FDA Approves Immunotherapy Bavencio for Metastatic Merkel Cell Carcinoma

The human anti-PD-L1 antibody is the first therapy for this rare skin cancer

The FDA has approved avelumab injection (intravenous) 20 mg/mL (Bavencio, EMD Serono) for the treatment of adults and pediatric patients 12 years of age and older with metastatic Merkel cell carcinoma (mMCC). The human anti-programmed death ligand-1 (PD-L1) antibody becomes the first FDA-approved therapy for patients with this rare and aggressive skin cancer.

This indication received accelerated approval based on tumor response and duration of response. Continued approval for the indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Avelumab was developed, reviewed, and approved through the FDA’s Breakthrough Therapy Designation and Priority Review programs.

The international clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs, including nine phase 3 trials in more than 4,000 patients across more than 15 tumor types. The efficacy and safety of avelumab were demonstrated in the JAVELIN Merkel 200 trial, an open-label, single-arm, multicenter study conducted in 88 patients with histologically confirmed mMCC whose disease had progressed on or after chemotherapy administered for distant metastatic disease.

Sixty-five percent of patients were reported to have had one prior anticancer therapy for mMCC, and 35% had two or more prior therapies. The major efficacy outcome measures were confirmed overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by a blinded independent central review committee (IRC) and IRC-assessed duration of response.

The ORR was 33% (95% confidence interval [CI], 23.3–43.8%). Eleven percent of patients experienced a complete response (95% CI, 6.6–19.9%), and 22% of patients experienced a partial response (95% CI, 13.5–31.7%). Tumor responses were durable, with 86% of responses lasting for at least six months (n = 25). Forty-five percent of responses lasted at least 12 months (n = 13). Duration of response ranged from 2.8 months to more than 23.3 months.

Historically, fewer than half of mMCC patients survive more than one year and fewer than 20% survive beyond five years.

The warnings and precautions for avelumab include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis, and renal dysfunction), infusion-related reactions, and embryo-fetal toxicity. The most common adverse reactions (reported in at least 20% of patients) included fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea (22%), infusion-related reactions (22%), rash (22%), decreased appetite (20%), and peripheral edema (20%).

Avelumab is designed to potentially engage both the adaptive and innate immune systems. By binding to PD-L1, this immunotherapy is thought to prevent tumor cells from using PD-L1 for protection against white blood cells, such as T cells, exposing them to antitumor responses. Avelumab has been shown to induce antibody-dependent cell-mediated cytotoxicity in vitro.

Source: EMD Serono; March 23, 2017.