Approximately 40% of patients with MIBC are cisplatin-ineligible, and in this patient population, radical cystectomy (RC) alone remains the standard of care. VOLGA is the first international Phase 3 study examining the novel triplet combination of D (anti-PD-L1) + T (anti-CTLA-4) + EV (antibody–drug conjugate directed against nectin-4) for cisplatin-ineligible MIBC. Here, we present the safety run-in (SRI) results from VOLGA (NCT04960709).
Eligible patients were ≥18 yrs, cisplatin-ineligible (Galsky criteria), with histologically documented MIBC (urothelial and/or mixed) and clinical stage of T2-4aN0-N1M0 including T1N1M0. Treatment for the SRI population comprised 3 cycles of neoadjuvant therapy Q3W: D (1500 mg; Day 1 each cycle) + T (75 mg; Day 1, Cycle 1 and Day 8 Cycle 2) + EV (1.25 mg/kg; Days 1 & 8 each cycle), followed by radical cystectomy. In the adjuvant phase, patients receive 9 cycles of therapy Q4W: D (Day 1 each cycle) + T (Day 1, 1st cycle only). Primary SRI endpoints were safety and tolerability. Data cutoff was August 2022.
A total of 17 patients participated in the SRI (see Table). All 3 neoadjuvant cycles were completed by 13 patients. Radical cystectomy was performed in 14 patients, with no delays in time to surgery. Overall, 16 patients experienced ≥1 treatment-related AE (TRAE): 8 patients had Grade 3 or 4 TRAEs, and no Grade 5 TRAEs occurred. Disease progression occurred in 1 patient prior to cystectomy and in 1 patient post-surgery. Further safety and efficacy for the SRI population will be presented.
| Baseline Characteristics (N=17) | n (%) |
| Age | Median: 75 years; Range: 50-83 |
| Male | 16 (94) |
|
ECOG Performance Status |
8 (47) 8 (47) 1 (6) |
| Tumor Stage T2 T2a T2b T3 T4a Regional Lymph Nodes N0 N1 Metastases M0 |
7 (41) 3 (18) 3 (18) 2 (12) 2 (12) 15 (88) 2 (12) 17 (100) |
Preliminary safety results from the SRI portion of the VOLGA trial support continued evaluation of the triplet regimen of D+T+EV in patients with cisplatin-ineligible MIBC. The randomized phase 3 portion of VOLGA has opened for enrollment, with a recent protocol amendment to also include patients who refuse cisplatin.