Sylvester Cancer Center Tests Novel Virus-Immunotherapy Combination for Aggressive Neuroendocrine Tumors
核心洞察
Sylvester Comprehensive Cancer Center (搜索) has launched a phase I clinical trial combining oncolytic virus SVV-001 with checkpoint inhibitors nivolumab and ipilimumab for high-grade neuroendocrine tumors.
The trial has completed its first three dose levels with no severe treatment-related side effects reported, targeting patients whose tumors have become resistant to previous therapies.
Researchers identified tumor endothelial marker 8 (搜索) (TEM8 (搜索)) as a biomarker expressed only on cancer cells, which SVV-001 specifically targets to enhance immune recognition.
Sylvester Comprehensive Cancer Center (搜索) at the University of Miami Miller School of Medicine has opened enrollment for a groundbreaking phase I clinical trial testing a novel combination therapy for patients with high-grade neuroendocrine tumors. The study combines an oncolytic virus with immunotherapy drugs to target these aggressive cancers that have historically shown limited response to standard treatments.
Addressing an Unmet Medical Need
High-grade neuroendocrine cancer represents a complex and aggressive condition that has seen few medical advances, primarily due to its rarity limiting research investment. About one-sixth of neuroendocrine tumors are classified as high grade by pathologists, with survival rates varying by disease site but most patients succumbing within a year or two, according to Dr. Aman Chauhan, leader of the Neuroendocrine Tumor Program at Sylvester.
These tumors can originate from cells found throughout the body and affect most organ systems, most commonly attacking the lungs, gastrointestinal tract, gynecological tract, and prostate. While people older than 60 account for the majority of cases, these aggressive tumors can strike people of any age, as evidenced by victims including Sean Stone, a 26-year-old Hollywood producer, and Nichole Borchard, a 39-year-old mother of two.
Novel Therapeutic Approach
The trial, headed by Dr. Chauhan, employs a fresh approach combining checkpoint inhibitors nivolumab and ipilimumab with SVV-001 (Seneca Valley Virus-001), an oncolytic virus injected directly into tumors. This strategy addresses a key challenge in treating high-grade neuroendocrine carcinomas: very few respond to checkpoint inhibitors alone, though when they do, the effect is often long-lasting.
"Immunotherapy has revolutionized cancer treatment. But it still has a lot of issues, including resistance, and many patients are non-responders. This trial is about improving immunotherapy," explained Dr. Chinmay Jani, Sylvester chief fellow in hematology and oncology, who will present early findings at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.
Mechanism of Action
SVV-001 selectively targets cancer cells without infecting normal cells. The virus grows inside tumor cells and causes them to burst, releasing their contents and activating the immune system. This process creates a chain reaction as the virus continues to infect other tumors while the checkpoint inhibitors amplify the immune response against tumor components.
In preclinical cancer models tested by Chauhan and colleagues, this approach transformed immune "cold" tumors into "hot" tumors that respond to checkpoint inhibitors. The drugs acted like "fuel to the fire," strengthening the attack against the tumor, with results showing tumor shrinkage and durable responses.
Biomarker Discovery and Targeting
A significant advancement in this research is the identification of tumor endothelial marker 8 (搜索) (TEM8 (搜索)), a biomarker expressed exclusively on cancer cells. "There's no expression at all in normal organs such as lung, ovarian, pancreas, stomach, uterus, breast, colon, etc. However, in patients whose tumors express TEM8, the outcomes are poor. It increases tumor aggressiveness and metastasis as well," said Dr. Jani.
SVV-001's ability to target TEM8 (搜索) makes it a targeted immunotherapy drug, allowing for more precise attacks on aggressive cancer cells. Using next-generation sequencing, researchers will evaluate how TEM8 expression levels may influence patient outcomes.
Trial Design and Early Results
The phase I trial will enroll approximately 36 patients whose tumors have become resistant to or failed previous lines of therapy. The study officially launched in 2025 and has completed its first three dose levels, with participants receiving a single dose of SVV-001 followed by immunotherapy. No dose level tested to date has resulted in severe treatment-related side effects.
The trial's primary aim is to find safe combination doses and begin comparing effectiveness with historical data from standard-of-care treatment. In the next phase, participants will receive up to six doses of SVV-001 injections followed by immunotherapy, after which the study will expand at the optimal dose level.
Growing Research Program
Sylvester's neuroendocrine tumor program has attracted significant attention, with more than 550 new patients from 30 different states and 10 different countries seeking treatment and access to clinical trials in the past two years. This investigator-initiated trial represents Dr. Chauhan's first study at Sylvester dedicated specifically to high-grade neuroendocrine disease.
"Many tumors evade immune detection; this study evaluates whether SVV-001 can expose cancer cells and enhance the effectiveness of checkpoint inhibitors," said Dr. Gilberto Lopes, Sylvester's chief of medical oncology, associate director and medical director for international affairs.
The research reflects a growing effort at Sylvester to explore experimental therapeutics for cancers that have long lacked effective treatment options, offering cautious optimism rooted in science and collaboration for patients facing this aggressive disease.