ALX Oncology's CD47 Inhibitor Fails in Head and Neck Cancer Trials, Company Pivots Strategy

ALX Oncology, a biopharmaceutical company focused on developing therapies that block the CD47 checkpoint pathway, announced disappointing results from two phase 2 clinical trials evaluating its lead candidate evorpacept in head and neck squamous cell carcinoma. Despite the setback, the company remains committed to the drug's development in other cancer indications.

Trial Results and Immediate Impact

The company reported that evorpacept, in combination with Merck & Co.'s Keytruda (pembrolizumab), failed to meet the primary endpoints in two separate phase 2 trials. The Aspen-03 trial, which enrolled 189 patients, compared the combination therapy to Keytruda alone, while the Aspen-04 trial, with 172 patients, evaluated the combination against Keytruda plus chemotherapy.

Dr. Alan Sandler, Chief Medical Officer of ALX Oncology, expressed disappointment in the results, stating, "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."

Strategic Pivot and Ongoing Development

Despite these setbacks, ALX Oncology is not abandoning evorpacept. CEO Jason Lettmann reaffirmed the company's commitment to the drug's clinical development program, citing "positive data and strong mechanistic rationale" in other indications. The company plans to focus on delivering additional clinical data in breast cancer and colorectal cancer in the near term.

ALX Oncology is currently conducting a suite of clinical trials testing evorpacept in combination with other therapies for various cancers, including breast cancer, multiple myeloma, and urothelial cancer. New trials are planned to evaluate evorpacept with trastuzumab in HER2-positive breast cancer and with cetuximab in colorectal cancer.

Broader Context and Industry Challenges

The failure of evorpacept in head and neck cancer trials highlights the ongoing challenges in developing effective CD47 inhibitors. This protein, embedded in cell membranes, acts as a "don't eat me" signal to macrophages, allowing cancer cells to evade the immune system. Despite the promising mechanism of action, no CD47-targeting drugs have yet gained regulatory approval.

The difficulties faced by ALX Oncology echo broader industry struggles with CD47 inhibitors. In a notable example, Gilead Sciences invested $4.9 billion to acquire Forty Seven Inc. and its CD47 inhibitor magrolimab in 2020. After years of setbacks, including failed trials, FDA clinical holds, and patient deaths, Gilead ultimately discontinued the development of magrolimab in August 2024.

As the pharmaceutical industry continues to explore the potential of CD47 inhibitors, ALX Oncology's strategic pivot underscores the importance of adaptability and perseverance in the face of clinical setbacks. The coming months will be crucial as the company seeks to demonstrate evorpacept's efficacy in other cancer indications, potentially reshaping the landscape of CD47-targeted therapies.