Just over a month after laying off staff to focus on its lead cancer candidate, ALX Oncology announced that the asset failed to meet the primary endpoints of two phase 2 trials and is scrapping further attempts in the indication as a result.
The CD47 inhibitor evorpacept, in combination with Merck & Co.’s Keytruda (pembrolizumab), failed to improve the objective response rate (ORR) in patients with advanced head and neck squamous cell carcinoma, ALX Oncology said in an April 25 release.
The Aspen-03 trial enrolled 189 patients and compared the combo to Keytruda alone, while Aspen-04 enrolled 172 patients and compared it to Keytruda plus chemotherapy.
“While there were encouraging trends in ASPEN-03 in ORR versus the historical and internal control, we've decided not to pursue evorpacept and pembrolizumab in head and neck cancer,” Alan Sandler, M.D., chief medical officer of ALX Oncology, said in the release. “We are disappointed that these studies did not meet their primary endpoints, most importantly for the patients for whom current standard-of-care treatment approaches fall short, and we thank all who participated in the trials.”
Despite the pair of new failed trials, the company remains committed to evorpacept.
“Based on the positive data and strong mechanistic rationale, we maintain our confidence in the evorpacept clinical development program and intend to deliver on that promise with additional clinical data in breast cancer and colorectal cancer in the near-term,” ALX Oncology CEO Jason Lettmann said in the release.
ALX Oncology is currently running a suite of other clinical trials testing evorpacept in combination with other therapies for numerous cancers, including breast cancer, multiple myeloma and urothelial cancer.
The Bay Area biotech shed 30% of its workforce and substantially slashed preclinical research in early March to funnel more cash toward evorpacept trials. ALX Oncology plans to launch new trials testing evorpacept with trastuzumab in HER2-positive breast cancer and with cetuximab in colorectal cancer, according to a March 5 release.
Those layoffs came about half a year after a full analysis of phase 2 gastric cancer data showed that evorpacept didn’t have as strong an effect as an interim analysis had suggested, causing ALX Oncology’s stock to tumble.
There are currently no approved drugs that target the CD47 receptor, a protein embedded in cell membranes that instructs macrophages not to destroy the cell. Cancer cells take advantage of CD47 to evade the immune system, so inhibiting the receptor’s activity could enable macrophages to see and destroy the malignant cells.
In one high-profile CD47 failure, Gilead Sciences spent $4.9 billion in 2020 to acquire Forty Seven and the biotech’s lead asset, the CD47 inhibiting antibody magrolimab. After years of failed trials, clinical holds from the FDA and even patient deaths, Gilead finally dumped magrolimab for good in August 2024.