Bavencio (avelumab), jointly manufactured and developed by EMD Serono and Pfizer, is approved to treat metastatic Merkel cell carcinoma (MCC), a type of aggressive skin cancer, and urothelial carcinoma, a type of cancer of the bladder or urinary tract.
The U.S. Food and Drug Administration (FDA) granted Bavencio accelerated approval for both indications — metastatic MCC (March 2017) and urothelial carcinoma (May 2017). Continued approval as a treatment for these diseases will depend on results in ongoing confirmatory trials.
How Bavencio works
Bavencio is a monoclonal antibody against programmed death ligand-1 (PD-L1), a cell-surface protein produced in excessive amounts by several cancers. In healthy cells, the PD-L1 protein binds to its receptor PD-1, found on the surface of immune system cells known as T-cells, to restrain or inhibit their growth and activity. This suppression serves as a check on T-cells, preventing the immune system from becoming overactive and mistaking healthy cells as foreign invaders and attacking them.
Cancer cells should be seen by the immune system as invaders. But tumors are known to use the immune-suppressing action of PD-L1 binding to PD-1 to evade immune attacks.
Monoclonal antibodies that block PD-L1, such as Bavencio, are designed to prevent or lessen immune suppression — to block the binding of the protein to its receptor — so that T-cells are more active and more likely to attack cancer cells.
Bavencio specifically binds to PD-L1 and inhibits the interaction between PD-L1 and PD-1, promoting an immune response against cancer cells.
Bavencio in clinical trials
Merkel cell carcinoma (MCC)
Bavencio’s approval to treat metastatic MCC in patients ages 12 and older was based on safety and efficacy data obtained from the ongoing JAVELIN Merkel 200 trial (NCT02155647). This open-label, single-arm and multicenter study was conducted in 88 patients with confirmed metastatic MCC. Bavencio was injected into the bloodstream, at a dose of 10 mg/kg, as a 60-minute infusion every two weeks. The primary measure of effectiveness was confirmed overall response rate (ORR), or the proportion of patients whose cancer shrank in response to treatment, with tumor response assessed every six weeks.
Interim results showed Bavencio to be well-tolerated and associated with long-lasting and clinically meaningful responses. ORR was 33 percent, with 11 percent complete and 22 percent partial response rates. Response duration ranged from 2.8 months to more than 23.3 months among the 29 patients who did respond, and 86 percent of responses lasted for six months or longer. The study is expected to complete by 2025.
The most common adverse reactions associated with the treatment were fatigue, muscle and bone pain, diarrhea, nausea, infusion-related reaction, rash, decreased appetite, and peripheral edema.
Bavencio was approved to treat patients with advanced urothelial carcinoma based on interim safety and efficacy data from the JAVELIN solid tumor trial (NCT01772004). This open-label, single-arm, and multicenter study, at the point of accelerated approval, had enrolled 242 patients (1,650 would take part in total) with locally advanced or metastatic urothelial carcinoma, whose disease progressed during or after platinum-containing chemotherapy, or within 12 months of adjuvant (helper drug) treatment with platinum-containing chemotherapy. Patients received Bavencio at a dose of 10 mg/kg injected into the bloodstream every two weeks.
In patients who were followed for at least 13 weeks, confirmed ORR was 13.3 percent. In patients followed for at least six months, confirmed ORR was 16.1 percent. Median time to response was two months. The median response duration had not been reached in patients followed for at least 13 weeks or six months at time of approval, but ranged from about 1.4 months to more than 17.4 months in both groups.
The most common adverse reactions observed were fatigue, infusion-related reaction, muscle and bone pain, nausea, decreased appetite, and urinary tract infection.
Non-small cell lung cancer (NSCLC)
The JAVELIN solid tumor trial (NCT01772004) also assessed Bavencio in a subgroup of patients with advanced NSCLC. Results showed that Bavencio was safe and demonstrated anti-cancer activity in these people.
These results led to an open-label Phase 3 study (NCT02576574) that aims to evaluate the safety and efficacy of Bavencio compared to platinum-based chemotherapy as a first-line treatment in patients with late-stage NSCLC. The study’s major efficacy measures are progression-free survival and overall survival. The study plans to enroll almost 2,000 patients globally, including at sites across U.S., and to finish in July 2024. Enrollment information is available by clicking on the trial’s identification number.
Bavencio is also being studied for the treatment of several other cancers, such as glioblastoma (NCT03047473), colorectal cancer (NCT03150706), nasopharyngeal cancer (NCT02875613), intestinal adenocarcinoma (NCT03000179), endometrial cancer (NCT02912572), osteosarcoma (NCT03006848), and ovarian cancer (NCT02718417).
The recommended dose of Bavencio is 10 mg/kg as a 60-minute intravenous infusion every two weeks. Patients need to be treated with an antihistamine and acetaminophen prior to the first four infusions of Bavencio.
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