Biomarker analysis and updated clinical follow-up from BLASST-1 (Bladder Cancer Signal Seeking Trial) of nivolumab, gemcitabine, and cisplatin in patients with muscle-invasive bladder cancer (MIBC) undergoing cystectomy.
Authors: Shilpa Gupta, Ewan Gibb, Guru P. Sonpavde, Sumati Gupta, Benjamin L. Maughan, Neeraj Agarwal, Bradley Alexander McGregor, Christopher Weight, Xiao X. Wei, David Johnson Einstein, Christopher B. Dechet, Mark A. Preston, Matthew Mossanen, Bharat Thygarajan, Markus Eckstein, C. Marcela Diaz-Montero, Paari J. Murugan, Peter C. Black, Badrinath R. Konety
Journal: Journal of Clinical Oncology (2022)

528 Background: The BLASST-1 study is multi-center phase II trial evaluating the combination of nivolumab (N) with gemcitabine-cisplatin (GC) as a neoadjuvant therapy for patients (pts) with MIBC undergoing radical cystectomy (RC). The primary endpoint was pathologic down staging (PaR; ≤pT1N0). Safety, Relapse-free survival (RFS), Progression-free survival (PFS) and biomarker analyses were secondary endpoints. We previously reported a PaR rate of 65.8% and pCR rate of 49%. There were no safety concerns or delays to surgery. (ASCO GU 2020) Here, we correlate PaR with biomarkers (Tumor mutational burden (TMB), PD-L1 and molecular subtypes) and provide updated clinical follow-up (FU) data. Methods: Forty-one pts with MIBC (cT2-T4a, N≤1, M0) and candidates for RC were enrolled between Feb 2018 and June 2019; (cT2N0 90%, cT3N0 7%, cT4N1 3%). Pts received C (70mg/m2) IV on D1, G (1000mg/m2) on D1, D8 and N (360 mg) IV on D8 every 21 days for 4 cycles followed by RC within 8 weeks. For RNA-based analysis, GeneChip Human Exon 1.0 ST Array (Affymetrix) was used; baseline tumors from 37 patients passed quality control and had available transcriptome data. A cohort (n=223) of patients treated with NAC+RC was used as a comparator for molecular subtyping analysis. DNA was extracted from baseline pre-treatment tumor samples and sequenced to an average depth of 150X and the DNA extracted from matched normal tissue (peripheral blood) to a mean depth of 50X. PD-L1 expression was assessed using IHC 28-8 antibody on baseline tumors. Results: At a median FU of 15.8 months,12-month RFS rate was 85.4% and PFS including death from any cause was 83%. There were no long-term safety concerns. Molecular subtyping found patients with a basal-type tumor (Basal or Claudin-low) had a more favorable overall PaR in 13/18 = 73% with PaR in 9/13 in basal (69%) and 4/5 in claudin-low (80%) compared to overall PaR of 58% for the luminal-type tumors (Luminal or Infiltrated luminal) with a breakdown of PaR in 5/8 (63%) in luminal and 6/11 (54%) in infiltrated luminal. In contrast, in the comparator NAC cohort, the PaR rates were similar for basal-type and luminal-type tumors, with 44% and 48% respectively. There was no correlation of PaR with TMB or PD-L1 expression from bassline pre-treatment tumors. Biomarker analyses from residual tumors in RC tissues are ongoing. Conclusions: The combination of N+GC was safe and efficacious in MIBC with encouraging outcomes of pathologic down staging and relapse-free survival at a median FU of 15.8 months. Molecular subtyping results suggest basal-type tumors may respond more favorably to this chemo-immunotherapy treatment regimen. Clinical trial information: NCT03294304.