Bavencio (avelumab) - 3 indications

Scroll down for information on each indication:

• Merkel cell carcinoma; approved 03/01/2017
• First-line treatment of advanced renal cell carcinoma in combination with Inlyta (axitinib); approved 05/01/2019
• Locally advanced or metastatic urothelial carcinoma; approved 06/01/2020

General Information

Bavencio (avelumab) is a programmed death ligand-1 (PD-L1) blocking antibody.

Bavencio is specifically indicated for the following:

• the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma.
• for use in combination with Inlyta (axitinib) for the first-line treatment of patients with advanced renal cell carcinoma (RCC).
• for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy.

Bavencio is supplied as a solution for intravenous infusion. Scroll down to see the recommended dosing schedules for each indication. 

Mechanism of Action

Bavencio (avelumab) is a programmed death ligand-1 (PD-L1) blocking antibody. PD-L1 may be expressed on tumor cells and tumor-infiltrating immune cells and can contribute to the inhibition of the anti-tumor immune response in the tumor microenvironment. Binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells and antigen presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation and cytokine production. Avelumab binds PD-L1 and blocks the interaction between PD-L1 and its receptors PD-1 and B7.1. This interaction releases the inhibitory effects of PD-L1 on the immune response resulting in the restoration of immune responses, including anti-tumor immune responses. 

Inlyta (axitinib) is a kinase inhibitor. It has been shown to inhibit receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression.

Side Effects

Adverse effects associated with the use of Bavencio may include, but are not limited to, the following:

• fatigue
• musculoskeletal pain
• diarrhea
• nausea
• infusion-related reaction
• rash
• decreased appetite
• peripheral edema

Adverse effects associated with the use of Bavencio plus Inlyta may include, but are not limited to, the following:

• diarrhea
• fatigue
• hypertension
• musculoskeletal pain
• nausea
• mucositis
• palmar-plantar erythrodysesthesia
• dysphonia
• decreased appetite
• hypothyroidism
• rash
• hepatotoxicity,
• cough,
• dyspnea
• abdominal pain
• headache

Indication 1 - Merkel cell carcinoma

approved 03/01/2017

Dosing/Administration

The recommended dose of Bavencio is 10 mg/kg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. 

Clinical Trial Results

The FDA approval of Bavencio for Merkel cell carcinoma was based on the JAVELIN Merkel 200 trial, an open-label, single-arm, multi-center study conducted in patients with histologically confirmed metastatic MCC whose disease had progressed on or after chemotherapy administered for distant metastatic disease. A total of 88 subjects received Bavencio 10 mg/kg as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. Patients with radiological disease progression not associated with significant clinical deterioration, defined as no new or worsening symptoms, no change in performance status for greater than 2 weeks, and no need for salvage therapy, could continue treatment. Tumor response assessments were performed every 6 weeks. The major efficacy outcome measures were confirmed overall response rate (ORR) according to RECIST v1.1 as assessed by a blinded independent central review committee (IRC) and IRC-assessed duration of response. The efficacy analysis was conducted when the last patient enrolled had completed 12 months of follow-up. The ORR was 33%, with a Complete response (CR) rate of 11.4% and a Partial response (PR) rate of 21.6%. 

Indication 2 - First-line treatment of advanced renal cell carcinoma in combination with Inlyta (axitinib)

approved 05/01/2019

Dosing/Administration

The recommended dose of Bavencio is 800 mg administered as an intravenous infusion over 60 minutes every 2 weeks in combination with Inlyta 5 mg orally taken twice daily (12 hours apart) with or without food until disease progression or unacceptable toxicity. When Inlyta is used in combination with Bavencio, dose escalation of Inlyta above the initial 5 mg dose may be considered at intervals of two weeks or longer. 

Clinical Trial Results

The FDA approval of Bavencio in combination with Inlyta was based on the Phase III JAVELIN Renal 101 study. The randomized (1:1), multicenter, open-label study of Bavencio in combination with Inlyta enrolled 886 patients with untreated advanced RCC regardless of tumor PD-L1 expression [intent-to-treat (ITT) population]. Patients with autoimmune disease or conditions requiring systemic immunosuppression were excluded. The major efficacy outcome measures were PFS as assessed by a Blinded Independent Central Review (BICR) using RECIST v1.1 and OS in patients with PD-L1-positive tumors using a clinical trial assay (PD-L1 expression level ≥1%). If PFS was statistically significant in patients with PD-L1-positive tumors, it was then tested in the ITT population. The combination significantly improved median progression-free survival (PFS) compared with sunitinib by more than five months in the intent-to-treat (ITT) patient population (median PFS for Bavencio in combination with Inlyta: 13.8 months versus sunitinib: 8.4 months). The ITT population included patients regardless of PD-L1 expression and across IMDC (International Metastatic Renal Cell Carcinoma Database) prognostic risk groups (favorable 21%, intermediate 62% and poor 16%). The objective response rate (ORR) was doubled in the ITT population with Bavencio in combination with Inlyta versus sunitinib (51.4% vs. 25.7%). With a median overall survival (OS) follow-up of 19 months, data for the trial's other primary endpoint of OS were immature, with 27% of deaths in the ITT population.

Indication 3 - locally advanced or metastatic urothelial carcinoma

approved 06/01/2020

Dosing/Administration

The recommended dose of Bavencio is 10 mg/kg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. 

Clinical Trial Results

The FDA approval of Bavencio for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy was based on the Phase III JAVELIN Bladder 100 study. The Phase III, multicenter, multinational, randomized, open-label, parallel-arm study investigated first-line maintenance treatment with Bavencio plus BSC versus BSC alone in patients with locally advanced or metastatic UC that did not progress with first-line platinum-containing chemotherapy as per RECIST v1.1. A total of 700 patients were randomly assigned to receive either Bavencio (10 mg/kg intravenous infusion every 2 weeks) plus BSC (n=350) or BSC alone (n=350). which demonstrated a significant 7.1-month improvement in median overall survival (OS) with Bavencio as first-line maintenance plus best supportive care (BSC) compared with BSC alone: 21.4 months vs. 14.3 months. This statistically significant improvement in OS represents a 31% reduction in the risk of death in the overall population. OS was measured from the time of randomization, after patients were treated with four to six cycles of gemcitabine plus cisplatin or carboplatin over a period of approximately four months.