The VANCE trial, the largest clinical trial of T cell therapy for solid tumors to date, has concluded, signaling a potential shift towards precision immunotherapy. Led by researchers in Singapore, the multinational, Phase III VANCE trial assessed the efficacy of Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTL) therapy in 330 patients with advanced nasopharyngeal carcinoma (NPC). The study, published in the Annals of Oncology, demonstrated the feasibility of large-scale T cell therapy delivery but showed mixed results regarding overall survival.
Trial Design and Patient Population
The VANCE trial enrolled patients 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 (gemcitabine and carboplatin) followed by EBV-CTL therapy or chemotherapy alone. The EBV-CTL therapy involved six cycles, totaling over 1 billion T cells per patient, administered after chemotherapy completion. The primary endpoint was overall survival.
Overall Survival Results and Subset Analysis
While the median overall survival was similar between the two groups (25 months for chemotherapy plus EBV-CTL vs. 24.9 months for chemotherapy alone), a subset analysis of patients from US, Singapore, and Taiwan sites revealed improved progression-free survival and overall survival in the EBV-CTL therapy arm. This suggests that geographical or genetic factors may influence treatment response.
The Need for Precision in T Cell Therapy
Professor Toh Han Chong, lead investigator of the VANCE trial from the National Cancer Centre Singapore (NCCS), emphasized the personalized nature of T cell therapies. "Our trial results indicate that more efforts are needed to improve how T cell therapies are developed and administered to optimize treatment outcomes for patients, and we have now started on these studies," he stated.
The research team plans to focus on identifying biomarkers within patient immune systems and the EBV-CTL therapy product to refine patient selection and therapy design. Assistant Professor Jens Samol, Principal Investigator at Tan Tock Seng Hospital (TTSH), noted that the benefit observed in a subgroup of patients warrants further investigation. A comprehensive analysis of a Phase II EBV-CTL trial conducted at NCCS, identifying potential biomarkers, will be presented at the European Society of Medical Oncology (ESMO) Asia Congress in December 2024.
Implications for Nasopharyngeal Carcinoma Treatment
NPC is particularly prevalent in Southeast Asia and Southern China. While radiotherapy and chemoradiotherapy are effective for early-stage disease, treatment options for advanced NPC are limited, with median survival ranging from 21 to 29 months. The VANCE trial represents a significant effort to improve outcomes for these patients, even though the primary endpoint was not met in the overall cohort. The trial underscores the potential of T cell therapy in NPC, particularly with a more refined, precision-based approach.
