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ALX Oncology’s CD47-blocker evorpacept, in combination with MSD’s blockbuster Keytruda (pembrolizumab), has failed to show benefit in two Phase II trials.
The combination was being investigated in the ASPEN-03 (NCT04675294) and ASPEN-04 (NCT04675333) clinical trials as a first-line treatment for patients with advanced head and neck squamous cell carcinoma (HNSCC).
ALX said the combination did not improve objective response rates (ORR) compared to historical controls of Keytruda alone or Keytruda with chemotherapy.
As a result, the company will no longer pursue evorpacept in combination with Keytruda in HNSCC, with ALX to now focus on trials investigating evorpacept with other anti-cancer antibodies, including Cyramza (ramucirumab), Herceptin (trastuzumab), Rituxan (rituximab) and Ziihera (zanidatamab).
The company’s Nasdaq-listed stock fell 9.8% on 25 April 2025, dropping from $0.601 at Thursday’s close to $0.542.
ALX Oncology CEO Jason Lettmann said: "Based on the positive data and strong mechanistic rationale, we maintain our confidence in the evorpacept clinical development programme and intend to deliver on that promise with additional clinical data in breast cancer and colorectal cancer in the near-term.
"With evorpacept and ALX2004, our novel EGFR-targeted antibody-drug conjugate, we continue our commitment to bringing forth meaningful therapies for patients living with cancer."
Despite the efficacy failure, the combination demonstrated a manageable safety profile consistent Keytruda and chemotherapy in the same patient population.
ALX said more detailed data from the two studies will be submitted to a future medical meeting.
CD47 inhibition mechanism under microscope
Evorpacept acts by blocking CD47, a molecule commonly found on the surface of many cancers that acts as a “don't eat me signal”, allowing them to invade immune cells such as macrophages. By inhibiting CD47, evorpacept helps trigger anti-tumour activity.
This marks another bump in the road for ALX after it downsized staffing by 30% and slashed preclinical research within the company in March 2025 to redirect funding to trials of evorpacept. Last year, the company’s stock fell after full Phase II data from a Phase II study of the drug in gastric cancer data were not as strong as an interim analysis had suggested.
CD47 inhibition has also struggled as a mechanism of action, with no CD47 drugs yet approved. Gilead has stopped the development of a CD47 inhibitor, magrolimab, which it obtained during a $4.9bn acquisition of Forty Seven in 2020 after a string of trial failures and clinical holds by the US Food and Drug Administration (FDA).