Dr McGregor on Future Biomarker Analyses With Nivolumab Plus Ipilimumab in Bladder Cancer

“Starting with this small trial of 19 patients [with bladder cancers], we found the signal of where the regimen seems to be effective, and then we took the next step. Now, as we work to publish the manuscript, we’re trying to look at biomarker response, including [in patients] with PD-L1 [expression]. We hope to have that analysis done [soon], so we can get these data out there.”

Bradley McGregor, MD, director, clinical research, Lank Center for Genitourinary Oncology; senior physician, Marra Lochiatto Investigator, Dana-Farber Cancer Institute (DFCI); assistant professor, medicine, Harvard Medical School, discusses data from an expansion cohort of a phase 2 study (NCT03333616)evaluating nivolumab (Opdivo) plus ipilimumab (Yervoy) for the treatment of patients with rare genitourinary (GU) malignancies, as well as next steps for this research in patients with diverse bladder cancer histologies.

The study, which was conducted through the DFCI rare GU tumor protocol, initially reported a 39% objective response rate (ORR) among 19 patients with bladder cancer with variant histologies who received nivolumab plus ipilimumab. In the expansion cohort, the ORR among the total population of patients with bladder cancer with variant histologies who received the combination (n = 49) was 37% (80% CI, 27%-47%). Moreover, the median duration of response was not yet reached, and 9 patients experienced a response lasting longer than 12 months at the data cutoff date. The median progression-free survival was 6.2 months (95% CI, 2.7-9.2), and the 12-month overall survival rate was 58% (95% CI, 42%-71%).

Building on these initial results, the researchers expanded the study to include patients with small cell carcinoma across the urinary tract or prostate, McGregor says. In this cohort, an approximate 50% ORR was observed, according to McGregor. Responses were either durable or followed by progression, with few instances of stable disease, he reports. The success in this initial expansion cohort led to further enrollment, resulting in a total of over 50 patients with divergent histologies of the urinary tract, McGregor says. The confirmed ORR in this larger cohort was approximately 40%, he says.

Starting with the small cohort of 19 patients with bladder cancers, McGregor and colleagues identified a promising signal for the regimen’s effectiveness. Accordingly, next steps for this research include conducting biomarker analyses, including PD-L1 expression, to further refine the understanding of response patterns, he explains. The expanded dataset, which includes approximately 50 patients with diverse histologies, represents one of the largest available subsets of patients for trial enrollment in this area, McGregor states. Results from this study are expected to provide valuable insights for guiding future therapy in this patient population, he concludes.