Evorpacept Shows Promising Efficacy in HER2-Positive Gastric and GEJ Cancers

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Clinically meaningful improvements in overall response rate (ORR) and duration of response (DOR) were observed in patients with previously treated HER2-positive advanced gastric or gastroesophageal junction (GEJ) cancer who were treated with evorpacept (ALX148), a differentiated CD47 blocker, according to topline findings from the ASPEN-06 trial (NCT05002127).¹

In the intent-to-treat population of 127 patients with gastric or GEJ cancer, the ORR was 40.3% among patients treated with evorpacept plus trastuzumab (Herceptin), ramucirumab (Cyramza), and paclitaxel vs 26.6% for those given trastuzumab, ramucirumab, and paclitaxel alone. Of the 48 patients with fresh HER2-positive biopsies, the addition of evorpacept to trastuzumab, ramucirumab, and paclitaxel led to an ORR of 54.8% vs 23.1% in the control arm.

In the arm treated with the addition of evorpacept, the DOR was 15.7 months (95% CI, 11.0-not evaluable [NE]) vs 7.6 months in the control arm (95% CI, 6.3-NE). At the time of this analysis, the secondary end points of progression-free survival (PFS) and overall survival (OS) were immature.

“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 anticancer activity for patients with gastric cancers and continuing to surpass benchmarks in the field,” said Jason Lettmann, chief executive officer at ALX Oncology, in a press release. “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 anticancer antibodies in additional tumor types and drives ALX’s development strategy.”

The evorpacept, trastuzumab, ramucirumab, and paclitaxel combination was also generally well tolerated and consistent with data seen among those treated in the trastuzumab, ramucirumab, and paclitaxel control arm.

Previously, the FDA granted evorpacept a fast track designation for the second-line treatment of patients with HER2-positive gastric or GEJ carcinoma. The FDA and European Commission have also granted orphan drug designations to evorpacept for this indication.

Full data from the ASPEN-06 are expected to be submitted and presented at an upcoming medical meeting.

“By meeting our clinically meaningful and prespecified 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, MD, PhD, chief medical officer at ALX Oncology, in a press release. “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.”

About ASPEN-06

In the international, multicenter, randomized, ASPEN-06 trial, experts are exploring evorpacept when given in combination with trastuzumab, ramucirumab, and paclitaxel compared with trastuzumab, ramucirumab, and paclitaxel alone in patients with HER2-positive gastric or GEJ cancer. Patients were required to have received an anti-HER2 agent in prior lines of therapy; adequate bone marrow function, renal, and liver functions;and an adequate performance status.²

The study includes 2 experimental treatment arms and 2 comparator arms. Experimental arm A consisted of evorpacept 30 mg/kg twice weekly administered in combination with trastuzumab 6 mg/kg, ramucirumab 8 mg/kg, and paclitaxel 80 mg/m2 by intravenous (IV) infusion on days 1, 8, and 15 of a 28-day cycle. Arm A is being compared with arm B, which includes matching doses of trastuzumab, ramucirumab, and paclitaxel.

In the phase 3 experimental arm C, patients will receive the same doses of evorpacept, trastuzumab, ramucirumab, and paclitaxel. Arm C is being compared with the phase 3 arm B consisting of ramucirumab in combination with paclitaxel.

A total of 127 patients were enrolled, and the trial’s arms were generally well balanced based on prespecified stratification factors including line of therapy, prior fam-trastuzumab deruxtecan-nxki (Enhertu) use, Asia region, tumor location, HER2 expression level, and HER2-positive biopsy.

The primary end point of the trial is ORR. Secondary end points include median DOR, PFS, and OS.

REFERENCES:

1. ALX Oncology reports topline data from ASPEN-06 phase 2 trial demonstrating evorpacept improves tumor response in patients with HER2-positive gastric cancer. News release. ALX Oncology Holdings Inc. July 31, 2024. Accessed August 1, 2024. https://tinyurl.com/449hwceu

2. A study of evorpacept (ALX148) in patients with advanced HER2+ gastric cancer (ASPEN-06). Clinicaltrials.gov. Updated July 31, 2024. Accessed August 1, 2024. https://bit.ly/3J8rrCk