ESMO 2025 | ASPEN-04: evorpacept with pembrolizumab & chemotherapy in R/M HNSCC

So in the ASPEN-04 trial, what we tried to do was build upon the results of KEYNOTE 048 by combining Pembrolizumab with standard of care chemotherapy, so Platinum and 5-FU, and randomizing to conclude Evorpercept, an anti-CD47 drug, or not. So this study was in patients with relapsed head and neck cancer, relapsed or metastatic head and neck cancer, in the first-line setting. Patients with good performance status, good organ function, were offered randomization on a two-to-one fashion between an Evorpercept containing chemotherapy and Pembrolizumab regimen or just the chemotherapy and Pembrolizumab regimen on its own. So we recruited 165 patients randomized in that fashion two-to-one and the primary endpoint of this study was based upon overall response rate. The plan, the statistical analysis plan, was that we were going to compare the response rate documented in the experimental arm containing Evorpercept with the standard of care result from Keynote 048, which was published by Barbara Burtness in 2019. In that group of patients, the response rate was 36.4% for patients receiving chemotherapy plus pembrolizumab. So the results of this study showed that the experimental arm of 110 patients yielded a response rate of 37.3%, and that was not statistically significantly different from the control arm that was the Keynote 048 dataset. So the study failed to meet its primary endpoint. Moreover, when we compared the two arms in the study, which was allowed within the statistical analysis plan, we saw that actually the standard of care in the randomization here, the 55 patients who received chemotherapy and pembrolizumab, their response rate was about 45%. So in fact, it was numerically superior to the Evorpercept containing regimen, but not statistically significantly different from that regimen. When we compared progression-free and overall survival endpoints between the two arms, there was no statistically significant benefit in either direction. So overall, we have to conclude, sadly, that the addition of a CD47 targeted therapy to standard of care chemotherapy and immunotherapy does not yield improvements either in overall response, progression-free survival, or in overall survival. And sadly, the decision has been taken not to develop further this compound in that setting, in the first-line setting of patients with relapsed and metastatic head and neck cancer.

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