Bavencio Meets Primary Endpoint in Bladder Cancer Trial

By Rajaneesh K. Gopinath, Ph.D.

Urothelial Carcinoma – The Disease and Existing Treatments

Urothelial carcinoma (UC) accounts for 90% of all bladder cancers and is the most common type found in the United States. It is characterized by the growth of cancer on the urothelium, the highly-specialized, inner epithelium lining of the urinary bladder. Advanced or metastatic stages of UC are difficult to treat and patients have a very low survival rate. For a long time, such patients were commonly treated with first-line combination chemotherapy regimens comprising of gemcitabine and cisplatin (GC) or methotrexate, vinblastine, adriamycin, and cisplatin (MVAC). However, the arrival of immune checkpoint inhibitors and a kinase inhibitor has improved the therapeutic landscape of UC significantly. The following drugs were FDA approved for the second-line treatment of platinum-refractory, advanced or metastatic UC (see table below).

In June 2018, the FDA changed the prescribing label for Atezolizumab and Pembrolizumab following new data from ongoing trials. Based on that, the use of both drugs was limited to the first-line treatment for metastatic bladder cancer in patients who can’t receive cisplatin-based chemotherapy and have high levels of PD-L1. However, a number of phase III trials testing combination therapies of Atezolizumab for the treatment of advanced or metastatic UC are currently underway.

History of Bavencio

Bavencio is a human IgG1, anti-PD-L1 monoclonal antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. In May 2017, it was FDA approved for the treatment of patients with locally advanced or metastatic UC who have disease progression during or following platinum-containing chemotherapy. The approval was based on the phase I JAVELIN Solid Tumor trial that included 242 patients with that indication. The drug is also FDA approved for other indications. In March 2017, Bavencio received FDA approval for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel-cell carcinoma (MCC). Last year, in May it was approved in combination with Axitinib for the first-line treatment of patients with advanced renal cell carcinoma.

Recent Success in Phase III UC Trial

Two days ago, Merck KGaA (EMD Serono in the US and Canada) and Pfizer announced the interim analysis of their phase III JAVELIN Bladder 100 study conducted in patients with previously untreated locally advanced or metastatic UC. The analysis shows that the study met its primary endpoint of overall survival (OS). Results demonstrate that the patients who were randomized to receive first-line maintenance therapy with Avelumab and best supportive care (BSC) lived significantly longer than those with BSC only. The safety profile of the drug was consistent with that in the JAVELIN monotherapy clinical development program that involves over 10,000 patients evaluated across more than 15 different tumor types. The results will be presented at an upcoming medical congress and shared with the FDA and other health authorities.

“Bavencio is the first immunotherapy to demonstrate in a clinical trial a statistically significant improvement in overall survival as a first-line treatment for patients with advanced urothelial carcinoma,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “These latest positive data from the JAVELIN clinical development program add to the body of evidence for Bavencio in the treatment of genitourinary cancers, and we look forward to discussing these results with health authorities.”

References

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452591/
2. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-limits-use-tecentriq-and-keytruda-some-urothelial-cancer-patients
3. https://www.pfizer.com/news/press-release/press-release-detail/fda_grants_bavencio_avelumab_approval_for_a_common_type_of_advanced_bladder_cancer
4. https://www.pfizer.com/news/press-release/press-release-detail/fda_grants_approval_for_bavencio_avelumab_the_first_immunotherapy_approved_for_metastatic_merkel_cell_carcinoma
5. https://www.pfizer.com/news/press-release/press-release-detail/fda_approves_bavencio_avelumab_plus_inlyta_axitinib_combination_for_patients_with_advanced_renal_cell_carcinoma
6. https://www.pfizer.com/news/press-release/press-release-detail/bavencio_significantly_improved_overall_survival_in_patients_with_locally_advanced_or_metastatic_urothelial_carcinoma

Author

Rajaneesh K. Gopinath