Dr Wainberg on the Phase 2/3 ASPEN-06 Study of Evorpacept in HER2-Overexpressing Gastric/GEJ Cancer

“The key efficacy data here are that the response rate was higher, numerically, and to some extent statistically higher, [with the 4-drug arm] compared with the 3-drug arm. Evorpacept plus trastuzumab, ramucirumab, and paclitaxel had a higher response rate compared with the 3-drug regimen.”

Zev A. Wainberg, MD, codirector, UCLA GI Oncology Program, and professor of medicine, UCLA Health, discusses findings from the phase 2/3 ASPEN-06 trial (NCT05002127) of evorpacept plus standard-of-care (SOC) trastuzumab (Herceptin), ramucirumab (Cyramza), and paclitaxel in HER2-overexpressing gastric/gastroesophageal junction (GEJ) cancer.

ASPEN-06 is a global study that enrolled patients with HER2-positive gastric or GEJ cancer who experienced disease progression on or after previous HER2-directed therapy. In order to be eligible, patients needed to be in the second or third line of treatment. Those who received prior fam-trastuzumab deruxtecan-nxki (Enhertu) and/or other checkpoint inhibitors were permitted. Those who received a prior CD47-agent, an anti-SIRPAα, or ramucirumab were excluded. Patients were randomly assigned 1:1 to receive evorpacept plus SOC trastuzumab, ramucirumab, and paclitaxel, or SOC therapy alone.

Findings from ASPEN-06 demonstrated that patients in the investigational arm (n = 63) experienced a confirmed overall response rate of 41.3% (95% CI, 29.0%-54.4%) vs 26.6% (95% CI, 16.3%-39.1%) in the control arm (n = 64), with 1 patient in each arm achieving a complete response. The median duration of response was 15.7 months (95% CI, 7.7-not reached [NR]) compared with 9.1 months (95% CI, 5.3-NR), respectively.

Although progression-free survival (PFS) data were still immature at the time of presentation, these findings demonstrated that the median PFS was 7.5 months (95% CI, 5.5-12.9) in the investigational arm compared with 7.4 months (95% CI, 4.6-9.0) in the SOC arm (HR, 0.77; 95% CI, 0.49-1.20). More time is needed to assess this end point conclusively, Wainberg says.