On September 26, 2015, Genentech announced promising early results from a pivotal phase II study (IMvigor 210), which assessed the investigational cancer immunotherapy atezolizumab (anti-PDL1; MPDL3280A) in patients with locally advanced or mUC.
Clinicians may soon have a new tool for combating locally advanced or metastatic urothelial carcinoma (mUC).
On September 26, 2015, Genentech announced promising early results from a pivotal phase II study (IMvigor 210), which assessed the investigational cancer immunotherapy atezolizumab (anti-PDL1; MPDL3280A) in patients with locally advanced or mUC. The study showed that atezolizumab shrank tumors in 27% of mUC patients whose disease had medium and high levels of PD-L1 expression and worsened after initial treatment.
Atezolizumab is designed to target PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, atezolizumab may enable the activation of T cells.
“These results may represent the first major treatment advancement in advanced bladder cancer in nearly 30 years,” said Sandra Horning, MD, who is the chief medical officer and head of Global Product Development for Genentech in San Francisco in a press release. “We are encouraged that responses to atezolizumab were ongoing in the large majority of people when the study results were assessed.”
Results from the IMvigor study were presented at the European Cancer Conference in Vienna, Austria, September 25-29, 2015.
IMvigor 210 is an open-label, multicenter, single-arm phase II study that is evaluating the safety and efficacy of atezolizumab in patients with locally advanced or mUC, regardless of PD-L1 expression.
The investigators divided patients into 2 cohorts. Cohort 1 consisted of patients who had received no prior therapies for locally advanced or mUC, but who were ineligible for first-line cisplatin-based therapy. Cohort 2 included patients whose disease had progressed during or following previous treatment with a platinum-based chemotherapy regimen. Patients received a 1200 mg intravenous dose of atezolizumab on day one of 21-day cycles until progressive disease (cohort 1) or loss of clinical benefit (cohort 2).
Study results were evaluated according to the degree of PD-L1 expression on immune cells and on all comers showing significant overall response rate (ORR) improvements across all groups that increased with higher PD-L1 expression. ORR by RECIST 1.1 was 15% (P = .0058) in all comers, 18% (P = .0004) in immune cells 1/2/3 (PD-L1 expression ≥1%) compared to ORR 27% (P = .0001) in the immune cell 2/3 subgroup with PD-L1 expression ≥5%.
Although the median duration of response had not been reached at the time of the data cut-off, at a minimum follow-up of 24 weeks, 92% (43 of 47) of responding patients maintained response; 12 patients achieved complete response (CR), and 35 achieved partial response (PR). Progression-free survival at a median follow-up of 24 weeks was 2.1 months across all groups.
Safety was assessed in 311 patients and adverse events (AEs) were consistent with those observed in previous studies. The study showed that 15% of patients experienced grade 3/4 treatment-related AEs and 4% experienced a grade 3/4 immune-related adverse event. The most common grade 3/4 treatment related AEs were fatigue, decreased appetite, pyrexia, arthralgia, dyspnea, anemia, ALT increase, pneumonitis, hypertension, and hypotension.
Data will be submitted to the US Food and Drug Administration (FDA) under atezolizumab’s Breakthrough Therapy Designation for the treatment of patients whose metastatic bladder cancer expresses PD-L1.
Currently, Genentech has an ongoing randomized phase III study (IMvigor 211) comparing atezolizumab with standard-of-care chemotherapy in patients who have relapsed mUC. There also are 11 ongoing or planned phase III studies of atezolizumab across certain types of lung, kidney, breast, and bladder cancer.