ASPEN-06 Phase 2 Final Analysis Demonstrates Benefit of ALX148 Combination for Gastric Cancer

At the American Society of Clinical Oncology 2025 Gastrointestinal Cancers Symposium, Kohei Shitara, MD, presented the results of a final analysis on the randomized phase 2 portion of the ASPEN-06 trial. ASPEN-06 was a phase II/III study that analyzed the use of the CD47 myeloid checkpoint inhibitor ALX148 (evorpacept) in patients with HER2-overexpressing gastric/gastroesophageal cancer (GC).

ALX148 is being studied across various forms of cancer in combination with anticancer antibodies and checkpoint inhibitors for its ability to safely magnify anticancer antibody-dependent cellular phagocytosis.

The ASPEN-06 randomized phase II trial evaluated ALX148 in combination with trastuzumab, ramucirumab, and paclitaxel (TRP) for the treatment of patients with HER2-positive GC. The study involved patients with second- or third-line HER2-positive advanced or metastatic GC that progressed on or after prior anti-HER2 therapy.

A total of 127 patients were randomized to receive either ALX148, 30 mg/kg, every 2 weeks with TRP or TRP alone. The patients’ most recent GC tissue sample was used to determine HER2 status. The primary objectives of the study were to compare the confirmed overall response rate (ORR) of ALX148 plus TRP with the assumed ORR of ramucirumab and paclitaxel (=30%) with one-sided alpha error of 0.025 and to determine if ALX148 provides a clinically meaningful contribution to TRP in ORR (delta>10%).

The ORR of the patient population was 40.3% with ALX148 plus TRP and 26.6% with TRP alone. Although the difference in ORR between ALX148 plus TRP and the historical ORRs of ramucirumab and paclitaxel was not statistically significant (P=.095), the ORR of ALX148 plus TRP showed a meaningful delta of 13.7% over the ORR of TRP alone (P=.028 in an exploratory analysis).

The median duration of response (DOR) of ALX148 plus TRP and TRP alone was 15.7 and 7.6 months, respectively. In a study of a prespecified population of 48 patients with HER2-positive disease in fresh tumor tissues after previous anti-HER2 treatment, the ORR of ALX148 plus TRP (54.8%) was favorable in comparison with the historical ORR of ramucirumab and paclitaxel (P=.030) with a delta of 31.7% over TRP’s ORR of 23.1% (P=.004 in an exploratory analysis).

The use of ALX148 plus TRP in patients with HER2-positive GC demonstrated a safety profile consistent with prior evaluation, with a higher beneficial response in tumors identified as HER2-positive when fresh biopsy specimens were used. These data suggest the importance of obtaining biopsy specimens after anti-HER2 therapy. The results of this study support the ongoing investigation into this combination as an adjunct to anti-HER2 GC therapy.