The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of retifanlimab (Zynyz) for first-line use in combination with carboplatin and paclitaxel in adult patients with metastatic or inoperable locally recurrent squamous cell carcinoma of the anal canal (SCAC).1
The positive opinion is supported by data from the phase 3 P0D1UM-303/InterAACT2 trial (NCT04472429), in which the addition of retifanlimab to platinum-based chemotherapy (n = 154) led to a median progression-free survival (PFS) of 9.3 months (95% CI, 7.5-11.3) vs 7.4 months (95% CI, 7.1-7.7) with chemotherapy alone (n = 154; HR, 0.63; 95% CI, 0.47-0.84; P = .0006); this translated to a 37% reduction in the risk of disease progression or death.2 The median follow-up for the retifanlimab and placebo arms was 7.6 months (range, 0-33.9) and 7.1 months (range, 0-27.4), respectively.
Advancing First-Line Care in Advanced SCAC
- The CHMP has recommended retifanlimab combined with carboplatin and paclitaxel as a first-line option for advanced SCAC.
- In the phase 3 P0D1UM-303trial, the addition of retifanlimab improved progression-free survival and response rates compared with chemotherapy alone.
- These findings support immunotherapy plus chemotherapy as a potential new frontline standard in a setting with few effective treatments.
“Today’s positive CHMP opinion is an important step towards addressing the urgent need for new treatment options for patients in Europe with advanced SCAC, a disease which has seen limited innovation for decades,” Lee Heeson, executive vice president and head of Incyte International, stated in a news release.1 “If approved, [retifanlimab] in combination with platinum-based chemotherapy has the potential to become a new standard-of-care for patients living with this rare and difficult-to-treat cancer.”
How was the P0D1UM-303 study designed?
The multicenter, double-blind, controlled, phase 3 trial enrolled patients with inoperable locally recurrent or metastatic SCAC who were at least 18 years of age and had an ECOG performance status no higher than 1.2 Patients could not have previously received systemic therapy, but those with well controlled human immunodeficiency virus were permitted.
Participants were randomly assigned 1:1 to receive retifanlimab at 500 mg or placebo plus standard carboplatin and paclitaxel. All patients received up to 6 cycles of carboplatin at area under the curve 5 mg/mL on day 1 plus paclitaxel at 80 mg/m2 on days 1, 8, and 15. They were stratified by PD-L1 expression (< 1% vs ≥ 1%), disease status (locally recurrent vs metastatic), and region (Australia, the European Union (EU), North America, and the United Kingdom (UK) vs the rest of the world).
The primary end point of the study was PFS, and secondary end points included overall survival (OS), overall response rate (ORR), duration of response (DOR), disease control rate (DCR), pharmacokinetics, and safety.
Demographics and disease characteristics were balanced at baseline. The median patient age was 61.5 years (range, 29-86) and most were female (retifanlimab, 68%; placebo, 77%), White (86%; 89%), and from Australia, the EU, North America, or the UK (95%; 95%). Moreover, most patients had prior radiotherapy (68%; 73%) and metastatic disease (82%; 82%). Eighteen percent of patients in both arms had locally recurrent disease and 36% of those in both arms had metastatic disease in the liver. Additionally, 53% and 56% of those in the retifanlimab and placebo arms, respectively, had an ECOG performance status of 0.
What additional efficacy data were reported with retifanlimab in SCAC?
The median OS was 29.2 months (95% CI, 24.2-not evaluable) with retifanlimab plus chemotherapy vs 23.0 months (95% CI, 15.1-27.9) with chemotherapy alone.
Moreover, the retifanlimab combination elicited an ORR of 55.8% (95% CI, 47.6%-63.8%) vs 44.2% (95% CI, 36.2%-52.4%) with chemotherapy alone (P = .013). Among those in the retifanlimab arm who responded to treatment, 22% had a complete response, 34% had a partial response, and 29% had stable disease; in the chemotherapy-alone arm, these respective rates were 14%, 31%, and 34%. The median DOR in the retifanlimab arm was 14.0 months (95% CI, 8.6-22.2) vs 7.2 months (95% CI, 5.6-9.3) in the chemotherapy-alone arm. The DCR with retifanlimab plus chemotherapy was 87.0% (95% CI, 80.7%-91.9%) vs 79.9% (95% CI, 72.7%-85.9%) with chemotherapy lone.
What was the safety profile of retifanlimab plus platinum-based chemotherapy in SCAC?
The treatment duration with retifanlimab and chemotherapy was 7.4 months (range, 0.03-14.6) and 6.8 months (range, 0.03-14.6) with chemotherapy alone. All patients in both arms experienced adverse effects (AEs) with 83% and 75% of patients, respectively, experiencing grade 3 or higher AEs.
Additionally, 47% of those in the retifanlimab arm and 39% of those in the placebo arm experienced serious AEs; 3% and 1% died. Serious AEs related to treatment occurred in 16% of those who received retifanlimab and 7% of those who were given placebo. Immune-related AEs occurred in 49% and 26% of those in the respective arms. AEs led to discontinuation of retifanlimab or placebo in 11% and 3% of patients, respectively.
What is the significance of retifanlimab in advanced SCAC?
In May 2025, the FDA cleared retifanlimab-dlwr for use in combination with carboplatin and carboplatin in the frontline treatment of adult patients with inoperable locally recurrent or metastatic SCAC; the agency also approved the drug for use as a single agent in adult patients with recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy.3 The decision was based on findings from P0D1UM-303.
“This FDA approval [indicates] an immunotherapy drug for the first time, and [this is] an area where there is a significant unmet need,” Marwan Fakih, MD, said in an exclusive interview with OncLive®.4,5 Fakih is a professor in Department of Medical Oncology & Therapeutics Research, associate director for Clinical Sciences Medical, director of the Briskin Center for Clinical Research, division chief of GI Medical Oncology, and co-director of the Gastrointestinal Cancer Program at City of Hope.
Previously, in January 2021, the FDA granted priority review to a biologics license application for retifanlimab in adult patients with locally advanced or metastatic SCAC who were intolerant of or who had progressed on platinum-based chemotherapy based on data from the phase 2 POD1UM-202 trial (NCT03597295).6 In June 2021, the FDA’s Oncologic Drugs Advisory Committee voted 13 to 4 to hold off on a decision regarding the accelerated approval of the immunotherapy for use in this population.7 A month later, the agency issued a complete response letter to Incyte Corporation, the drug developer, citing the need for more data showcasing the clinical benefit of the immunotherapy in that population.8
The European Commission is currently reviewing the CHMP opinion.1
References
- Incyte announces positive CHMP opinion for Zynyz (retifanlimab) for first-line treatment of advanced squamous cell carcinoma of the anal canal (SCAC). News release. Incyte. January 30, 2026. Accessed February 5, 2026. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-positive-chmp-opinion-zynyzr-retifanlimab-first
- Rao S, Samalin-Scalzi E, Evesque L, 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. Lancet. 2025;405(10495):2144-2152. doi:10.1016/S0140-6736(25)00631-2
- Incyte announces FDA approval of Zynyz (retifanlimab-dlwr) making it the first and only approved first-line treatment for advanced anal cancer patients in the United States. News release. Incyte. May 15, 2025. Accessed February 5, 2026. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-fda-approval-zynyzr-retifanlimab-dlwr-making-it
- Fakih MG. Dr Fakih on the FDA approval of retifanlimab for advanced anal cancer. OncLive.com. May 20, 2025. Accessed February 5, 2026. https://www.onclive.com/view/dr-fakih-on-the-fda-approval-of-retifanlimab-for-advanced-anal-cancer
- Seymour C. Retifanlimab displaces chemo alone as the frontline standard of care in SCAC: Q&A with Marwan G. Fakih, MD. OncLive.com. September 17, 2025. Accessed February 5, 2026. https://www.onclive.com/view/retifanlimab-displaces-chemo-alone-as-the-frontline-standard-of-care-in-scac
- Incyte announces acceptance and priority review of BLA for retifanlimab as a potential treatment for patients with squamous cell carcinoma of the anal canal (SCAC). News release. Zai Lab. January 21, 2021. Accessed February 5, 2026. https://ir.zailaboratory.com/news-releases/news-release-details/incyte-announces-acceptance-and-priority-review-bla-retifanlimab
- Oncologic Drugs Advisory Committee (ODAC) Meeting. FDA. June 24, 2021. Accessed February 5, 2026. https://www.youtube.com/watch?v=zj1lRsDwWB0
- Incyte provides regulatory update on retifanlimab for the treatment of certain patients with squamous cell carcinoma of the anal canal (SCAC). News release. Incyte Corporation. July 23, 2021. Accessed February 5, 2026. https://www.businesswire.com/news/home/20210723005449/en/Incyte-Provides-Regulatory-Update-on-Retifanlimab-for-the-Treatment-of-Certain-Patients-with-Squamous-Cell-Carcinoma-of-the-Anal-Canal-SCAC
