May 18 2025

On May 15, 2025, the U.S. Food and Drug Administration (FDA) approved a new treatment called retifanlimab-dwlr (Zynyz®) for people with advanced anal cancer. This approval brings new option to patients facing this challenging disease.

Please note: The information in this post pertains to treatment approved by the U.S. FDA and is intended for U.S. patients. Retifanlimab-dwlr (Zynyz®) is not currently approved or available for patients in Europe or the United Kingdom.

What is Zynyz® / Retifanlimab-dwlr?

Retifanlimab-dwlr is an immunotherapy drug that helps your immune system recognize and fight cancer cells. It targets a specific protein called programmed-death receptor 1 (PD-1), which cancer cells use to hide from the immune system. By blocking PD-1, retifanlimab-dwlr helps your body’s immune defenses attack the cancer.

Retifanlimab-dwlr has been approved for two uses in anal cancer by the FDA:

  • With chemotherapy (carboplatin and paclitaxel) for adults with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) who have never had chemotherapy before.
  • As a single agent treatment for adults whose cancer has progressed or who cannot tolerate platinum-based chemotherapy.

What clinical studies led to FDA approval?

Retifanlimab-dwlr was tested in two key clinical trials:

POD1UM-303/InterAACT2 Trial (Phase 3)

  • Included 308 patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) who had not received chemotherapy before.
  • Patients were randomly assigned to receive chemotherapy plus retifanlimab or chemotherapy plus placebo.
  • Chemotherapy included carboplatin (a platinum-based drug) and paclitaxel, given on a schedule for 6 cycles.

POD1UM-202 Trial (Phase 2)

  • Included 94 patients with SCAC that had progressed after or who could not tolerate platinum chemotherapy.
  • Patients received retifanlimab alone every 4 weeks until disease progression or unacceptable side effects for up to 24 months.

What did the trials find?

In the POD1UM-303/InterAACT2 trial (retifanlimab plus chemotherapy vs chemotherapy alone):

  • Patients who received retifanlimab with chemotherapy lived longer without their cancer getting worse.
  • Median progression-free survival (PFS) was 9.3 months with retifanlimab compared to 7.4 months without it. This means the cancer was controlled for about 2 months longer on average.
  • Overall response rate (ORR), meaning how many patients’ tumors shrank, was higher with retifanlimab (56%) compared to chemotherapy alone (44%).
  • Interim results showed median overall survival (OS) was 29.2 months with retifanlimab vs 23 months without, although this difference was not statistically significant at the time.
  • Around 45% of patients initially receiving placebo later received retifanlimab after their disease progressed, which may have influenced overall survival results.

In the POD1UM-202 trial (retifanlimab alone):

  • 14% of patients saw their tumors shrink.
  • The median duration of response was 9.5 months, meaning that for those who responded, the benefit lasted for several months.

What are the treatment schedules and doses?

  • When given with chemotherapy (carboplatin and paclitaxel), retifanlimab-dwlr is given at 500 mg intravenously every 4 weeks for up to 12 months or until disease progression or unacceptable side effects.
  • As a single agent, retifanlimab-dwlr is given at 500 mg intravenously every 4 weeks for up to 24 months or until disease progression or unacceptable side effects.

What side effects should patients expect?

Like all treatments, retifanlimab-dwlr can cause side effects. Some of the most serious risks include:

  • Immune-related reactions: Since retifanlimab-dwlr activates the immune system, it can sometimes cause inflammation in organs like lungs, liver, intestines, or hormones, which can be serious or even fatal if untreated.
  • Infusion reactions: Reactions during the infusion of the drug may occur.
  • Other risks: Problems related to previous stem cell transplants and embryo-fetal toxicity (risk during pregnancy).

Your doctor will monitor you closely to manage any side effects.

What does the approval of retifanlimab-dwlr mean for patients with anal cancer?

Please note: This approval applies only to the United States. Retifanlimab-dwlr (Zynyz®) is not approved for use in Europe or the UK at this time.

  • This is the first new FDA-approved PD-1 inhibitor treatment for advanced anal cancer in the U.S. in decades.
  • It offers a new option for people with inoperable or metastatic anal cancer, improving disease control and potentially extending survival.
  • For patients who cannot tolerate chemotherapy, retifanlimab-dwlr as a single agent provides another option.
  • The approval reflects encouraging results from clinical trials and a commitment to advancing care for this rare cancer.

What should patients do next?

If you or a loved one has advanced anal cancer, discuss with your oncologist whether retifanlimab-dwlr may be a suitable treatment option. Your healthcare team can explain the benefits and risks and provide support throughout treatment.

In the USA, financial assistance and patient support programs are available to help with access to retifanlimab-dwlr. For more information, visit IncyteCARES.

Where can I learn more?

The full prescribing information for retifanlimab-dwlr will be available on the FDA website at Drugs@FDA.

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