Retifanlimab, a PD-1 inhibitor, has demonstrated clinically meaningful and durable antitumor activity in patients with locally advanced or metastatic squamous carcinoma of the anal canal (SCAC) who have progressed on or are intolerant to platinum-based chemotherapy. The POD1UM-202 study, a phase II trial, evaluated retifanlimab in this patient population, showing promising results that warrant further investigation. These findings offer a potential new treatment option for patients with limited alternatives.
Study Design and Patient Population
The POD1UM-202 study was an open-label, single-arm, multicenter phase II trial. It enrolled 94 patients with locally advanced or metastatic SCAC who had progressed after platinum-based chemotherapy. Patients received 500 mg of retifanlimab intravenously every 4 weeks for up to 26 cycles. The primary endpoint was overall response rate (ORR) as assessed by independent central review (ICR). Secondary endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.
Clinically Meaningful Antitumor Activity
The study reported an ORR of 13.8% (95% CI: 7.6% to 22.5%), with 1 complete response (1.1%) and 12 partial responses (12.8%). Stable disease was observed in 33 patients (35.1%), resulting in a DCR of 48.9% (95% CI: 38.5% to 59.5%). Responses were observed regardless of HIV or HPV status, PD-L1 expression, or liver metastases. The median DOR was 9.5 months (range, 5.6 months-not estimable). Median PFS was 2.3 months (95% CI: 1.9-3.6), and median OS was 10.1 months (95% CI: 7.9-not estimable).
Safety and Tolerability
Retifanlimab's safety profile in this population was consistent with previous experience for the PD-(L)1 inhibitor class. Treatment-emergent adverse events (TEAEs) were common, with 95.7% of patients experiencing at least one TEAE and 58.5% experiencing grade ≥3 TEAEs. Treatment-related AEs occurred in 58.5% of patients; the most common were pruritus (11.7%), fatigue (9.6%), and diarrhea (8.5%). Immune-related adverse events (irAEs) were reported in 25.5% of patients, most of which were grade ≤2 in severity.
Impact on Clinical Practice
"Retifanlimab demonstrated clinically meaningful and durable antitumor activity and an acceptable safety profile in patients with locally advanced or metastatic SCAC who have progressed on or are intolerant to platinum-based chemotherapy," the researchers concluded. These results support further investigation of retifanlimab in SCAC, with a phase III trial (POD1UM-303/InterAACT 2, NCT04472429) already underway to evaluate retifanlimab in combination with carboplatin and paclitaxel as a first-line therapy.
