EMA CHMP recommends first-line retifanlimab plus carboplatin/paclitaxel for advanced anal cancer, backed by phase 3 P0D1UM-303 data.
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
“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.”
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.
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.
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.
In May 2025, the FDA cleared
“This FDA approval [indicates] an immunotherapy drug for the first time, and [this is] an area where there is a significant unmet need,”
Previously, in January 2021, the
The European Commission is currently reviewing the CHMP opinion.1
