The U.S. Food and Drug Administration (FDA) has approved Bavencio (avelumab) as a first-line maintenance therapy for people with advanced urothelial carcinoma — a type of bladder cancer — whose disease did not worsen while receiving platinum-based chemotherapy.
The decision was based on data from the ongoing JAVELIN Bladder 100 Phase 3 trial (NCT02603432). That data showed that Bavencio plus best supportive care significantly prolonged overall survival and the time patients lived without disease worsening compared with standard-of-care supportive therapies alone.
“As the first immunotherapy to demonstrate a statistically significant improvement in overall survival in the first-line setting in locally advanced or metastatic urothelial carcinoma, the FDA approval of avelumab is one of the most significant advances in the treatment paradigm in this setting in 30 years,” Petros Grivas, MD, PhD, one of the principal investigators in the JAVELIN Bladder 100 trial, said in a press release.
Earlier this year, the FDA granted its breakthrough therapy designation to Bavencio based on data from JAVELIN Bladder 100. Earning that designation requires preliminary clinical evidence demonstrating that a treatment candidate may provide substantial improvement over available therapies.
The U.S. regulatory agency also had granted priority review to the supplemental biologics license application (sBLA) submitted by the therapy’s developers, Pfizer and EMD Serono (known as Merck KGaA outside the U.S.). Priority review speeds an application’s review from the standard 10-month period to six months.
Bavencio is an immune checkpoint inhibitor that works by preventing the PD-L1 protein on cancer cells from interacting with the PD-1 receptor found on the surface of immune cells. Malignant cells use that mechanism to evade the immune system.
JAVELIN Bladder 100 is investigating whether the use of Bavencio plus best supportive care as a first-line maintenance therapy would be more beneficial to patients with advanced urothelial carcinoma whose disease remained stable or responded to initial platinum-based chemo, compared with supportive care alone.
The study’s main goal was to assess the effects of treatment on overall survival. This was evaluated both in the overall population participating in the study, and in the subgroup of patients whose tumors contained PD-L1.
The secondary goals included the time patients lived without signs of disease progression, the percentage of patients responding to treatment, and safety.
Interim data from the study, presented at the American Society of Clinical Oncology (ASCO) 2020 Virtual Annual Meeting, held recently online, showed the addition of Bavencio to supportive care prolonged the time patients lived from a median of 14.3 to 21.4 months. The risk of death in the overall population was reduced by 31%.
The survival benefits were even greater in the subgroup of patients with PD-L1-positive tumors. The median overall survival was not reached for those receiving Bavencio — meaning that more than 50% of the participants were still alive at the time of the analysis. In comparison, those receiving supportive care alone had a median overall survival of 17.1 months. In this patient subgroup, Bavencio lowered the risk of death by 44%.
Bavencio also increased the time patients lived without signs of disease progression from 2.0 to 3.7 months.
The therapy was found to have a manageable safety profile that was consistent with previous studies. The incidence of adverse events was higher among those receiving Bavencio (47.4%) compared with those on supportive care alone (25.2%). The most common adverse events reported included urinary tract infections, anemia, blood in the urine, fatigue, and back pain.
“With median overall survival of more than 21 months measured from randomization, the longest overall survival in a Phase III trial in advanced urothelial carcinoma, the JAVELIN Bladder 100 regimen with avelumab as a first-line switch maintenance treatment has the potential to become a new standard of care based on its proven ability to reinforce the benefit (response or stable disease) of induction chemotherapy and extend the lives of patients,” Grivas said.
The FDA had previously approved Bavencio, under its accelerated approval program, as a second-line treatment for people with advanced urothelial carcinoma whose disease progressed while or shortly after receiving first-line platinum-based chemotherapy.
Full approval required confirmation of the medication’s clinical benefit in confirmatory trials, which has now been provided by JAVELIN Bladder 100. Based on these findings, the FDA has now converted Bavencio’s initial accelerated approval into a full approval for this indication.
“Today’s approval of Bavencio in the most common type of advanced bladder cancer underscores our commitment to advancing scientific innovation and transforming outcomes for people with genitourinary cancers,” said Andy Schmeltz, global president of Pfizer Oncology.
Rehan Verjee, president of EMD Serono, said the two companies’ focus now is to work with the genitourinary community to ensure that this “novel and potentially life-changing treatment paradigm” is integrated as rapidly as possible into clinical practice.
“With this approval for Bavencio, we have the opportunity to fundamentally shift the standard of care in the first-line setting of advanced bladder cancer,” Verjee said.
The companies have established a reimbursement support program called CoverOne to facilitate patient access to Bavencio. U.S. patients who received a prescription for the medication may be eligible to apply for reimbursement. More information about the program can be found here.
The companies’ sBLA was reviewed under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to improve the efficiency of the review process. Its goal is to make safe and effective medications available to patients as soon as possible.
