A pilot pre-surgical study evaluating anti-PD-L1 durvalumab (durva) plus anti-CTLA-4 tremelimumab (treme) in patients with muscle-Invasive, high-risk urothelial bladder carcinoma who are ineligible for cisplatin-based neoadjuvant chemotherapy.

Abstract

e16524 Background: In patients with muscle-invasive bladder cancer (MIBC), especially those with high risk features including lymphovascular invasion, hydronephrosis, T3b disease, or variant histology, cisplatin-based neoadjuvant chemotherapy followed by cystectomy improves overall survival as compared to cystectomy alone. However, it is estimated that over 50% of patients with MIBC are ineligible for cisplatin-containing therapy. Therefore, we propose to use durva plus treme as neoadjuvant therapy for this population of patients. Methods: We carried out a single-arm, pre-surgical clinical trial with durva + treme in patients with localized, high-risk MIBC who are ineligible for cisplatin-containing chemotherapy due to decreased renal function, neuropathy, hearing loss, or heart failure (NCT02812420). Each patient will receive durva (1500 mg) plus treme (75 mg) on weeks 1 and 5. Patients will then undergo surgery at week 9-11. Pre- and post-treatment blood and tumor samples will be collected for immunological and genomic analyses for clinical correlation. Results: Twelve patients have been enrolled on this trial. Six patients have completed cystectomy as of January 30, 2018. Of these 6 patients, 3 (50%) had pathologically complete response (pCR); one (17%) did not respond; two (33%) had upstaging of disease. Of the two upstaged patients, one was found to have tumor progression in a pre-existing pelvic lymph node and was taken off trial, treated with chemotherapy, then had cystectomy with pCR. Only 1 of 12 patients developed grade 3 immune related toxicity. Immunologic and molecular analyses are ongoing on all collected samples. Conclusions: To date, out data indicate that durva plus treme may be an effective and well tolerated neoadjuvant therapy for patients with MIBC ineligible for cisplatin-based therapy. Based upon these data, we have expand this pilot trial from 15 to 35 patients. We will also report correlative biomarker data. Clinical trial information: NCT02812420.