Novel CD47 Inhibitor Shown Safe for Patients with HER2+ GEJ Cancer

ALX148, a CD47 inhibitor in combination with chemotherapy and trastuzumab (Herceptin) is a safe and well-tolerated treatment for patients with second-line or greater HER2-positive gastroesophageal junction (GEJ) cancer, according to a press release by ALX Oncology.¹

ALX148 is an inhibitor of CD47, a transmembrane anti-phagocytic protein within cancer cells. CD47 acts as a single to health cells to not destroy the cancer cell, by interacting with SIRPa, a regulatory membrane glycoprotein that can be found on the macrophages of other myeloid cells. This overexpression can lead to the immune system not being able to adapt and target these cancer cells.² 

The ongoing phase 1 ASPEN-01 (NCT03013218) study aims to test the efficacy of chemotherapy plus trastuzumab. The non-randomized, open-label study has an actual enrollment of 174 participants and an estimated completion date of December 2022. The primary end point of the study is dose-limiting toxicities.¹ 

The study was split into 6 arms. In arm 1, the dose-escalation arm, patients received ALX148 alone every week or every 2 weeks. In arm 2, patients received a combination of ALX148 plus pembrolizumab (Keytruda). In arm 3, patients received a combination of ALX148 and trastuzumab. In arm 4, patients received ALX148 and rituximab (Rituxan). In arm 5, patients received ALX148, 5-FU plus cisplatin chemotherapy, and pembrolizumab. In arm 6, patients received ALX148, plus trastuzumab, plus ramucirumab (Cyramza) plus paclitaxel (Taxol). 

In order to participate, patients must have a confirmed diagnosis of advanced or metastatic solid tumor malignancy or relapsed or refractory Non-Hodgkin lymphoma where no standard therapy is applicable, have adequate bone marrow, renal, and liver function, and adequate performance status. Patients with known central nervous system metastases or leptomeningeal disease requiring steroids, those who received high dose chemotherapy requiring stem cell rescue, or those who received prior CD47 treatment are not eligible to participate.

According to data presented at the 23rd World Congress on Gastrointestinal Cancer, 18 patients had been treated with either 10 mg/kg or 15 mg/kg of ALX148 once weekly with the dosing regimen of trastuzumab, ramucirumab, and paclitaxel. In patients with HER2-positive GEJ cancer who were on their second line or more of therapy, the overall response rate (ORR) was 72% and the 12-month overall survival (OS) was 76%. 

These results are consistent with prior randomized historical control studies such as RAINBOW (NCT01170663) which had an ORR of 28% and a 12-month OS of 40%, and DESTINY-01 (NCT03248492), which had an ORR of 41% and an OS at 12 months of 52%.

The maximum dose administered during the study was 15mg/kg once a week. However, preliminary data found that ALX148 may be combination with trastuzumab, ramucirumab, and paclitaxel with no maximum tolerated dose reached.

“The data that continue to emerge from this clinical trial are tremendously encouraging, suggesting that the combination of ALX148 with trastuzumab, ramucirumab, and paclitaxel may offer an important advancement for patients who have progressed on or after prior trastuzumab and chemotherapy,” said Hyun Cheol Chung, MD, Yonsei Cancer Center, South Korea, and an investigator for ASPEN-01, in a press release. “Importantly, these results also support ALX148’s tolerability profile, further differentiating it as a unique CD47 blocker that may be used in combination with an array of anti-cancer drugs, including chemotherapy.”

REFERENCES:

1. ALX Oncology announces new data from ASPEN-01, the phase 1b study of ALX148, showing robust objective response in patients with gastric or gastroesophageal junction cancer. News release. ALX Oncology. July 3, 2021. Accessed July 7, 2021. https://bit.ly/3yAdiI2.
2. CD47 is a Myeloid Checkpoint Target. ALX Oncology. Accessed July 7, 2021. https://bit.ly/3hMcN6X.