Evorpacept Plus Trastuzumab/Ramucirumab/Paclitaxel Improves ORR in Pretreated, Advanced HER2+ Gastric/GEJ Cancer

Second- or third-line treatment with the CD47 blocker evorpacept (ALX148) in combination with trastuzumab (Herceptin), ramucirumab (Cyramza), and paclitaxel improved responses vs trastuzumab/ramucirumab/paclitaxel alone in patients with HER2-positive, advanced gastric and gastroesophageal junction (GEJ) cancer, including those previously treated with fam-trastuzumab deruxtecan-nxki (Enhertu) and checkpoint inhibitor therapy, according to data from the phase 2 ASPEN-06 trial (NCT05002127).¹

Findings from a prespecified interim analysis showed that patients treated in the evorpacept arm experienced a confirmed overall response rate (ORR) of 52% vs 22% for patients treated with trastuzumab/ramucirumab/paclitaxel alone. The median duration of response was not reached in the investigational arm compared with 7.4 months for those treated with trastuzumab/ramucirumab/paclitaxel alone.

“The ASPEN-06 clinical trial validates the potential of evorpacept both in solid tumors and in combination with anticancer antibodies, and these data highlight the drug’s potential as a first-in-class foundational immunotherapy,” Sophia Randolph, MD, PhD, chief medical officer of ALX Oncology, stated in a news release. “We are highly encouraged by these initial randomized efficacy and safety results in [patients with] gastric cancer that build upon the activity previously seen in our first-in-human study and represent the first positive randomized clinical trial data presented for any CD47 blocker.”

ASPEN-06 is a randomized, multicenter, international, phase 2/3 trial enrolling patients at least 18 years of age with HER2-overexpressing advanced or metastatic gastric or GEJ adenocarcinoma whose disease has progressed on or after prior treatment with HER2-directed therapy and fluoropyrimidine- or platinum-containing chemotherapy.² Patients must also have adequate bone marrow, renal, and liver function, as well as adequate performance status.

Exclusion criteria for the study include those with known symptomatic central nervous system metastases or leptomeningeal disease requiring steroids; prior treatment with an anti-CD47 or anti-SIRPα agent; or prior treatment with ramucirumab.

In the phase 2, open-label portion of the study, patients enrolled thus far (n = 54) were randomly assigned to receive 30 mg/kg of intravenous (IV) evorpacept once every 2 weeks in combination with IV trastuzumab at an initial dose of 6 mg/kg followed by 4 mg/kg once every 2 weeks, IV ramucirumab at 8 mg/kg once every 2 weeks, and paclitaxel at 80 mg/m² on days 1, 8, and 15 of each 28-day cycle, or the same doses of trastuzumab plus ramucirumab and paclitaxel alone.

The phase 2 portion of the trial is designed to enroll 122 patients who meet the prespecified eligibility criteria. Pending data from the phase 2 portion of the trial to establish proof of concept, the phase 3 portion of the trial will then compare evorpacept plus trastuzumab, ramucirumab, and paclitaxel vs ramucirumab plus paclitaxel in a double-blind fashion.^1,2 Overall, approximately 450 patients are expected to be enrolled across both the phase 2 and 3 portions of the trials.²

ORR per RECIST v1.1 criteria is serving as the primary end point for phase 2. The primary end point of phase 3 will be overall survival.

Safety data for evorpacept were consistent with previous clinical trials, and the regimen was well-tolerated.¹

“ASPEN-06 is the first global randomized study in HER2-positive gastric cancer where prior [pembrolizumab] and [trastuzumab deruxtecan] were allowed,” Randolph continued. “We look forward to reporting the final analysis from the ongoing phase 2 ASPEN-06 study in 2024 and plan to initiate the phase 3 portion of ASPEN-06 in late 2024.”

References

1. ALX Oncology reports positive interim phase 2 ASPEN-06 clinical trial results of evorpacept for the treatment of advanced HER2-positive gastric cancer. News release. ALX Oncology. October 3, 2023. Accessed October 3, 2023. https://ir.alxoncology.com/node/8901/pdf
2. A study of evorpacept (ALX148) in patients with advanced HER2+ gastric cancer (ASPEN-06). ClinicalTrials.gov. Updated January 1, 2023. Accessed October 3, 2023. https://www.clinicaltrials.gov/study/NCT05002127