ALX Oncology (ALXO) Study Result summary

Study Overview and Design

• ASPEN-06 is a randomized, multi-center, international phase II trial evaluating evorpacept (a CD47 blocker) in combination with trastuzumab, ramucirumab, and paclitaxel (TRP) versus TRP alone in HER2-positive gastric or gastroesophageal junction (GEJ) cancer patients who progressed after anti-HER2 therapy.

• 127 patients were randomized 1:1 to receive evorpacept + TRP or TRP alone, with primary endpoint of overall response rate (ORR) and secondary endpoints including duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

• The study enrolled patients across 13 countries and over 90 sites, with robust stratification by cancer type, biopsy timing, region, treatment line, and HER2 status.

• Both archival and fresh HER2-positive biopsies were included, with a focus on the impact of recent HER2 expression.

• The trial reflects global standards of care and included a balanced geographic distribution.

Mechanism of Action and Rationale

• Evorpacept is a differentiated CD47 blocker designed to enhance macrophage-mediated phagocytosis of cancer cells while minimizing toxicity to healthy cells.

• Its inactive Fc domain and high-affinity CD47 binding allow for targeted blockade, reducing off-target effects and enabling higher dosing.

• Combining evorpacept with trastuzumab leverages HER2 expression to drive antibody-dependent cellular phagocytosis, with HER2 positivity serving as a key biomarker for response.

• The benefit is consistent with evorpacept’s mechanism, requiring both CD47 blockade and HER2-driven antibody activity.

• Evorpacept’s design enables combination with various anti-cancer agents.

Key Efficacy Results

• In the intent-to-treat population, evorpacept + TRP achieved a confirmed ORR of 40.3% versus 26.6% for TRP alone (p=0.027), with a median DOR of 15.7 months compared to 7.6 months for control.

• Among patients with fresh HER2-positive biopsies, ORR was 54.8% for evorpacept + TRP versus 23.1% for TRP (p=0.0038), highlighting the importance of recent HER2 expression.

• Evorpacept provided deeper and more durable tumor shrinkage, especially in the fresh biopsy subgroup.

• The benefit was observed regardless of HER2 IHC score or prior anti-HER2/checkpoint inhibitor use.

• Secondary endpoints of PFS and OS were immature at the time of analysis.