Japan Approves Zynyz for First-Line Treatment of Advanced Anal Cancer
核心洞察
Japan's Ministry of Health, Labour and Welfare approved Zynyz (retifanlimab) in combination with carboplatin and paclitaxel as the first and only first-line treatment for advanced squamous cell carcinoma of the anal canal (搜索).
The approval was based on Phase 3 POD1UM-303/InterAACT2 trial data showing a statistically significant 37% reduction in risk of progression or death compared to placebo combination.
Patients receiving Zynyz combination therapy achieved a median progression-free survival of 9.3 months versus 7.4 months for placebo combination group.
Incyte Biosciences Japan G.K. (搜索) announced that Japan's Ministry of Health, Labour and Welfare (MHLW) has approved Zynyz (retifanlimab) in combination with carboplatin and paclitaxel for the first-line treatment of advanced squamous cell carcinoma of the anal canal (搜索) (SCAC). This approval establishes Zynyz as the first and only first-line treatment option for this rare cancer in Japan.
"Today's approval marks a significant milestone for patients with advanced anal cancer (搜索) in Japan – the MHLW's approval of Zynyz as the first and only first-line treatment for SCAC," said Yasuyuki Ishida, General Manager, Incyte Biosciences Japan G.K. (搜索) "By offering combination therapy with chemotherapy, Zynyz provides a vital new path forward for patients facing this challenging disease, addressing a significant unmet need in cancer care for patients with SCAC and their families."
Clinical Trial Results Drive Approval
The regulatory approval was based on data from the Phase 3 POD1UM-303/InterAACT2 trial (NCT04472429), which evaluated Zynyz in combination with platinum-based chemotherapy in adult patients with metastatic or inoperable locally recurrent SCAC who had not previously received systemic chemotherapy.
Results published in The Lancet demonstrated a statistically significant 37% reduction in the risk of progression or death (P=0.0006). Patients receiving the Zynyz and chemotherapy combination achieved a median progression-free survival (PFS) of 9.3 months compared to 7.4 months for patients in the placebo combination group.
Safety Profile
The trial identified no new safety concerns with the combination therapy. Serious adverse reactions occurred in 47% of patients receiving Zynyz in combination with chemotherapy. The most frequent serious adverse reactions (≥ 2% of patients) were sepsis, pulmonary embolism, diarrhea and vomiting.
Disease Burden in Japan
SCAC accounts for approximately 16% to 24% of anal canal cancer cases in Japan, with adenocarcinomas comprising about 70%. The overall incidence rate for anal canal cancer in Japan is approximately 0.26 to 0.41 per 100,000 persons.
Globally, SCAC represents the most common type of anal cancer (搜索), making up 85% of cases. It is a rare disease with an incidence that increases approximately 3% per year. About 90% of cases are associated with human papillomavirus (HPV) infection, which is the primary risk factor for anal cancer. HIV serves as an important amplifier of anal cancer risk, as people with HIV are 25 to 35 times more likely to develop the disease.
Global Regulatory Progress
This approval represents the first regulatory approval for Zynyz in Japan and the second global approval for this indication. In May 2025, the U.S. Food and Drug Administration (FDA) approved Zynyz in combination with carboplatin and paclitaxel for the first-line treatment of adult patients with inoperable locally recurrent or metastatic SCAC.
Incyte has also submitted a Type II variation Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for retifanlimab in advanced SCAC.
About Zynyz
Zynyz (retifanlimab) is a humanized monoclonal antibody targeting programmed death receptor-1 (搜索) (PD-1 (搜索)). The drug is indicated in combination with carboplatin and paclitaxel for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (搜索).
In the United States, Zynyz is also indicated for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (搜索) (MCC) under accelerated approval based on tumor response rate and duration of response.
The POD1UM (PD1 Clinical Program in Multiple Malignancies) clinical trial program for retifanlimab includes POD1UM-303, POD1UM-202 and several other Phase 1, 2 and 3 studies for patients with solid tumors, including a registration-directed trial evaluating retifanlimab in combination with platinum-based chemotherapy for patients with non-small cell lung cancer.