Phase 1/2 ALT-100 Trial Targets the Bone Microenvironment in Metastatic Prostate Cancer

A newly registered Phase 1/2 clinical trial will investigate an unusual approach to treating metastatic prostate cancer: targeting the biological environment surrounding bone metastases rather than focusing exclusively on cancer cells.

The ALTAR-100 trial will evaluate ALT-100, an experimental monoclonal antibody. The study plans to enroll 42 patients with bone-predominant metastatic prostate cancer that has become resistant to androgen pathway-targeting treatments.

ALT-100 targets extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a protein involved in inflammatory signaling and interactions between tumor cells and their surroundings. Research suggests that eNAMPT can contribute to prostate cancer progression, particularly through pathways associated with inflammation and tissue remodeling.

One of the proposed mechanisms involves toll-like receptor 4 (TLR4), which participates in inflammatory signaling. Blocking the eNAMPT/TLR4 pathway could potentially interfere with conditions that help metastatic cancer survive and progress within bone tissue.

This is particularly relevant because bone is the most common site of metastatic prostate cancer. Cancer cells can exploit interactions with bone-forming cells, immune cells, and surrounding tissues, creating an environment that supports tumor growth and resistance to treatment.

The trial will administer ALT-100 intravenously every 28 days for up to six cycles, alongside continued androgen deprivation therapy.

Researchers will evaluate safety, PSA reductions of at least 30% and 50%, and radiographic progression-free survival. They will also measure inflammatory and bone-related biomarkers to investigate whether the antibody changes the metastatic microenvironment.

What makes ALT-100 particularly interesting is its therapeutic target. While most advanced prostate cancer treatments directly attack cancer cells or androgen signaling, ALT-100 attempts to disrupt the surrounding biological conditions that allow bone metastases to thrive.

If successful, this strategy could eventually provide a complementary approach to existing treatments, particularly for patients with bone-dominant disease.

Clinical trial