FDA Grants Orphan Drug Designation to ELC-100 in Pancreatic NETs

Developers based the design of ELC-100 on the genetically modified adenovirus Ad5PTD, which they optimized to selectively infiltrate and replicate in NET cancer cells. As virus particles accumulate, developers hypothesize that the tumor cells may burst through immunogenic oncolysis, a process that can also activate the immune system.

The FDA has granted orphan drug designation to ELC-100 (AdVince), an investigational oncolytic virus, as a treatment for patients with pancreatic neuroendocrine tumors (NETs), according to a press release from the developer, Elicera Therapeutics, AB.¹

Investigators are currently evaluating the safety and maximum tolerated dose of ELC-100 among those with pancreatic NETs as part of a phase 1/2 trial (NCT02749331). Developers announced that the final patient had been recruited as part of this trial in October 2024.² Final data from the first part of this study are anticipated for release in mid-2025.

“[NETs] represent a highly heterogeneous indication and in our ongoing clinical study with patients [who are severely ill and] can be divided into several subgroups, including based on treatment history. This diversity highlights the need for new therapeutic solutions to be developed with a broad understanding of the specific needs of different patient groups,” Jamal El-Mosleh, chief executive officer at Elicera Therapeutics, stated in the press release.¹ “We are very pleased that ELC-100 has been granted orphan drug designation in the US. The decision by the FDA is a significant milestone in our efforts to develop a new form of treatment for patients with [NETs].”

Developers based the design of ELC-100 on the genetically modified adenovirus Ad5PTD, which they optimized to selectively infiltrate and replicate in NET cancer cells.³ As virus particles accumulate, developers hypothesize that the tumor cells may burst through immunogenic oncolysis, a process that can also activate the immune system.

Specifically, tumor cell death leads to the release of neoantigens that the patient’s antigen-presenting dendritic cells pick up, which triggers an immune response. This process may train T cells to attack cancer cells whenever they appear in the body. Developers hypothesize that ELC-100 may consequently produce a local tumor-killing effect in the injected disease while facilitating a long-term and systemic immune response via T-cell attacks on cancer cells and other parts of the body.

In the open-labelled, single-center phase 1/2a clinical study, investigators are assessing the safety of repeatedly infused ELC-100 among patients with metastatic NETs.⁴ In the dose-escalation portion of the study, patients will receive the investigational oncolytic virus at doses ranging from 10,000,000,000 to 1,000,000,000,000 virus particles.

The trial’s primary end point is the number of adverse effects (AEs) based on CTCAE v4.03 criteria. Secondary end points include changes in tumor size, changes in tumor metabolic activity, progression-free survival, changes in the replication profile of ELC-100, changes in the humoral response to ELC-100, and changes in the cytokine-mediated immune response.

Patients 18 to 100 years old with histologically and radiologically confirmed progressive neuroendocrine carcinoma of gastrointestinal, pancreatic, or bronchial origin harboring multiple liver metastases were eligible for enrollment on the trial. Other eligibility criteria included having patent portal vein and adequate liver perfusion, a Karnofsky performance status of at least 70%, a life expectancy of at least 6 months, and functioning NET with cover by somatostatin analog.

Those with known chronic liver dysfunction prior to the development of metastatic cancer or active infection were ineligible for enrollment on the study. Patients were also ineligible for enrollment if they had any viral syndrome diagnosed within 2 weeks of entry, chemotherapy within 4 weeks of beginning study treatment, radiotherapy to the target tumor site within the last 24 weeks of the baseline CT scan, a concomitant malignancy, or continuous therapy with any other anti-cancer treatment.

References

1. Elicera Therapeutics' drug candidate ELC-100 receives orphan drug designation in the U.S. for the treatment of pancreatic neuroendocrine tumors. News release. Elicera Therapeutics AB. January 13, 2025. Accessed January 13, 2025. https://tinyurl.com/yhbztjh2
2. Elicera Therapeutics enrolls the last patient in the clinical phase I/II-trial with oncolytic virus ELC-100. News release. Elicera Therapeutics AB. October 24, 2024. Accessed January 13, 2025. https://tinyurl.com/2hve5jbb
3. Pipeline. Elicera Therapeutics AB. Accessed January 15, 2025. https://tinyurl.com/46jpxx5b
4. Study of recombinant adenovirus AdVince in patients with neuroendocrine tumors; safety and efficacy (RADNET). ClinicalTrials.gov. Updated December 3, 2024. Accessed January 15, 2025. https://tinyurl.com/3dkemufc