Evorpacept Plus TRP Yields Durable Responses in HER2+ Gastric/GEJ Cancer

Evorpacept (ALX148) plus trastuzumab (Herceptin), ramucirumab (Cyramza), and paclitaxel (TRP) generated clinically meaningful, robust, and durable responses with a tolerable safety profile in patients with previously treated HER2-positive gastric or gastroesophageal junction (GEJ) cancer, according to topline findings from the phase 2 ASPEN-06 trial (NCT05002127).¹

At a data cutoff of May 24, 2024, in the full intention-to-treat population (n = 127), evorpacept plus TRP (n = 63) elicited an overall response rate (ORR) of 40.3% vs 26.6% with TRP alone (n = 64; P = .027).² The median duration of response (DOR) was 15.7 months (95% CI, 11.0-not evaluable [NE]) in the evorpacept arm vs 7.6 months (95% CI, 6.3-NE) in the control arm.

The full dataset from ASPEN-06 will be submitted for presentation at a future medical meeting.¹

“This represents a couple big firsts,” Jason Lettmann, chief executive officer at ALX Oncology, stated in a conference call.² “They’re the first randomized data to read out in a prospective…clinical study in solid tumors in the CD47 space, and ASPEN-06 is the first randomized data ever to demonstrate both a tolerable safety profile and…a clear and durable improvement over standard of care.”

The randomized, multicenter, international ASPEN-06 trial evaluated the CD47 inhibitor evorpacept in combination with TRP vs TRP alone in patients with HER2-positive gastric/GEJ cancer who had previously received a HER2-directed agent in the first or second line. Patients were not permitted to have received prior treatment with an anti-CD47 agent, an anti-SIRP agent, or ramucirumab.² Patients who had received prior treatment with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) or checkpoint inhibitors were permitted to enroll.

Evorpacept was administered intravenously at 30 mg/kg every 2 weeks; trastuzumab was administered at a loading dose of 6 mg/kg followed by a dose of 4 mg/kg every 2 weeks; ramucirumab was administered at 8 mg/kg every 2 weeks; and paclitaxel was administered at 80 mg/m² on days 1, 8, and 15 of each 28-day cycle.

Patients were enrolled across 91 sites in 13 countries in Asia, Australia, Europe, and North America. Baseline characteristics, including line of therapy, prior T-DXd use, region of Asia, tumor location, HER2 expression level, and type of HER2-positive biopsy were generally well balanced between the 2 arms.

ORR served as the trial’s primary end point. Key secondary end points included safety, median DOR, progression-free survival (PFS), and overall survival (OS). PFS and OS data were immature at the time of this analysis.

In patients with fresh HER2-positive biopsies (n = 48), the evorpacept-based combination (n = 22) yielded an ORR of 54.8% vs 23.1% with TRP alone (n = 26; P = .0038).

“This improved benefit in this prespecified population of patients who are enriched for HER2 overexpression underscores the importance of this biomarker in [evorpacept plus] TRP response, and it continues to validate evorpacept’s mechanism of action,” Sophia Randolph, MD, PhD, chief medical officer at ALX Oncology, added in the conference call.

“There is substantial tumor shrinkage seen in patients who received [evorpacept plus] TRP compared with TRP,” Randolph noted. “[There is also a] relative greater depth of tumor shrinkage seen in the [evorpacept plus] TRP arm, supporting the contribution of evorpacept to that TRP backbone and the subsequent clinical benefit of the regimen seen in this trial.”

The evorpacept-based combination was generally well tolerated and was associated with a safety profile that was consistent with that of TRP alone. Among evaluable patients in the evorpacept arm (n = 63), the most common grade 3 or higher adverse effects (AEs) were decreased neutrophil counts (grade 3, 17.5%; grade 4, 11.1%), anemia (20.6%; 0%), neutropenia (17.5%; 4.8%), decreased white blood cell (WBC) counts (11.1%; 0%), hypertension (9.5%; 0%), sepsis (3.2%; 0%), asthenia (3.2%; 0%), and febrile neutropenia (1.6%; 0%). Additionally, 2 patients in this arm had grade 5 sepsis. Among evaluable patients in the TRP arm (n = 63), the most common grade 3 or higher AEs were decreased neutrophil counts (grade 3, 19.0%; grade 4, 6.3%), anemia (17.5%; 0%), neutropenia (11.1%; 1.6%), decreased WBC counts (9.5%; 0%), hypertension (6.3%; 0%), asthenia (6.3%; 0%), febrile neutropenia (3.2%; 3.2%), and sepsis (3.2%; 0%). Additionally, 1 patient in this arm had grade 5 sepsis.

No deaths related to the study treatment were observed on either arm.

“This is truly a novel immune-oncology agent that has the potential to be the first and best in class, and to see these data come through in a randomized study for the first time is very compelling,” Lettmann concluded.

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 July 31, 2024. https://ir.alxoncology.com/news-releases/news-release-details/alx-oncology-reports-topline-data-aspen-06-phase-2-trial
2. ALX Oncology Conference Call & Webcast. ALX Oncology. July 31, 2024. Accessed July 31, 2024.