Matthew Galsky, MD
Results from the phase II CheckMate-275 trial demonstrated favorable safety and efficacy with the PD-1 inhibitor nivolumab (Opdivo) as a second-line treatment for patients with metastatic urothelial cancer who have progressed on first-line chemotherapy.
CheckMate-275 is the largest study of a PD-1 inhibitor in bladder cancer reported to date. Results showed that treatment with nivolumab was associated with a confirmed objective response rate of 19.6% (95% CI, 15.0-24.9),
“Most importantly, the responses were durable, as has been reported with other immune checkpoint inhibitors in other diseases,” lead study author Matthew Galsky, MD, said when presenting the findings at the 2016 ESMO Congress in October.
Based on the results of this trial, the FDA has granted a priority review designation to nivolumab as a treatment for patients with locally advanced unresectable or metastatic urothelial carcinoma following progression on a platinum-based regimen. The agency is expected to make a decision on the application by March 2, 2017.
In an interview with OncLive
, Galsky, a professor of Medicine at the Mount Sinai School of Medicine, provided an overview of the trial and discussed the significance of these novel findings.
OncLive: Could you provide an overview of CheckMate-275?
: Metastatic bladder cancer is treated in the first-line setting with chemotherapy, and chemotherapy has been the standard treatment for the past several decades. When patients progress on first-line chemotherapy, there really haven’t been any global standards of care in that patient population because no treatment has really been shown to have enough efficacy to become a standard of care for that patient population.
So it’s with that background that CheckMate-275 was designed, to determine whether or not immune checkpoint blockade in patients with disease progression, despite having chemotherapy, would be an effective strategy.
What were some of the major results of the trial?
Two hundred seventy patients were treated. The primary objective of the study was to define the objective response rate, which was determined by a blinded independent review committee. This study showed an objective response rate of 19.6%. Most importantly, the responses were durable, as has been reported with other immune checkpoint inhibitors in other diseases. The median duration of response has not been reached yet, with a median follow-up of 7 months.
Tumor PD-L1 expression did somewhat enrich for an increased likelihood of response. But even in patients with no tumor PD-L1 expression, the lower bound of the 95% confidence interval for response rate exceeded 10%, which was really the threshold set below which nivolumab would have been considered an improvement upon what’s been achieved historically with chemotherapy.
Are there any plans to test nivolumab in combination with other agents in this setting?
There are plans to explore nivolumab with multiple other agents. The combination furthest along is probably the one with ipilimumab (Yervoy), the CTLA-4 antibody. That’s being explored in a cohort of patients enrolled on the CheckMate-032 study. Many of those patients have already been enrolled, but that data has not been presented yet.
What do you expect the results to look like for that trial?
I anticipate that the results of the combination will be similar to what’s been seen in other tumor types—that there will be an increase in the response rate with combination therapy. Regarding the side effect profile of the combination regimen in this patient population, I think we’ll need to determine how that looks, to see if this is a viable strategy moving forward.
Were there any noteworthy toxicities associated with nivolumab?
Nivolumab, as an immune checkpoint inhibitor, can have immune-related toxicities associated with treatment. The rates of grade 3/4 treatment-related adverse events on this study were about 16%—so only a minority of patients have severe treatment-related side effects.