The Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, has opened enrollment for a groundbreaking clinical trial targeting patients with high-grade neuroendocrine tumors (NETs). Announced on April 9, 2025, this trial introduces a novel combination of immunotherapy and an oncolytic virus, offering new hope for a rare and aggressive cancer that has long defied significant medical progress.

High-grade neuroendocrine tumors arise from cells scattered throughout the body, capable of striking organs like the lungs, gastrointestinal tract, gynecological tract, and prostate.

About one-sixth of NETs are classified as high-grade, marked by their rapid growth and poor prognosis. Survival varies by tumor location, but most patients succumb within one to two years.

Historically, treatment options for high-grade NETs have been limited to conventional chemotherapy, which often yields disappointing results due to tumor resistance and severe side effects. The rarity of the disease has further stifled research investment, leaving patients with few alternatives—until now.

The new trial combines two cutting-edge therapies: checkpoint inhibitors and SVV-001, an oncolytic virus known as Seneca Valley Virus. Patients will receive the immunotherapy drugs nivolumab and ipilimumab, alongside direct injections of SVV-001 into their tumors, aiming to both destroy cancer cells and ignite a robust immune response.

Checkpoint inhibitors have revolutionized treatment for cancers like melanoma and lung cancer by blocking proteins that tumors use to evade the immune system. However, high-grade NETs rarely respond to these drugs alone, and when they do, only a small fraction of patients see lasting benefits. The challenge has been to make more tumors responsive—or “hot”—to immunotherapy.

SVV-001 virus selectively infects tumor cells, sparing healthy ones. Once inside, it multiplies and ruptures the cells, releasing their contents and alerting the immune system to the cancer’s presence. The virus then spreads to other tumor cells, perpetuating a chain reaction of destruction. This process turns immunologically “cold” tumors into “hot” ones, priming them for attack by the immune system, which the checkpoint inhibitors then amplify. Nivolumab and ipilimumab act like “fuel to the fire,” intensifying the immune assault on the tumor components exposed by SVV-001.

Preclinical studies conducted by Dr. Chauhan and his team demonstrated the potential of this approach, with tumors shrinking and showing durable responses in cancer models.

The virus’s ability to transform the tumor microenvironment, combined with the immune-boosting power of checkpoint inhibitors, offers a synergy not achievable with traditional therapies. Now, in this phase 1 trial, approximately 36 patients whose tumors have resisted prior treatments will test the combination’s safety and preliminary effectiveness, with results compared to historical standard-of-care data.
A unique feature of the trial is its focus on a biomarker called TEM8, found on tumor cells. SVV-001 binds to TEM8, enhancing its ability to target and infect cancer cells precisely. Testing for this biomarker could identify patients most likely to benefit, making the therapy a form of targeted immunotherapy.

Source.

Clinical trial.