FDA Approves First Advanced Anal Cancer Drug as First-Line Treatment

Incyte announced that the FDA has approved Zynyz (retifanlimab-dlwr) as a combination therapy for the treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) alongside carboplatin and paclitaxel (platinum-based chemotherapy). Zynyz was also approved as a monotherapy for adult patients with locally recurrent or metastatic SCAC or an intolerance to platinum-based chemotherapy, according to a news release published yesterday.

Squamous cell carcinoma of the anal canal is the most common type of anal cancer, making up 85% of cases today. Although anal cancer only accounts for less than 1% of all cancers, incidence is increasing approximately 3% every year. Most (90%) of cases are associated with human papillomavirus (HPV) infection.

Zynyz is a humanized monoclonal antibody that targets the programmed death receptor-1 (PD-1), mimicking the immune system’s ability to fight pathogens, like HPV.

Risk factors for anal cancer include having a compromised immune system from HIV or autoimmune disease.

Anal cancer symptoms can include anal or rectal discharge, a lump near the anus or pain and itching near the anus.

The recommended dosage of Zynyz for both indications is a 500mg intravenous infusion given over 30 minutes every four weeks until disease progression, according to the prescribing information. Zynyz as combination therapy can be given for up to 12 months and Zynyz as monotherapy can be given for up to 24 months.

Combination therapy approval was based on the results of the POD1UM-303/InterAACT2 study and of 308 patients given either Zynyz or placebo and chemotherapy. Patients treated with Zynyz showed a 37% reduction in the risk of progression or death compared with placebo.

Patients treated with both Zynyz and chemotherapy had an average of 9 months of progression-free survival, compared with placebo, which resulted in an average of 7 months of progression-free survival.

Adverse reactions occurred in 47% of patients, including sepsis (3%), pulmonary embolism (3%) and diarrhea (2%).

The monotherapy approval indication is based on the results of the POD1UM-202 study. Patients treated with Zynyz had an objective response rate of 14% and a disease control rate of 49%.

Adverse reactions occurred in 40% of patients, the most common being urinary tract infections, perineal pain and abdominal pain, all occurring in at least 2% of patients.

"Patients with inoperable locally recurrent or metastatic anal cancer have historically faced poor five-year survival rates and limited treatment options,” Marwan Fakih, M.D., professor of medical oncology & therapeutics research, associate director of clinical sciences and medical director, Briskin Center for Clinical Research, division chief, GI medical oncology, and co-director, gastrointestinal cancer program, City of Hope, said in the news release.  “The POD1UM data highlight the potential of Zynyz to be a meaningful new option and notably demonstrate that the addition of Zynyz to platinum-based chemotherapy significantly improves progression-free survival."

Eligible patients can visit IncyteCARES for financial support and ongoing education. Patients may pay as little as $15 out of pocket for their prescription if they are a commercially insured resident of the United States or Puerto Rico.

Zynyz is also FDA approved to treat adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma.