ALX Oncology (ALXO) Study Update summary

Study design and patient selection

• ASPEN-06 is a global, randomized phase II study evaluating evorpacept plus trastuzumab, ramucirumab, and paclitaxel (TRP) in HER2-positive advanced/metastatic gastric or GEJ cancer patients who progressed after prior HER2 therapy.

• Patients were enrolled based on HER2 positivity confirmed by fresh or archival biopsy or ctDNA, with both methods prespecified in the statistical analysis plan and ctDNA analysis as an exploratory endpoint.

• The study included 127 patients (63 in the evorpacept arm, 64 in control), with balanced demographics and prior treatment exposure.

• Primary endpoints were overall response rate (ORR) in ITT and fresh HER2-positive biopsy populations; secondary endpoints included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

• Fresh biopsy and ctDNA were used to confirm HER2 status, enriching for patients most likely to benefit.

Efficacy and safety results

• In the ITT population, evorpacept plus TRP achieved a confirmed ORR of 41.3% vs 26.6% for TRP alone, with a median DOR of 15.7 vs 9.1 months.

• In HER2-confirmed (fresh biopsy or ctDNA) patients, ORR was 48.9% for evorpacept + TRP vs 24.5% for TRP; median DOR was 15.7 vs 9.1 months; median PFS was 7.5 vs 6.7 months, with a PFS HR of 0.64.

• Fresh HER2-positive biopsy patients saw a 59% ORR with evorpacept + TRP vs 23% for TRP.

• Efficacy was observed even in patients who had progressed on prior HER2-targeted therapies, including trastuzumab and Enhertu.

• Safety profile was favorable and consistent with prior experience, with grade ≥3 adverse events largely balanced between arms and no new safety signals.

Biomarker-driven and mechanistic insights

• Confirmed HER2 positivity by fresh biopsy or ctDNA identified patients with higher response rates and longer DOR.

• ctDNA analysis revealed that about one-third of archival biopsy patients were not truly HER2 positive, explaining lower response rates in that group.

• Evorpacept is a differentiated CD47 inhibitor with an inactive Fc domain, requiring combination with Fc-active antibodies for optimal effect and engaging the innate immune system.

• Durable responses and late separation of PFS curves are consistent with immune-oncology mechanisms.