The U.S. Food and Drug Administration (FDA) has approved Zynyz (retifanlimab-dlwr) for adults with advanced squamous cell carcinoma of the anal canal (SCAC). This approval introduces two new treatment options:
- First-Line Therapy: Zynyz is now approved to be used together with the chemotherapy drugs carboplatin and paclitaxel as the first treatment for adults whose anal cancer is inoperable (cannot be removed by surgery), has come back, or has spread to other parts of the body (metastatic).
- For Previously Treated Patients: Zynyz can also be used alone (monotherapy) for adults whose locally recurrent or metastatic SCAC has worsened after, or who cannot tolerate, platinum-based chemotherapy.
How Zynyz Works
Zynyz is a type of immunotherapy called a PD-1 inhibitor. It helps the immune system recognize and attack cancer cells.
What the Clinical Trials Showed
- In the phase 3 POD1UM-303/InterAACT2 trial, patients who received Zynyz with chemotherapy had a median progression-free survival (PFS) of 9.3 months, compared to 7.4 months for those who received chemotherapy alone. This means patients lived longer without their cancer getting worse.
- The combination also improved overall survival, with a median of 29.2 months versus 23 months for chemotherapy alone.
- The overall response rate (ORR) for the combination was 56%, with 22% of patients having their cancer disappear completely and 34% seeing their tumors shrink4.
- In the phase 2 POD1UM-202 trial, Zynyz used alone in patients who had already received chemotherapy resulted in a 14% response rate, with nearly half of patients (49%) experiencing disease control (tumors stopped growing or shrank).
Side Effects
- The most common serious side effects when Zynyz was used with chemotherapy included infections (such as sepsis), blood clots in the lungs, diarrhea, and vomiting.
- When used alone, serious side effects included infections, pain, anemia, bleeding, diarrhea, fever, urinary tract infections, muscle pain, and shortness of breath.
- No new safety concerns were identified in these studies.
This is the first time a PD-1 inhibitor has been approved for advanced anal cancer in the U.S., offering new hope for patients with limited treatment options. The approval provides both a new first-line therapy and an option for those whose cancer has returned or progressed after chemotherapy.
What Should Patients Do Next?
If you or a loved one has advanced SCAC, talk to your oncology team about whether Zynyz, either alone or in combination with chemotherapy, might be an option as part of your treatment plan.
References:
Zynyz. Prescribing information. Incyte. May 2025. Accessed May 15, 2025. https://www.zynyz.com/zynyz-prescribing-information
Rao S, Samalin-Scalzi E, Evesque L, et al. LBA2 POD1UM-303/InterAACT 2: Phase III study of retifanlimab with carboplatin-paclitaxel (c-p) in patients (Pts) with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) not previously treated with systemic chemotherapy (Chemo). Ann Onc. 2024;35:S1217. doi:10.1016/j.annonc.2024.08.2262
McNulty R. POD1UM-303/InterAACT 2: potentially practice-changing findings in SCAC. AJMC. September 14, 2024.
Rao S, Anandappa G, Capdevila J, et al. A phase II study of retifanlimab (INCMGA00012) in patients with squamous carcinoma of the anal canal who have progressed following platinum-based chemotherapy (POD1UM-202). ESMO Open. 2022;7(4):100529.
