Phase II trial of atezolizumab plus chemotherapy after progression on single-agent PD-1 or PD-L1 inhibitor in cisplatin ineligible patients with advanced urothelial carcinoma HCRN GU17-295.

Abstract

TPS587 Background: Patients (pts) with cisplatin ineligible metastatic urothelial carcinoma (mUC) who progress after first-line PD1/PDL1 inhibition have limited treatment options. The concept of maintenance therapy with targeted agents and adding onto it at time of progression is a proven effective strategy. Preclinical data indicate that carboplatin+gemcitabine have immunomodulatory effect to potentially augment immune response. We hypothesize that in pts with cisplatin ineligible mUC, the use of atezolizumab+chemotherapy after progression on single-agent PD1/PDL1 inhibitor will result in clinical benefit. Methods: Multi-center, single arm, open label phase 2 trial of atezolizumab+carboplatin+gemcitabine in pts with cisplatin ineligible mUC. Eligible pts are adults with mUC (mixed histology allowed) who progressed after first line PD1/PDL1 inhibitor. Pts should be cisplatin ineligible based on consensus criteria. Neoadjuvant/adjuvant chemotherapy completed ≥12 months prior to enrollment is allowed. Treatment with atezolizumab will continue until disease progression or unacceptable toxicity while carboplatin+gemcitabine can be stopped after 4-6 cycles. Primary objective is progression-free survival per RECIST and secondary objectives are overall response rate, clinical benefit rate, and overall survival (OS). Exploratory endpoints include to compare OS of atezolizumab+carboplatin+gemcitabine in this trial compared to a virtual control arm of carboplatin+gemcitabine in mUC after progression on first-line PD1/PDL1 inhibitors. Other exploratory endpoints include to compare PD-L1 status at time of diagnosis and at time of enrollment (after progression on PD1/PDL1 inhibitor). Using an alternate hypothesis that atezolizumab+carboplatin+gemcitabine will have a median PFS of 9 months compared to historical control of 5 months with a platinum regimen in 2nd line setting, we plan to enroll 33 patients. This study is currently enrolling pts. A protocol amendment is under way that will allow pts with prior platinum-based chemotherapy to enroll on this trial. Clinical trial information: NCT03737123.