Evorpacept

Evorpacept, also known by its development code ALX148, is an investigational substance with no marketing authorisation in the product records. It is a protein-based substance supplied as an injection for intravenous use, developed by ALX Oncology.^[1] It has received orphan designation in one product record, indicating it targets a rare disease.^[1]

What is evorpacept?

Evorpacept is a high-affinity CD47-blocking fusion protein with an inactive Fc region, designed to safely enhance standard anticancer therapeutics.^[6] It is an investigational substance, meaning it has not yet been authorised as a medicine. The substance is classified in the therapeutic area of neoplasms (cancers).^[1] It is known by the development code ALX148 and the name evorpacept.^[6]

How does evorpacept work?

CD47 is a "marker of self" that interacts with a protein called SIRPα on myeloid immune cells. Tumours upregulate CD47 to evade immune responses. Evorpacept blocks CD47, which may help the immune system recognise and attack cancer cells.^[6] It is designed to be combined with other anticancer treatments, such as pembrolizumab (a T cell checkpoint inhibitor) and chemotherapy, to potentially increase anti-tumour activity.^[6]

Which conditions is evorpacept studied for?

• Head and neck squamous cell carcinoma (HNSCC) — a cancer of the mouth, throat, or voice box that is metastatic (has spread) or cannot be removed by surgery.^[2][3]
• Gastric and gastroesophageal junction (GEJ) adenocarcinoma — a cancer of the stomach or the area where the stomach meets the oesophagus, specifically HER2-overexpressing tumours that have progressed after prior treatment.^[4]
• HER2-positive metastatic breast cancer — breast cancer that has spread and tests positive for the HER2 protein.^[5]
• Relapsed or refractory multiple myeloma (RRMM) — a cancer of plasma cells in the bone marrow that has returned after or not responded to treatment.^[1]

How is evorpacept given?

Evorpacept is given by intravenous infusion. In the trials, it is administered at a dose of 45 mg per kilogram of body weight in some studies.^[2][3] In other trials, the dose is not reported in the registry record.^[4][5]

What do the clinical trials show?

Five clinical trials of evorpacept are listed in the registries. They cover four different cancer types and range from Phase 1 to Phase 4. Two trials are completed, and three are authorised (meaning they have received regulatory approval to proceed but may not yet have started or finished).

What phases and status do the trials have?

• One Phase 1 trial in relapsed or refractory multiple myeloma, combining evorpacept with isatuximab and dexamethasone, is authorised.^[1]
• Two Phase 2 trials in head and neck squamous cell carcinoma, combining evorpacept with pembrolizumab (one also with chemotherapy), are completed.^[2][3]
• One Phase 2 trial in HER2-positive metastatic breast cancer, combining evorpacept with trastuzumab and single-agent chemotherapy, is authorised.^[5]
• One trial in gastric cancer includes Phase 2 and Phase 3 parts and is listed as Phase 4 in the registry; it is completed.^[4]

What are the trials measuring?

The trials primarily measure the objective response rate (ORR), which is the proportion of participants whose tumours shrink or disappear, assessed using RECIST version 1.1 criteria.^[2][3][5] The gastric cancer trial also measures overall survival (OS), the length of time participants live.^[4] The multiple myeloma trial measures the rate of very good partial response (VGPR) or better, as well as determining the recommended dose.^[1]

Who can take part in these trials?

Eligibility varies by trial. The HNSCC trials enrolled patients with metastatic or unresectable, recurrent disease who had not yet been treated for their advanced disease.^[2][3] The gastric cancer trial enrolled patients whose HER2-overexpressing cancer had progressed after prior HER2-directed therapy and chemotherapy.^[4] The breast cancer trial focuses on participants with CD47-positive, HER2-positive metastatic breast cancer.^[5] The multiple myeloma trial enrolled participants with relapsed or refractory disease.^[1]

What side effects are known?

The supplementary source reports that the combination of evorpacept with pembrolizumab and chemotherapy demonstrated "initial clinical response and tolerability" in the Phase 1 ASPEN-01 study, but does not provide a detailed list of side effects.^[6]