The VOLGA trial: Exploratory analysis of plasma ctDNA

Prof Alexandra Drakaki, Medical Director of GU Oncology at UCLA, presented findings from the VOLGA trial, a phase 3 study focused on MIBC patients who are ineligible for cisplatin-based chemotherapy. The trial tested a neoadjuvant regimen of durvalumab, tremelimumab, and enfortumab vedotin (EV), followed by radical cystectomy, and 9 cycles of adjuvant therapy. ctDNA levels were measured from plasma samples using GRAIL’s cancer research solution to detect DNA methylation. These levels were assessed at baseline and after neoadjuvant therapy, evaluating their correlation with pathologic response and EFS.

The safety run-in cohort included 17 patients, all of whom received at least one cycle of neoadjuvant therapy. Thirteen patients completed all three cycles, and 14 underwent RC. At baseline, 63% of patients tested positive for ctDNA. After neoadjuvant treatment, over 79% of patients achieved ctDNA clearance. Among these, five patients had complete pathologic responses, and two showed stable disease at the time of surgery. Patients who cleared ctDNA exhibited prolonged EFS, while those who remained ctDNA-positive had poorer outcomes, including disease upstaging during surgery. 

This exploratory analysis of the VOLGA safety run-in cohort revealed that plasma ctDNA clearance during neoadjuvant treatment with durvalumab, tremelimumab and EV in MIBC patients may be linked to improved clinical outcomes. The association between ctDNA clearance and favourable responses suggests that ctDNA could serve as a potential surrogate marker for treatment efficacy. These promising findings will be further evaluated in the ongoing VOLGA trial to validate ctDNA as a predictive biomarker and explore its broader clinical significance.