ALX Oncology Holdings Inc. announced today that its investigational CD47-blocker evorpacept, when combined with Merck's Keytruda (pembrolizumab) with or without chemotherapy, failed to meet primary endpoints in two Phase 2 clinical trials for head and neck squamous cell carcinoma (HNSCC).
The ASPEN-03 and ASPEN-04 trials evaluated the combination therapy as a first-line treatment for patients with advanced HNSCC. Both studies failed to demonstrate improved objective response rates (ORRs) compared to historical controls of Keytruda alone and Keytruda with chemotherapy, respectively.
"While there were encouraging trends in ASPEN-03 in ORR versus the historical and internal control, we've decided not to pursue evorpacept and pembrolizumab in head and neck cancer in light of our prioritization of the more established anti-cancer antibody combination program based on multiple positive studies," said Dr. Alan Sandler, Chief Medical Officer at ALX Oncology.
Mechanism of Action and Safety Profile
Evorpacept blocks the 'don't eat me' signal transmitted by CD47 on cancer cell surfaces, which these cells use to evade immune system detection. The drug is uniquely designed to stimulate macrophages to selectively attack cancer cells when combined with active anti-cancer antibodies.
Despite the disappointing efficacy results, the combination demonstrated a manageable safety profile consistent with what has been previously reported for pembrolizumab and chemotherapy in this setting.
Shifting Focus to Other Cancer Types
While ALX Oncology will no longer pursue evorpacept in combination with pembrolizumab for HNSCC, the company remains confident in the drug's potential when combined with other anti-cancer antibodies.
"Moving forward, we are continuing to rapidly advance our clinical program combining evorpacept with anti-cancer antibodies supported by robust clinical data across trials in multiple tumor types," said Jason Lettmann, CEO at ALX Oncology. "Evorpacept has demonstrated response rates and durability beyond what is expected from standard of care across several studies when combined with Herceptin (trastuzumab), zanidatamab and Rituxan (rituximab)."
The company plans to continue evaluating evorpacept in combination with various anti-cancer antibodies in colorectal cancer, breast cancer, non-Hodgkin lymphoma, and multiple myeloma.
Trial Details
The ASPEN-03 trial enrolled 189 patients and evaluated evorpacept plus Keytruda versus Keytruda alone in patients with PD-L1 positive advanced, recurrent HNSCC who had not yet been treated for advanced cancer.
The ASPEN-04 trial enrolled 172 patients and studied evorpacept with Keytruda and chemotherapy in patients with metastatic or unresectable, recurrent HNSCC who had not yet received treatment for advanced disease.
Detailed findings from both trials will be submitted to a future medical meeting, according to ALX Oncology.
Regulatory Status and Future Development
The U.S. Food and Drug Administration (FDA) has previously granted both Fast Track designation and Orphan Drug designation to evorpacept for the second-line treatment of patients with HER2-positive gastric or gastroesophageal junction (GEJ) carcinoma.
ALX Oncology also continues development of ALX2004, its novel EGFR-targeted antibody-drug conjugate, which is anticipated to enter Phase 1 trials in mid-2025.
Head and Neck Cancer Burden
HNSCC is the seventh most common cancer worldwide, with incidence expected to increase 30% by 2030. Despite advancements in diagnosis and treatment, patients with HNSCC face a poor prognosis, particularly when diagnosed at advanced stages. The survival rate has only modestly improved in recent years, highlighting the continued need for improved therapeutics in this area.
