Written By: Pharmacally Medical News Desk
The Japan Ministry of Health, Labour and Welfare (MHLW) has approved Zynyz (Retifanlimab) in combination with carboplatin and paclitaxel for the first-line treatment of adults with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). This marks the first regulatory approval for Zynyz in Japan and establishes the therapy as the first and only approved first-line option for SCAC in the country.
Yasuyuki Ishida, General Manager of Incyte Biosciences Japan G.K., noted that this approval provides an important new option for patients and families facing this aggressive and often under-recognized cancer.
Basis of Approval: POD1UM-303/InterAACT2 Trial
The approval is supported by results from the Phase 3 POD1UM-303/InterAACT2 trial (NCT04472429), which evaluated Retifanlimab plus platinum-based chemotherapy in adults with metastatic or inoperable locally recurrent SCAC who had not received prior systemic chemotherapy.
Key outcomes published in The Lancet journal includes
37% reduction in risk of progression or death compared with placebo plus chemotherapy.
Median progression-free survival (PFS)
9.3 months with Zynyz plus chemotherapy,
7.4 months with placebo plus chemotherapy
No new safety signals identified
Serious adverse reactions were reported in 47% of patients receiving Zynyz with chemotherapy. The most frequent serious events occurring in 2% or more of patients included sepsis, pulmonary embolism, diarrhea, and vomiting.
Understanding SCAC
Squamous cell carcinoma of the anal canal is the most common form of anal cancer, accounting for about 85 percent of cases worldwide. Although rare, its incidence has been rising by roughly 3 percent each year. In Japan, SCAC represents about 16 to 24 percent of anal canal cancers, while adenocarcinoma remains the predominant type overall, and the total incidence of anal canal cancers is estimated at 0.26 to 0.41 per 100,000 people. Up to 90 percent of SCAC cases are linked to human papillomavirus infection, and people living with HIV have a much higher risk. Because symptoms such as itching, pain, bleeding, or changes in bowel habits can mimic benign conditions like haemorrhoids, many patients are diagnosed at more advanced stages.
Symptoms such as pain, itching, bleeding, or bowel habit changes often resemble benign conditions like haemorrhoids, which can delay diagnosis and result in many patients presenting with advanced disease.
How Zynyz Works
Retifanlimab is a humanized monoclonal antibody that targets the programmed death receptor-1 (PD-1) pathway. By blocking PD-1, it helps restore anti-tumor immune responses. When combined with chemotherapy, this dual approach appears to enhance disease control in SCAC patients.
Zynyz is marketed by Incyte in the United States, where it also holds an accelerated approval for metastatic or recurrent locally advanced Merkel cell carcinoma. Continued approval for that indication depends on confirmatory data.
For safety, healthcare professionals should refer to the Japanese package insert and guidance from the Pharmaceuticals and Medical Devices Agency for detailed information on dosing, contraindications, and monitoring recommendations.
In May 2025, the U.S. FDA approved Zynyz plus chemotherapy for first-line treatment of advanced SCAC. Incyte has also submitted a Type II variation Marketing Authorization Application to the European Medicines Agency for use in advanced SCAC in Europe.
The broader POD1UM program continues to evaluate Retifanlimab across multiple solid tumors, including non-small cell lung cancer.
The MHLW approval offers a new standard treatment pathway for patients with advanced SCAC in Japan, a setting historically limited to chemotherapy alone. With expanding global regulatory submissions and ongoing trials, Retifanlimab is positioned to play a growing role in immuno-oncology strategies for rare but challenging cancers.
References
Incyte Japan Announces Approval of Zynyz® (Retifanlimab) for the First-Line Treatment of Advanced Anal Cancer, 22 December 2025, https://investor.incyte.com/news-releases/news-release-details/incyte-japan-announces-approval-zynyzr-retifanlimab-first-line
Carboplatin-paclitaxel With Retifanlimab or Placebo in Participants with Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (POD1UM-303/InterAACT 2), ClinicalTrials.gov ID NCT04472429, https://clinicaltrials.gov/study/NCT04472429
Rao, Sheela et al, Retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic squamous cell carcinoma of the anal canal (POD1UM-303/InterAACT-2): a global, phase 3 randomised controlled trial, The Lancet, Volume 405, Issue 10495, 2144 – 2152, DOI: 10.1016/S0140-6736(25)00631-2