Evorpacept Combo Improves Responses in Pretreated HER2+ Gastric Cancer

Developers intend to submit detailed results from the ASPEN-06 trial (NCT05002127) for presentation at a future medical meeting.

Combination therapy with evorpacept (ALX148), trastuzumab (Herceptin), ramucirumab (Cyramza), and paclitaxel (TRP) meaningfully improved overall response rate (ORR) and duration of response (DOR) compared with TRP alone among those with previously treated HER2-positive advanced gastric cancer or gastroesophageal junction (GEJ) cancer, according to a press release on findings from the phase 2 ASPEN-06 trial (NCT05002127).¹

Across the entire intent-to-treat (ITT) population (n = 127), the ORR with evorpacept/TRP and TRP alone was 40.3% vs 26.6%, respectively. Additionally, the ORR in each respective arm was 54.8% vs 23.1% among patients with available HER2-positive biopsies (n = 48).

The median DOR with evorpacept plus TRP was 15.7 months (95% CI, 11.0-not evaluable [NE]) compared with 7.6 months (95% CI, 6.3-NE) in the TRP alone arm. Data related to progression-free survival (PFS) and overall survival (OS) were not yet mature at the time of the analysis. Investigators noted that treatment with evorpacept plus TRP was generally well tolerated and that its safety profile was comparable with that of TRP alone.

Developers intend to submit detailed results from ASPEN-06 for presentation at a future medical meeting.

“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,” Jason Lettmann, chief executive officer at ALX Oncology, said in the press release.¹ “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.”

In the multi-center, international, randomized ASPEN-06 trial, patients were assigned to receive trastuzumab, ramucirumab, and paclitaxel with or without evorpacept. Investigators administered trastuzumab at 6 mg/kg followed by 4 mg/kg every 2 weeks intravenously, ramucirumab at 8 mg/kg every 2 weeks intravenously, and paclitaxel at 80 mg/m² on days 1, 8, and 15 of each 28-day cycle.² Additionally, patients in the experimental arm of phase 2 received evorpacept at 30 mg/kg every 2 weeks intravenously.

The trial’s primary end point was ORR. Secondary end points included safety, DOR, PFS, and OS.

Patients 18 years and older with HER2-overexpressing advanced or metastatic gastric or GEJ adenocarcinoma and disease progression on or following prior anti-HER2 treatment plus fluoropyrimidine- or platinum-based chemotherapy were eligible for enrollment on the trial. Additional requirements for study entry included having adequate bone marrow function, adequate renal and liver function, and adequate performance status.

Those with symptomatic central nervous system (CNS) metastases or leptomeningeal disease requiring management with steroids were unable to enroll on the trial. Patients were also ineligible for enrollment if they had prior treatment with any anti-CD47 or anti- SIRPα agent or prior therapy with ramucirumab.

The FDA previously granted fast track designation to evorpacept as a second-line treatment for HER2-positive gastric or GEJ carcinoma in February 2020.³ The agency also gave fast track designation to the agent as a treatment for patients with head and neck squamous cell carcinoma at the same time.

“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,” Sophia Randolph, MD, PhD, chief medical officer at ALX Oncology, concluded.¹

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/ycyhjczd
2. A study of evorpacept (ALX148) in patients with advanced HER2+ gastric cancer (ASPEN-06). ClinicalTrials.gov. Accessed August 1, 2024. https://tinyurl.com/mw6mju5h
3. ALX Oncology’s ALX148 receives two fast track designations from FDA for the treatment of patients with head and neck squamous cell carcinoma and patients with gastric or gastroesophageal junction adenocarcinoma. News release. ALX Oncology Holdings Inc. February 18, 2020. Accessed August 1, 2024. https://tinyurl.com/mraku3j2