New Clinical Trial for High-Grade Neuroendocrine Tumors Opens at Sylvester
A Phase 1 trial is now open to test a novel combination of two immunotherapy drugs and a tumor-injectable oncolytic virus in patients whose high-grade neuroendocrine tumors have failed previous therapies.
Trial Leadership and Location
The trial is led by Dr. Aman Chauhan, who heads the Neuroendocrine Tumor Program at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine. This is Dr. Chauhan's first investigator-initiated trial at Sylvester dedicated specifically to high-grade neuroendocrine disease.
Trial Design and Eligibility
The study is a Phase 1 trial designed to enroll approximately 36 participants. Eligible patients are those whose high-grade neuroendocrine tumors have become resistant to or have failed previous lines of therapy.
The primary aim of the trial is to determine safe combination doses of the investigational treatment. A secondary aim is to begin comparing the treatment's effectiveness with historical data from standard-of-care therapies.
Investigational Treatment
Patients in the trial will receive a combination therapy consisting of:
- Two immunotherapy drugs, nivolumab and ipilimumab, which are checkpoint inhibitors.
- An oncolytic virus called SVV-001 (Seneca Valley Virus-001), which will be injected directly into tumors.
Scientific Rationale: Checkpoint inhibitors have broadened treatment options for a growing list of tumor types, but very few high-grade neuroendocrine carcinomas respond to them. SVV-001 is an oncolytic virus that does not infect normal cells but grows inside tumor cells, causing them to burst. This releases tumor contents, which can activate the immune system. The virus can then go on to infect other tumors.
According to Dr. Chauhan, preclinical studies showed this combination caused tumors to shrink and yielded durable responses. In those models, the oncolytic virus was observed turning immune "cold" tumors into "hot" tumors that are more responsive to checkpoint inhibitors.
Patient Selection Biomarker
Tumors from patients enrolled in the trial will be tested for the presence of a biomarker called TEM8. This biomarker binds to the oncolytic virus SVV-001, allowing it to attach to and infect cancer cells.
Background on High-Grade Neuroendocrine Cancer
- Neuroendocrine tumors originate from cells found throughout the body and can affect most organ systems, most commonly the lungs, gastrointestinal tract, gynecological tract, and prostate.
- Approximately one-sixth of neuroendocrine tumors are classified as high grade.
- According to Dr. Chauhan, survival rates for high-grade neuroendocrine cancer vary with the site of the disease, but most patients succumb within one to two years.
- People older than 60 account for the majority of cases, but these tumors can occur at any age.
- Conventional chemotherapy is a current treatment option.
Additional Context
- In the past two years, more than 550 new patients from 30 different U.S. states and 10 different countries have come to Sylvester for treatment and access to neuroendocrine cancer clinical trials.
- Dr. Chauhan heads several clinical trials for neuroendocrine tumors and carcinomas.
- Research at Sylvester is supported by fundraising entities established by families of patients who died from high-grade neuroendocrine disease, including Sean Stone's Neuroendocrine Carcinoma Fundraiser and the Nichole Borchard Foundation.