Data from the first-of-a-kind T cell therapy trial in Singapore for solid tumours show positive results, and represent a significant milestone, say experts.
“The delivery of high-quality T cells at large scale has been a major barrier for extending the applications of these therapies. To have achieved this goal when T cell therapy was in its infancy makes this Singapore-led achievement even more commendable,” said Professor Cliona Rooney, Baylor College of Medicine, America.
The study, published in Annals of Oncology, evaluated patients with nasopharyngeal (NPC) cancer. The phase 3 VANCE trial enrolled 330 patients, with 154 completing the study.
Notably, participants given the chemotherapy and EBV-specific cytotoxic T cell (EBV-CTL) therapy achieved better progression free survival and overall survival than those who received chemotherapy only.
A prior phase 2 trial showed benefit of giving T cell therapy after first line chemotherapy, reports the European Pharmarceutical Review, in which investigators reported a median survival of 29.9 months. Comparatively, in patients only given chemotherapy to historical trials, this was typically 11 to 12 months, the researchers had said.
One patient who attained complete disease clearance stayed alive for almost a decade, they added.
However, findings from this trial “indicate that more efforts are needed to improve how T cell therapies are developed and administered to optimise treatment outcomes for patients”, said VANCE trial lead and study first author, Professor Toh Han Chong, Senior Consultant, Division of Medical Oncology and Deputy Chief Executive Officer (Strategic Partnerships), National Cancer Centre Singapore (NCCS).
Cell therapy – opening a new era
As such, the solid tumour trial results suggest that identifying the patient biomarkers would boost positive outcomes with this type of therapy, facilitating precision delivery.
Analysis of the phase 2 EBV CTL trial identifying biomarkers will be presented at the European Society of Medical Oncology (ESMO) Asia Congress in December, the researchers confirmed.
Results from the phase 3 study were published in Annals of Oncology.
Study details
Gemcitabine, carboplatin, and Epstein–Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomised phase III trial
HC Toh, MM Yang, HM Wang et al.
Published in Annals of Oncology on 4 September 2024
Abstract
Background
Epstein–Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumour EBV-CTL activity and a favourable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment.
Patients and methods
This multicentre randomised, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomised to first-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety.
Results
A total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC + EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC + EBV-CTL subjects. The median OS was 25.0 months in the GC + EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% confidence interval 0.91-1.56; P = 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL.
Conclusions
GC + EBV-CTL in subjects with R/M NPC demonstrated a favourable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumours to date.
EPR article – Major immunotherapy trial sees survival benefit in solid tumours (Open access)
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