Merck/Pfizer's Bavencio Shows Significant Overall Survival Benefit as First-Line Maintenance Therapy in Advanced Urothelial Carcinoma in Phase III Trial

Bavencio is an immuno-oncology drug co-developed by Pfizer and Merck, approved in the United States in May 2017FDAAccelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC), specifically: (1) patients who have disease progression during or following platinum-containing chemotherapy; (2) patients who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This approval is based onTumorRemission Data and Duration of Remission.

The JAVELIN Bladder 100 study is a confirmatory Phase III trial designed to support the conversion of Bavencio’s indication for urothelial carcinoma (UC) from accelerated approval to full approval. In April this year, based on positive interim analysis results from this study, Pfizer and Merck submitted a supplemental Biologics License Application (sBLA) to the U.S. FDA for the use of Bavencio as first-line maintenance therapy in patients with locally advanced or metastatic UC. Meanwhile, the FDA has granted Breakthrough Therapy Designation (BTD) to Bavencio for this indication, and the sBLA is currently underFDABased on real-timeTumorReview of the Real-World Evidence (RWE) Pilot Project.

Bladder Cancer - (Image source: medscape.com)

JAVELIN Bladder 100 is a multicenter, multinational, randomized, open-label, parallel-group study conducted in patients with locally advanced or metastatic urothelial carcinoma (UC) who did not experience disease progression after first-line platinum-based chemotherapy, to evaluate the efficacy and safety of Bavencio in combination with best supportive care (BSC) versus BSC alone as first-line maintenance therapy. In the study, a total of 700 patients who did not experience disease progression after induction chemotherapy (as assessed by RECIST v1.1) were randomly assigned to either the Bavencio plus BSC group or the BSC group. The primary endpoint was in all randomized patients and PD-L1-positiveTumorOverall Survival (OS) in Patients.

In this study, BSC will be administered at the discretion of the treating physician and may includeAntibioticsTreatment, nutritional support, correction of metabolic disorders, optimization of symptom control and pain management (including palliative radiotherapy), etc. BSC does not include any active anti-TumorTreatment, but local radiotherapy for isolated lesions is acceptable.

The results showed that at the interim analysis, the study had reached the primary endpoint of overall survival (OS): in two co-primary populations (all randomized patients and patients with PD-L1-positive tumors), Bavencio plus best supportive care (BSC) achieved a statistically significant improvement in OS compared to BSC alone. Specifically, among all randomized patients, the median OS was significantly prolonged in the Bavencio plus BSC group compared to the BSC group (21.4 months vs. 14.3 months), with a 31% reduction in the risk of death (HR=0.69; 95% CI: 0.56–0.86; p<0.001). The 12-month survival rates (71% vs. 58%) and 18-month survival rates (61% vs. 44%) were also substantially improved. In PD-L1-positiveTumorAmong patients, Bavencio + BSC demonstrated greater OS benefit compared with BSC alone, reducing the risk of death by 44%. In this study, the safety profile of Bavencio was consistent with that observed in the JAVELIN monotherapy clinical development program.

According to the study, Bavencio is the firstClinical TrialImmunotherapy that achieved a statistically significant improvement in overall survival as first-line treatment for advanced urothelial carcinoma in China.For the past 30 years, chemotherapy has been the standard of care as first-line treatment for patients with advanced urothelial carcinoma. Although it is an effective short-term option for many patients, most eventually experience disease progression, highlighting the need for additional therapeutic options. Based on the positive overall survival (OS) results from the JAVELIN Bladder 100 study, Bavencio has the potential to change clinical practice.

Globally, bladder cancer is the tenth most common cancer. In 2018, there were over 500,000 newly diagnosed cases of bladder cancer worldwide, and approximately 200,000 people died from the disease. Urothelial carcinoma (UC) accounts for about 90% of bladder cancers. When bladder cancer metastasizes, the 5-year survival rate is only 5%. Combination chemotherapy is currently the first-line standard of care for advanced disease; however, although initial response rates are high, durable and complete responses after first-line chemotherapy are uncommon, with most patients ultimately experiencing disease progression within 9 months of initiating treatment. Given the poor prognosis and disease progression in patients with advanced bladder cancer following first-line chemotherapy, there is an urgent need for additional therapeutic options to improve overall survival.

Bavencio belongs to the class of PD-(L)1 tumor immunotherapies, a highly regarded category of cancer treatments that harnesses the body’s own immune system to fight cancer by blocking the PD-1/PD-L1 signaling pathway, thereby inducing cancer cell death and demonstrating potential for treating various types of tumors. Bavencio has been shown in preclinical models to engage both adaptive and innate immune responses. By blocking the interaction between PD-L1 and the PD-1 receptor, Bavencio has been demonstrated in preclinical models to release T cell-mediated anti-TumorInhibitory Effect on Immune Response.

In November 2014, Pfizer entered into an agreement worth up to $2.85 billion with Merck KGaA to enter the PD-(L)1 field. Currently, both parties are advancing the JAVELIN clinical development program, which involves more than 15 different types of tumors and over 10,000 patients. In addition to gastric/gastroesophageal junction adenocarcinoma, theseTumorTypes also include: ovarian cancer,Breast Cancer, head and neck cancer, Merkel cell carcinoma, non-small cell lung cancer, renal cell carcinoma, and urothelial carcinoma.

In the United States, Bavencio was approved in March 2017FDAAccelerated approval for the treatment of metastatic Merkel cell carcinoma (mMCC) in pediatric patients aged 12 years and older and adults, making this drug the first globally approved therapy for mMCC.TumorImmunotherapy, a type of therapy that is moreMelanomaAggressive skin cancers with a poorer prognosis. In May 2017, Bavencio received accelerated approval from the U.S. FDA for: (1) patients with locally advanced or metastatic urothelial carcinoma (mUC) who experienced disease progression during or after platinum-containing chemotherapy; and (2) patients with locally advanced or metastatic urothelial carcinoma (mUC) who experienced disease progression within 12 months after receiving platinum-containing chemotherapy in the neoadjuvant (pre-surgical) or adjuvant (post-surgical) setting. In May 2019, the combination therapy of Bavencio and the tyrosine kinase inhibitor Inlyta (axitinib) was approvedFDAApproved for the first-line treatment of patients with advanced renal cell carcinoma (RCC). (Bioon.com)

Original Source: The bladder cancer pendulum swings towards Bavencio