EMD Serono, the biopharmaceutical business of Merck (NYSE: MRK) KGaA, Darmstadt, Germany in the US and Canada, and Pfizer Inc. (NYSE: PFE) today announced the publication of detailed results from the Phase III JAVELIN Bladder 100 study online ahead of print in The New England Journal of Medicine. These results were published simultaneously with additional analyses being presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 and describe the efficacy of BAVENCIO® (avelumab) as a first-line maintenance treatment across various subgroups of patients with locally advanced or metastatic urothelial carcinoma (UC) and highlight exploratory biomarkers as well as patient-reported outcomes. In June, the US Food and Drug Administration (FDA) approved BAVENCIO for the maintenance treatment of patients with locally advanced or metastatic UC that has not progressed with first-line platinum-containing chemotherapy based on the JAVELIN Bladder 100 results.

In the JAVELIN Bladder 100 study, BAVENCIO plus best supportive care (BSC) significantly extended overall survival (OS) compared with BSC alone in the two primary populations of all randomized patients and patients whose tumors were PD-L1+, and significantly more patients who received BAVENCIO as first-line maintenance were alive at one year.1 The clinical benefits of BAVENCIO were seen across a range of patient populations.1,2

"These data, which supported the recent FDA approval and updates to NCCN and ESMO guidelines, establish that BAVENCIO first-line maintenance treatment could fundamentally change clinical practice for the treatment of patients with locally advanced or metastatic urothelial carcinoma," said Thomas Powles, MBBS, MRCP, MD, Professor of Genitourinary Oncology, Lead for Solid Tumour Research at Barts Cancer Institute, Queen Mary University of London, and Director of Barts Cancer Centre, London, UK. "It is notable that the longer overall survival with BAVENCIO maintenance therapy was observed across all pre-specified subgroups examined and that this prolonged overall survival was gained without a detrimental impact on patients' quality of life."

Primary AnalysisIn the JAVELIN Bladder 100 study, OS was significantly longer with BAVENCIO plus BSC compared to BSC alone in the primary population of all randomized patients (n=700) whose disease had not progressed on first-line platinum-containing chemotherapy:

• Median OS was 21.4 months (95% CI, 18.9 to 26.1) vs 14.3 months (95% CI, 12.9 to 17.9), respectively (HR 0.69; 95% CI, 0.56 to 0.86; P<0.001).1
• At one year, 71.3% of patients (95% CI, 66.0% to 76.0%) in the BAVENCIO arm were alive vs 58.4% (95% CI, 52.7% to 63.7%) of patients who received BSC alone.1

In the other primary population of patients with PD-L1+ tumors (n=358):

• OS was also significantly longer with BAVENCIO plus BSC vs BSC alone (HR 0.56; 95% CI, 0.40 to 0.79; P<0.001).1
• At one year, 79.1% (95% CI, 72.1% to 84.5%) of patients who received BAVENCIO were alive vs 60.4% (95% CI, 52.0% to 67.7%) in the BSC arm.1

All endpoints were measured from the time of randomization, after completion of four to six cycles of chemotherapy.

Subgroup AnalysisResults of an exploratory subgroup analysis show that consistent results were observed with the JAVELIN Bladder regimen of BAVENCIO first-line maintenance across pre-specified subgroups, including best response to first-line chemotherapy, type of chemotherapy regimen, site of baseline metastasis, and other baseline factors.1 In particular, hazard ratios for OS based on response to first-line chemotherapy were as follows:

• 0.69 for complete or partial response
• 0.70 for stable disease

With regard to first-line chemotherapy regimen, hazard ratios were as follows:

• 0.69 with gemcitabine plus cisplatin
• 0.66 with gemcitabine plus carboplatin

Further detail from the subgroup analysis were presented in an on-demand mini oral session at the meeting (Presentation #704MO). Additional data evaluating the association between clinical outcomes and exploratory biomarkers will be presented in the Proffered Paper 1 - GU, non prostate session on Saturday, September 19 (Presentation #699O), and patient-reported outcomes are featured in an on-demand e-poster display (Presentation #745P).

Safety No new safety signals were identified in the JAVELIN Bladder 100 study, and the safety profile was consistent with previous studies of BAVENCIO monotherapy.1 Treatment-related adverse events of grade 3 or higher occurred in 57 patients (16.6%) treated with BAVENCIO plus BSC; no grade 3 or higher treatment-related events occurred in the control arm.1 No grade 4 or fatal immune-related adverse events occurred.1 Investigators attributed two patient deaths in the BAVENCIO plus BSC arm (0.6%), due to sepsis and ischemic stroke, to study treatment toxicity.1