evaluation of the FDA safety database identified no additional infection-related deaths. So in summary, AcceleRET-Lung Study is a randomized phase three study, which confirms the data from Arrow insofar as it confirms the efficacy and safety of pralsetinib over standard of care with the statistically significant and clinically meaningful benefits of pralsetinib over standard of care with a hazard ratio of 0.59. The safety concern of serious infection was identified but seems to have been successfully mitigated by raising this with investigators and for pharmacovigilance and dose reductions and discontinuations contingent on the infection grade of adverse event identified.

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