ALX Oncology’s phase 2 gastric cancer response rate has weakened. After seeing its CD47 blocker easily beat control over the first half of the trial, the biotech reported a much closer fight in the second part of the study—and investors were quick to send the stock spiraling downward.
In October, ALX reported a rare piece of positive news for drugs targeting CD47, the receptor at the heart of Gilead Sciences' cursed magrolimab program. The interim analysis covered 54 participants with HER2-positive gastric cancer who took either the CD47 blocker evorpacept or placebo on top of trastuzumab, Cyramza and paclitaxel. The response rates were 52% in the evorpacept arm and 22% in the control cohort.
ALX reported top-line data after the market closed Wednesday, revealing that the response rate in the evorpacept cohort fell to 40.3% in the final analysis. The control response rate rose to 26.6%. Talking on an ALX conference call to discuss the data, Jefferies analyst Michael Yee said the data show the response rates in patients who joined after the interim analysis were “very similar” between the two cohorts.
The result left ALX trying to explain how the 30 percentage point advantage over placebo seen in the first half of the trial evaporated in the second half of the study. Sophia Randolph, M.D., Ph.D., chief medical officer at ALX, cited two factors that differed between the patients treated before and after the interim analysis.
First, Randolph said the rate of patients enrolled using a fresh biopsy dropped from 46% in the first half of the trial to 32% in the second half of the trial. Having a fresh biopsy “can allow for the identification of a population enriched for HER2 expression,” Randolph said.
Second, the ALX exec said participants who enrolled in the evorpacept arm after the interim analysis “had characteristics suggestive of more aggressive disease, such as higher ECOG score, faster time to their first progression and overall just a shorter prior disease course.”
ALX CEO Jason Lettmann said the shift in the patient population “isn't a huge surprise when you put up data like we did at the interim.” Positive data can drum up interest in putting patients in a trial, and ALX “saw it in our enrollment and now we're seeing it in our data,” the CEO said. To Lettmann, “it's pretty clear that we have just a more aggressive patient population and we do think that's a significant factor.”
The readout included median durations of response (DOR) of 15.7 months in the evorpacept cohort and 7.6 months in the control arm. The progression-free survival (PFS) and overall survival data are immature. Lettmann said DOR “should correlate with PFS.”
ALX designed the study as a phase 2/3 study. The biotech plans to talk to the FDA before deciding on the next steps.
The company's stock was trading down 25% at $3.56 in premarket trading Thursday from a Wednesday closing price of $4.80.