Treatment With Evorpacept Combination Initiates in ASPEN-06 Study for Gastric/GEJ Cancer

Following positive early results from the ASPEN-01 clinical trial, the first patient with HER2-positve gastric or gastroesophageal cancer has received the experimental combination of evorpacept, trastuzumab, ramucirumab, and paclitaxel in ASPEN-06.

Evorpacept in combination with trastuzumab (Herceptin), ramucirumab (Cyramza), and paclitaxel has been administered to the first patient enrolled in the phase 2/3 ASPEN-06 clinical trial, which is exploring the combination for the treatment of patients with HER2-positive gastric cancer or gastroesophageal junction (GEJ) cancer.1

“Patients with HER2-positive gastric/GEJ cancer are in need of tolerable and effective treatments, particularly in the second-line and later settings where resistance to HER2-directed therapy may have developed,” said Keun-Wook Lee, MD, PhD, professor of Seoul National University College of Medicine and director of Clinical Trials Center, Seoul National University Bundang Hospital, Seoul, Korea, in a press release. “Evorpacept’s favorable tolerability coupled with its novel approach of enhancing antibody dependent cellular phagocytosis engages the individual’s own innate anti-cancer immune response distinguishing it from other HER2-targeted approaches.”

Previously, response benefit was demonstrated with the evorpacept combination in patients with gastric cancer treated with the phase 1b ASPEN-01 clinical trial (NCT03013218). The gastric cancer cohort included 18 patients with HEr2-positive gastric cancer.1,2

According to preliminary findings presented during the Society of Immunotherapy for Cancer (SITC) Annual Meeting 2021, evorpacept in combination with trastuzumab, ramucirumab, and paclitaxel, achieved an objective response rate of 72.2% in the population of 18 patients with HER2-positive gastric cancer. The median overall survival (OS) observed with evorpacept was 17.1 months with a 12-month OS rate of 79%.2

The combination of evorpacept, trastuzumab, and ramucirumab was well-tolerated in the HER2-positive gastric cancer population. The majority of the treatment-related adverse events (AEs) observed in the cohort were low grade and infrequent.

The most common AEs observed with evorpacept, trastuzumab, and ramucirumab were epistaxis (50%), peripheral neuropathy (44%), decreased appetite (44%), and fatigue (39%). Twelve AEs were considered to be evorpacept-related and only 1 of them (lymphocyte count decreased) was grade 3 or higher.

In the ASPEN-06 study (NCT05002127), 450 patients with HER2-overexpressing advanced or metastatic gastric or GEJ adenocarcinoma that has progress on or after a prior HER2-directed agent as well as fluoropyrimidine or platinum-containing chemotherapy. All patients are required to have adequate bone marrow function, renal and liver function, and an adequate performance status. The study excludes individuals with known symptomatic central nervous system metastases or leptomeningeal disease requiring steroids. Patients who received prior treatment with an anti-CD47, anti-SIRPα agent, or ramucirumab are also excluded.3

The study will include 2 experimental treatment arms and 2 comparator arms. In the experimental arm A, evorpacept 30 mg/kg twice weekly will be 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 will be compared with arm B, which contains matching doses of trastuzumab, ramucirumab, and paclitaxel.

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

ASPEN-06 is actively recruiting patients with HER2-positive gastric and GEJ cancer at sites in California, Tennessee, Virginia, as well as in Asia and Europe.

“We are greatly encouraged by the exciting data that continue to emerge from ASPEN-01 and are pleased to announce the first patient dosed in ASPEN-06,” said Sophia Randolph, MD, PhD, chief medical pfficer, ALX Oncology, in the press release.1 “This milestone is an important step towards establishing evorpacept as a unique CD47 blocker that may be used in combination with other anti-cancer drugs for difficult-to-treat solid tumors, such as gastric/GEJ cancer, where more treatment options are desperately needed to improve disease outcomes.”

References:

1. 2. ALX Oncology announces first patient dosed in ASPEN-06, a phase 2/3 study of evorpacept for the treatment of patients with advanced gastric or gastroesophageal junction cancer. https://bit.ly/3KzrCa4

Lee K, Chung H, Lakhani N, et al. Evorpacept (ALX148), a CD46 myeloid checkpoint inhibitor, in patient with head and neck squamous cell carcinoma (HNSCC) and with gastric/gastroesophageal cancer (GC); ASPEN-01. Presented at the SITC 2021 Annual Meeting. November 10-14; Washington DC.

3. A study of evorpacept (ALX148) in patients with advanced HER2+ gastric cancer (ASPEN-06). Clinicaltrials.gov. Updated February 2, 2022. Accessed March 10, 2022. https://bit.ly/3J8rrCk