ALX Oncology: ASPEN-06 Phase 2 Trial Shows Evorpacept Boosts Tumor Response in HER2-Positive Gastric Cancer

ALX Oncology Holdings Inc. has announced promising results from its Phase 2 ASPEN-06 clinical trial evaluating evorpacept for the treatment of HER2-positive advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer. Evorpacept, a CD47-blocking therapeutic developed by the company, aims to inhibit the CD47 immune checkpoint pathway, thus enhancing the body’s immune response against cancer cells.

The Phase 2 ASPEN-06 trial is a randomized, multi-center, international study comparing the efficacy of evorpacept in combination with trastuzumab, CYRAMZA® (ramucirumab), and paclitaxel (collectively referred to as TRP) against the TRP regimen alone. A total of 127 patients participated in the trial, all of whom had received prior anti-HER2 therapy. The primary endpoint of the study was overall response rate (ORR), with key secondary endpoints including safety, median duration of response (mDOR), progression-free survival (PFS), and overall survival (OS).

In the full intent-to-treat population, the combination of evorpacept and TRP achieved an ORR of 40.3%, compared to 26.6% for the control group receiving TRP alone. In a subset of patients with fresh HER2-positive biopsies, the benefits were even more pronounced, with an ORR of 54.8% versus 23.1% for the control group. The median duration of response was notably longer in the evorpacept arm, at 15.7 months, compared to 7.6 months for the control group. Secondary endpoints of PFS and OS were immature at the time of the interim analysis.

“Evorpacept has demonstrated a clinically meaningful impact on key measures of anti-cancer activity for patients with gastric cancers,” said Jason Lettmann, CEO of ALX Oncology. “These results provide valuable insights beyond the interim data previously reported and identify the most responsive patient population. The clinical benefit seen in this trial supports the development of evorpacept in combination with anti-cancer antibodies in additional tumor types.”

The trial was well-balanced across different arms based on pre-specified stratification factors, including line of therapy, prior ENHERTU® (fam-trastuzumab deruxtecan-nxki) use, geographical region, tumor location, HER2 expression level, and the type of HER2-positive biopsy.

Evorpacept has shown a well-tolerated safety profile, with adverse events consistent with those observed in the control group. This makes evorpacept the first CD47 blocker to show durable clinical benefit and a well-tolerated safety profile in a prospective randomized trial.

“The data validate the mechanism of action and potential clinical utility of evorpacept for patients,” stated Dr. Sophia Randolph, Chief Medical Officer at ALX Oncology. “ASPEN-06 also provides valuable insights into responding patient populations and the importance of HER2 target expression that will inform our clinical program.”

The trial’s full data set will be presented at an upcoming medical conference. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to evorpacept for the second-line treatment of patients with HER2-positive gastric or GEJ carcinoma. Additionally, both the FDA and the European Commission have granted Orphan Drug Designation for this indication.

ALX Oncology is committed to advancing its pipeline of immuno-oncology therapies, focusing on combining evorpacept with anti-cancer antibodies, antibody-drug conjugates, and PD-1/PD-L1 immune checkpoint inhibitors. Evorpacept’s design, featuring an inactive Fc effector function, has demonstrated a superior safety profile compared to other anti-CD47 molecules, allowing for higher dosages with minimal overlapping toxicity. By blocking the CD47 signal, evorpacept enables the immune system's macrophages and dendritic cells to more effectively target and destroy cancer cells.

The clinical advancements of evorpacept represent a significant milestone in the treatment of HER2-positive gastric and GEJ cancers, offering new hope for patients battling these challenging diseases.

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