On July 31, 2024 ALX Oncology Holdings Inc., ("ALX Oncology" or the "Company") (Nasdaq: ALXO), an immuno-oncology company developing therapies that block the CD47 immune checkpoint pathway, reported topline data from its Phase 2 ASPEN-06 clinical trial (Press release, ALX Oncology, JUL 31, 2024, View Source [SID1234645197]). The trial demonstrated clinically meaningful improvements in overall response rate and duration of response among patients with previously treated HER2-positive advanced gastric cancer (GC) or gastroesophageal junction (GEJ) cancer.

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"The topline results from the ASPEN-06 clinical trial confirm the robust response that evorpacept can deliver, generating a clinically meaningful impact on key measures of anti-cancer activity for patients with gastric cancers and continuing to surpass benchmarks in the field," said Jason Lettmann, chief executive officer at ALX Oncology. "Additionally, they provide valuable insight beyond the interim data previously reported, offering a more conclusive look at the impact of evorpacept and identifying the most responsive patient population. Importantly, the level of clinical benefit seen in this trial provides support for developing evorpacept in combination with anti-cancer antibodies in additional tumor types and drives ALX’s development strategy."

ASPEN-06 is a randomized, multi-center, international trial evaluating evorpacept, ALX Oncology’s investigational CD47-blocking therapeutic that uniquely combines a high-affinity CD47-binding domain with an inactivated proprietary Fc domain, in combination with trastuzumab, CYRAMZA (ramucirumab) and paclitaxel (collectively, TRP) against TRP alone for the treatment of patients with HER2-positive gastric/GEJ cancer, where all patients had received an anti-HER2 agent in prior lines of therapy. Patients in the trial (N=127) were generally well-balanced across arms based on pre-specified stratification factors including line of therapy, prior ENHERTU (fam-trastuzumab deruxtecan-nxki) use, Asia region, tumor location (GC or GEJ), HER2 expression level (IHC3+ or IHC2+/ISH+) and HER2-positive biopsy (fresh or archival).

The trial’s primary endpoint is overall response rate (ORR). Key secondary endpoints are safety, median duration of response (mDOR), progression-free survival (PFS) and overall survival (OS).

Key Phase 2 ASPEN-06 Clinical Trial Topline Results:

In the full intent-to-treat population (N=127), the addition of evorpacept to TRP demonstrated an ORR of 40.3% compared to the TRP control ORR of 26.6%
In patients with fresh HER2-positive biopsies (n=48), evorpacept plus TRP demonstrated an ORR of 54.8% compared to 23.1% for the TRP control
Median duration of response (DOR) in the evorpacept arm was 15.7 months [95% CI: 11.0; NE] compared to the TRP control of 7.6 months [95% CI: 6.3; NE] in the full intent-to-treat population
Secondary endpoints of PFS and OS were immature at the time of analysis
Evorpacept in combination with TRP was generally well tolerated and consistent with TRP control
"By meeting our clinically meaningful and pre-specified threshold of greater than 10% difference in response between the evorpacept treatment and control arms, these new data validate the mechanism of action and potential clinical utility of evorpacept for patients. Notably, this is now the first CD47 blocker to demonstrate clinical benefit and a well-tolerated safety profile in a randomized trial," said Sophia Randolph, M.D., Ph.D., 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. These data represent a significant advancement for immuno-oncology."

The ASPEN-06 full data set will be submitted for presentation 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 European Commission have granted Orphan Drug Designation for this indication.

Conference Call and Webcast on July 31 at 4:30 PM EDT
The Company will host a conference call and webcast today at 4:30 PM EDT. To access the live conference call, please dial (800) 715-9871 (U.S./Canada) or +44.800.260.6466 (internationally) at least 10 minutes prior to the start time and refer to conference ID 9637001. The link to the live webcast of the conference call will be posted in the News & Events section (see "Events") of the Company’s website at www.alxoncology.com. An archived replay will be accessible for 90 days following the event.

About the ASPEN-06 Phase 2 Clinical Trial
ASPEN-06 is a randomized Phase 2 (open-label) / Phase 3 (double-blinded), multi-center, international trial of patients with second- or third-line metastatic HER2-overexpressing gastric/GEJ adenocarcinoma that progressed on or after prior HER2-directed therapy and fluoropyrimidine- or platinum-containing chemotherapy (NCT05002127). HER2 status was determined by an FDA-approved test in the most recent gastric/GEJ cancer tissue sample. The primary analysis of the full intent-to-treat population included all randomized patients whose HER2 status was based on a tissue sample obtained at any time. An additional primary analysis was conducted on patients who had a recent HER2-positive tissue sample after prior anti-HER2 therapy ("fresh biopsy"). While trastuzumab is currently approved in combination with cisplatin and capecitabine/5-FU for HER2-positive gastric/GEJ cancers, it is not approved in combination with standard-of-care CYRAMZA + paclitaxel. The Phase 2 portion of the ASPEN-06 trial enrolled 127 patients. To determine the activity of evorpacept + trastuzumab + CYRAMZA + paclitaxel, in the Phase 2 portion of ASPEN-06, patients were randomized to receive either a four-drug combination regimen (evorpacept + trastuzumab + CYRAMZA + paclitaxel) or a three-drug combination regimen (trastuzumab + CYRAMZA + paclitaxel). This design enabled the assessment of evorpacept’s contribution to the standard of care plus trastuzumab and to global standard of care, CYRAMZA + paclitaxel.