Bladder Cancer Breakthrough: EU CHMP Recommends Approval of Merck/Pfizer Immunotherapy Bavencio for First-Line Maintenance Treatment

December 14, 2020 /BioonBIOON/ -- Merck KGaA and its partnersPfizer(Pfizer) recently announced jointly that the European Commission (EC) has issued a positive review opinion, recommending the approval of the anti-PD-L1 therapy Bavencio (avelumab) as a monotherapy for first-line maintenance treatment in adult patients with locally advanced or metastatic urothelial carcinoma (UC) whose disease has not progressed after first-line platinum-based chemotherapy. The CHMP’s opinion will now be submitted to the European Commission (EC) for review, which is expected to make a final decision in early 2021.

Bavencio is an immuneTumorstudied pharmacy, and obtained a degree 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 receiving platinum-containing chemotherapy in the neoadjuvant or adjuvant setting.

In June this year, based on the results of the confirmatory Phase 3 JAVELIN Bladder 100 study, the United StatesFDAApproval Granted to Convert Bavencio’s Indication for UC from Accelerated Approval to Full Approval: For Maintenance Treatment in Patients with Locally Advanced or Metastatic UC Who Have Not Experienced Disease Progression Following First-Line Platinum-Containing Chemotherapy. Currently, the aforementioned indication for Bavencio is also under regulatory review in Japan and other countries.

It is particularly worth mentioning that,Bavencio is the only one for first-line treatment of stage IIIClinical TrialImmunotherapy that significantly prolongs overall survival (OS) in patients with locally advanced or metastatic UC.

United StatesFDAfull approval and the positive review opinion from the EU CHMP, both based on the positive results of the Phase III JAVELIN Bladder 100 study, with relevant data published in The New England Journal of Medicine (NEJM) this September. The data showed that, among all randomized patients andTumorIn the two major subgroups of PD-L1-positive patients, first-line maintenance treatment with Bavencio plus best supportive care (BSC) significantly prolonged overall survival (OS) and significantly improved the one-year survival rate compared with BSC alone. The clinical benefits of Bavencio were demonstrated across a range of patient populations.

Pfizer Global Product DevelopmentTumorChris Boshoff, MD, Chief Development Officer, stated: “In Europe, patients with locally advanced or metastatic urothelial carcinoma have an urgent unmet need for additional treatment options that may extend survival. The overall survival results from the JAVELIN Bladder 100 study demonstrate that first-line maintenance therapy with Bavencio represents a significant advance for patients with locally advanced or metastatic urothelial carcinoma. If approved, it has the potential to change the treatment paradigm for patients in Europe.”

Bladder Cancer (Image source: medscape.com)

JAVELIN Bladder 100 (NCT02603432) 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 whose disease did not progress after induction chemotherapy (assessed according to RECIST v1.1) were randomly assigned to receive either Bavencio plus BSC or BSC alone. The primary endpoint was assessed in all randomized patients and PD-L1-positiveTumorOverall Survival (OS) in Patients. In this study, Best Supportive Care (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 met the primary endpoint of OS: in two co-primary populations (all randomized patients, PD-L1 positiveTumorpatients), Bavencio + BSC resulted in a statistically significant improvement in OS compared with BSC alone.

—Among all randomized patients (n=700), compared with the BSC group, the Bavencio + BSC group demonstrated a significantly prolonged median OS (21.4 months vs. 14.3 months), a 31% reduction in the risk of death (HR = 0.69; 95% CI: 0.56–0.86; p < 0.001), and substantially improved 12-month survival rates (71% vs. 58%) and 18-month survival rates (61% vs. 44%).

——In PD-L1-positiveTumorAmong patients (n=358), compared with BSC, Bavencio + BSC demonstrated a greater OS benefit, reducing the risk of death by 44% (HR=0.56; 95% CI: 0.40-0.79; p<0.001), and significantly improving the 12-month survival rate (79.1% vs 60.4%).

——Results of Exploratory Subgroup AnalysisResults: Bavencio plus best supportive care (BSC) as first-line maintenance therapy demonstrated consistent efficacy outcomes across all prespecified subgroups, including best response to first-line chemotherapy, type of chemotherapy regimen, baseline metastatic sites, and other baseline factors. Specifically: (1) By response to first-line chemotherapy, the hazard ratios (HRs) for overall survival (OS) were 0.69 for patients with complete or partial response and 0.70 for those with stable disease; (2) By first-line chemotherapy regimen, the HRs for OS were 0.69 for gemcitabine plus cisplatin and 0.66 for gemcitabine plus carboplatin.

In this study, the safety profile of Bavencio was consistent with that observed in the JAVELIN monotherapy clinical development program. According to this study, Bavencio is the firstClinical TrialsThe first-line immunotherapy for advanced urothelial carcinoma (UC) in China to demonstrate a statistically significant improvement in overall survival (OS). For the past 30 years, chemotherapy has been the standard of care as first-line treatment for patients with advanced urothelial carcinoma. Although this represents an effective short-term option for many patients, the majority will eventually experience disease progression, underscoring 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, and approximately 200,000 people worldwide died from the disease. Urothelial carcinoma (UC) accounts for about 90% of bladder cancers. For patients with advanced UC, the 5-year survival rate is only 5%. It is estimated that around 4% of bladder cancer patients are already at an advanced stage at the time of diagnosis.

Currently, platinum-based chemotherapy is the first-line standard of care for advanced urothelial carcinoma (UC). Despite high initial response rates, durable responses and complete remissions are uncommon following first-line chemotherapy, with most patients ultimately experiencing disease progression within nine months of initiating treatment. Given the poor prognosis associated with disease progression after first-line chemotherapy in patients with advanced UC, there is an urgent need for additional therapeutic options to extend survival.

Bavencio is a PD-(L)1 tumor immunotherapy, a class of cancer immunotherapies that has garnered significant attention. It aims to harness the body’s own immune system to fight cancer by blocking the PD-1/PD-L1 signaling pathway, thereby inducing cancer cell death, and holds potential for treating various types of tumors. Bavencio has been demonstrated 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 shown in preclinical models to release T cell-mediated anti-TumorInhibitory Effect on Immune Response.

In November 2014, Pfizer signed 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, etc. (Bioon.com)

Original Source: BAVENCIO® (AVELUMAB) RECEIVES POSITIVE CHMP OPINION FOR FIRST-LINE MAINTENANCE TREATMENT OF LOCALLY ADVANCED OR METASTATIC UROTHELIAL CARCINOMA