The VANCE trial, a multinational Phase III clinical trial, has concluded, marking a significant step in the development of precision T cell therapy for solid tumors. Led by researchers in Singapore, the trial demonstrated the feasibility of large-scale manufacturing and delivery of T cells across multiple international sites. The results, published in the Annals of Oncology, highlight the potential of T cell therapy while also revealing the need for further refinement to optimize patient outcomes.
The VANCE trial enrolled 330 patients with nasopharyngeal carcinoma (NPC) across 23 sites in Singapore, Malaysia, Thailand, Taiwan, and the United States between July 2014 and January 2020. Participants were randomized to receive either chemotherapy alone or chemotherapy followed by EBV-specific cytotoxic T cell (EBV-CTL) therapy. The EBV-CTL therapy involved administering over 1 billion precision-targeting T cells per patient over 6 cycles, following 4 cycles of chemotherapy (gemcitabine and carboplatin).
Trial Outcomes and Future Directions
The median overall survival for the entire cohort was 25 months in the chemotherapy plus EBV-CTL group and 24.9 months in the chemotherapy-only group, indicating no significant overall survival improvement. However, a subset analysis of patients from the US, Singapore, and Taiwan sites showed improved progression-free survival and overall survival in the group receiving the combined treatment. This suggests that specific patient populations may benefit more from this therapeutic approach.
"T cell therapies are not standardised but personalised and called a 'living therapy'," said Professor Toh Han Chong, lead investigator of the VANCE trial. "Our trial results indicate that more efforts are needed to improve how T cell therapies are developed and administered to optimise treatment outcomes for patients, and we have now started on these studies."
The Promise of EBV-CTL Therapy
NPC is closely associated with the Epstein-Barr virus (EBV), making it a suitable target for immunotherapy. Previous smaller studies have suggested that EBV-CTL therapy can produce clinical responses in NPC patients. A Phase II trial conducted at NCCS showed that adding EBV-CTL therapy after first-line chemotherapy resulted in a median survival of 29.9 months, compared to the historical median survival of 11 to 12 months with chemotherapy alone.
Next Steps: Biomarker Identification
Researchers are now focusing on identifying biomarkers in patient characteristics and the EBV-CTL therapy product to improve outcomes. A comprehensive analysis of the Phase II EBV-CTL trial will be presented at the European Society of Medical Oncology (ESMO) Asia Congress in December 2024. These results are crucial for validating biomarkers that will inform future VANCE trial biomarker studies.
"Adapted cell therapy by re-educating T cells against viral surface proteins is an effective and safe treatment," said Assistant Professor Jens Samol, Principal Investigator for the VANCE trial at TTSH. "The benefit to patients in an exploratory subgroup within the VANCE trial warrants further investigation and a comprehensive analysis of the Phase II EBV CTL trial may identify biomarkers to help this quest."
The VANCE trial represents a significant contribution to the field of T cell therapy for solid tumors, providing valuable insights into the challenges and opportunities of this approach. While the overall trial did not meet its primary endpoint, the subgroup analysis and ongoing biomarker studies offer hope for refining T cell therapy and improving outcomes for patients with NPC and potentially other EBV-associated malignancies.
