Retifanlimab Approved for First-Line Treatment of Advanced Anal Cancer
According to Incyte, the U.S. Food and Drug Administration (FDA) has approved retifanlimab in combination with carboplatin and paclitaxel in the first-line setting for patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). The FDA additionally approved retifanlimab as a monotherapy for the treatment of patients with locally recurrent or with metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy. This regulatory decision was based on data from the POD1UM-202 and POD1UM-303/InterAACT2.
The phase 2 POD1UM-202 trial enrolled 94 patients with previously treated advanced or metastatic SCAC who had progressed following or were ineligible for platinum-based therapy. Patients received 500 mg retifanlimab intravenously every 4 weeks. The primary end point of this trial was overall response rate by independent central review. In this study, treatment with retifanlimab monotherapy resulted in an objective response rate of 14% and a disease control rate of 49%.
The phase 3, double-blind, controlled POD1UM-303/InterAACT2 trial enrolled 308 previously untreated patients with inoperable, locally recurrent or metastatic SCAC. Patients were randomized on a 1-to-1 basis to receive either 6 cycles of carboplatin-paclitaxel plus either placebo or retifanlimab. The primary end point for this study was progression-free survival. In this study, patients who received retifanlimab plus chemotherapy had a clinically meaningful and statistically significant 37% reduction in the risk of progression or death compared to the placebo arm, with a median PFS of 9.30 months vs 7.39 months, respectively (hazard ratio, 0.63; P = .0006).
In the POD1UM-202 trial, there were serious adverse events in 40% of patients, with the most common serious adverse events being non-urinary tract infection, perineal pain, abdominal pain, anemia, hemorrhage, diarrhea, pyrexia, urinary tract infection, musculoskeletal pain, and dyspnea.
In the POD1UM-303/InterAACT2 trial, there were no new safety signals observed, with 47% of patients who received retifanlimab plus chemotherapy experiencing a serious adverse event. The most common serious adverse events were sepsis, pulmonary embolism, diarrhea, and vomiting.
Source:
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. BusinessWire. Accessed May 15, 2025. https://www.businesswire.com/news/home/20250508024371/en/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
Rao S, Anandappa G, Capdevila J, et al. A phase II study of retifanlimab (INCMGA00012) in patients with squamous carcinoma of the anal canal who have progressed following platinum-based chemotherapy (POD1UM-202). ESMO Open. Published online: Aug 2022. doi:10.1016/j.esmoop.2022.100529.
Rao S, Samalin-Scalzi E, Evesque L, et al. LBA2 POD1UM-303/InterAACT 2: Phase III study of retifanlimab with carboplatin-paclitaxel (c-p) in patients (Pts) with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) not previously treated with systemic chemotherapy (chemo). Annals Oncol. Published online September 2024. doi: 10.1016/j.annonc.2024.08.2262
