ALX Oncology released topline results from a Phase 2 gastric cancer trial, building on an interim readout from late last year that left a glimmer of hope alive for the CD47 space.
The experimental treatment, called evorpacept, achieved a 40.3% overall response rate when added to a three-drug standard-of-care regimen, compared to a 26.6% response rate against standard of care alone. CEO Jason Lettmann told Endpoints News that the study’s goal was an at least a 10-percentage-point difference, and that the result was statistically significant, with a p-value of p=0.027.
Patients in the active arm also saw a median 15.7-month duration of response, compared to 7.6 months in the control arm. Progression-free survival and overall survival figures were not mature at the time of ALX’s analysis.
But Wednesday’s results were less impressive than an interim readout from October 2023, which showed a 52% ORR in the active arm compared to 22% among standard-of-care patients.
“There’s a couple of different factors that may be at play, but the general take-home is that the second half of the study is probably a more aggressive population,” CMO Sophia Randolph said.
When patients were biopsied was also a factor, Randolph said, explaining that individuals who received a “fresh” biopsy — averaging one month before treatment — responded at a 54.8% rate in the active arm, compared with 23.1% in the control cohort. ALX enrolled 48 total patients in this subgroup.
Troubled class of drugs
ALX is charging ahead in CD47 despite the abundance of safety issues in the space, most notably with magrolimab, the lead program from the biotech Forty Seven that Gilead acquired in 2020. Concerns around the drug date back to early 2022, when the FDA ordered a clinical hold, and continued through last month when researchers at EHA reported a 20% increased risk of death compared to placebo. Gilead stopped all magrolimab studies in February.
Lettmann said ALX is taking a different approach toward CD47’s “don’t eat me” signal, which tells the immune system not to destroy cells, and that tumors can use to hide from the body’s defenses. Whereas magrolimab and other early CD47 drugs indiscriminately targeted the protein on both healthy and tumor cells, evoparcept contains a “silenced” component that helps direct it toward the cancer.
That silencing of what’s known as the Fc domain allows researchers to combine evoparcept with other established drugs, like Rituxan (CD20) and Herceptin (HER2). The trial ALX ran in gastric cancer aimed to see how much benefit evorpacept could provide on top of Herceptin, ramucirumab and paclitaxel.
Though that three-drug regimen is not the typical standard of care in this gastric cancer setting, Lettmann said the FDA wanted ALX to show just how much an effect evorpacept was providing. In the Phase 3 study, expected to begin before the end of 2024, ALX will test evorpacept, Herceptin, ramucirumab and paclitaxel compared to the more-typical ramucirumab and paclitaxel cocktail.
ALX has enough cash to continue running studies on its own, Lettmann said, but will look to raise money “when it makes sense.” In addition to gastric cancer, ALX is running two Phase 2 studies in head and neck cancer, looking at evorpacept in combination with Keytruda. Both are expected to read out topline results by the end of the first quarter of 2025.