The BLA submission is based on data observed in the phase 2 POD1UM-202 trial of retifanlimab in previously treated patients with locally advanced or metastatic squamous cell carcinoma of the anal canal who had progressed on, or were intolerant of, standard platinum-based chemotherapy.
The FDA has accepted and granted priority review to the biologics license application (BLA) for the intravenous PD-1 inhibitor retifanlimab as a possible treatment for adult patients with locally advanced or metastatic squamous cell carcinoma of the anal canal (SCAC) who have progressed on, or who are refractory to, platinum-based chemotherapy, according to the drugs developer, Incyte.1
A prescription drug user fee act (PDUFA) target action was set by the FDA for July 25, 2021.
“Patients with SCAC who have progressed after first-line chemotherapy treatment currently have no approved treatments available, and we are encouraged that the FDA’s acceptance of this BLA for priority review brings us one step closer to addressing this historically neglected, yet important, tumor,” Lance Leopold, MD, group vice president of Immuno-Oncology Clinical Development at Incyte, said in a press release. “Despite SCAC being a rare disease, its incidence is increasing, and its impact is profound. We look forward to working with the FDA to potentially fill an unmet need and advance progress in SCAC for patients.”
The BLA submission is based on data observed in the open-label, single-arm, multicenter, phase 2 POD1UM-202 (NCT03597295) trial, which evaluated retifanlimab in the indicated patient population. Results from this trial were presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.2
Patients enrolled in the trial were given retifanlimab intravenously at a dose of 500 mg every 4 weeks. The trial enrolled a total of 94 patients, including several with well-controlled HIV infection.
The primary end point of the study is objective response rate (ORR) as determined by independent central review using RECIST v1.1. Key secondary end points include duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS), safety, and pharmacokinetics.
The study results presented at ESMO 2020 showed an ORR of 13.8% with retifanlimab monotherapy, including 1 complete response and 12 partial responses; 33 patients (35.1%) had stable disease. Responses were observed regardless of PD-L1 status, presence of liver metastases, age, or HIV-positive status and were also durable, with a median DOR of 9.5 months (5.6-not estimable).
Median PFS and OS were 2.3 (95% CI, 1.9-3.6) and 10.1 (95% CI, 7.9-NE) months, respectively. Importantly, responses were correlated with longer PFS and OS.
Treatment-related adverse events (AEs) of grade 3 or higher were reported in 11.7% of patients. Moreover, immune-related AEs of grade 3 or higher occurred in 6.4% of patients and treatment discontinuation due to immune-related AEs occurred in 2.1% of patients. The most common AEs observed (incidence ≥20%) were fatigue and diarrhea.
Retifanlimab was previously granted orphan drug designation by the FDA for the treatment of anal cancer. The investigational intravenous anti-PD1 agent is currently under evaluation in registration-directed trials as a monotherapy for patients with microsatellite instability–-high endometrial cancer, Merkel cell carcinoma, and SCAC as well as part of a combination regimen with platinum-based chemotherapy for patients with non–-small cell lung cancer and SCAC.
The phase 3 POD1UM-303/InterAACT 2 (NCT04472429) trial of retifanlimab in combination with carboplatin and paclitaxel in patients with inoperable locally recurrent or metastatic SCAC is now open and actively recruiting patients.
1. 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. Incyte. Published January 21, 2021. Accessed January 22, 2021. https://investor.incyte.com/press-releases/press-releases/2021/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/default.aspx
2. Rao S, Capdevila J, Gilbert D, et al. POD1UM-202: Phase II study of retifanlimab in patients (pts) with squamous carcinoma of the anal canal (SCAC) who progressed following platinum-based chemotherapy. Annals of Oncology. 2020;31(suppl 4):S1142-S1215. doi: 10.1016/annonc/annonc325