According to MacroGenics, retifanlimab is:

an investigational, humanized, proprietary anti-PD-1 monoclonal antibody being developed for use as monotherapy as well as in combination with other potential cancer therapeutics.

The therapy was then licensed to Incyte in 2017. Now, earlier this year, Incyte submitted a Biologics License Application (BLA) for retifanlimab. Altogether, the BLA was supported by data from the Phase 2 POD1UM-202 clinical trial. 94 patients enrolled in the trial. During the trial, patients received 500mg retifanlimab every 4 weeks (1 month) for up to 2 years. A majority of patients were white, female, and older in age (60+). 10% of patients were HIV-positive; 42% had liver metastases, and a whopping 97% of patients had already received platinum-based chemotherapy. Results from the study show:

•  1 patient had a complete response, while 12 had partial responses. Thus, the overall response rate was 13.8%. Patients saw a median response duration of 9.5 months.
• In some patients, retifanlimab controlled and suppressed tumors for over 1 year.
• Patients with HIV saw a 22.2% response rate, nearly 10% higher than those without HIV.
• Altogether, response rate did not seem to depend on elements like racial background, gender, or liver metastases.

Decision Deferral

However, ODAC members were concerned about specific elements of the trial. For example, some committee members, such as Dr. Pamela L. Kunz, believed that the study showed both a low response rate and a low number of respondents. Other committee members failed to see how the results would be translated into a broader and more diverse population. Within this study, there were only 4 Latinx patients, 1 Black patient, and 0 Asian patients. While HIV increases the risk of anal cancer by up to 30x, there were only 9 patients with HIV (9.6%) in the study.

Overall, the deferral decision was complex – and not without controversy. Since cases of squamous cell carcinoma of the anal canal have been rising over the past few years, and there are currently no approved therapies for patients with treatment-averse cancer, retifanlimab could fill an unmet need in this patient population. Dr. Phillip C. Hoffman, MD, an ODAC committee chair, voted to approve the drug so that patients would not need to wait potentially years.

However, the decision to defer accelerated approval until additional information is provided won out. Ultimately, with such a low response rate, the ODAC members wanted to ensure that approved treatments would meaningfully benefit patients with anal cancer. To do so, Incyte is currently recruiting patients for the Phase 3 POD1UM-303/InterAACT 2 study. However, results will not be available until 2025.

Anal Cancer

Anal cancer is a rare cancer which forms in the anal canal. Typically, the cancer begins in the cells right around the anal opening, though it may spread in later stages. While there is a small chance of anal cancer spreading, when it does, it usually spreads to the liver or lungs. Risk factors for developing anal cancer include human papillomavirus (HPV) infection, HIV, age (60+), engaging in anal sex, cigarette smoking, using immunosuppressants, having multiple sexual partners, or having a history of cervical, vulvar, or vaginal cancer. In a majority of anal cancers, HPV infection is present. Symptoms include:

• Anal or rectal pain, itching, or bleeding
• A mass or growth in the anal canal
• Anal discharge
• Changing bowel habits
• Narrow stools
• Swollen lymph nodes

Learn more about anal cancer.