Retifanlimab-dlwr Approved for Advanced Squamous Cell Carcinoma of the Anal Canal
Expert Perspectives
By Lyn Brook
Published
The FDA has granted approval to retifanlimab-dlwr (Zynyz®, Incyte Corporation) in combination with carboplatin and paclitaxel for the first-line treatment of adults with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). Retifanlimab-dlwr has also been approved as a single-agent for adults with locally recurrent or metastatic SCAC whose disease has progressed on, or who are intolerant to, platinum-based chemotherapy.
Why This Approval Matters
“Inoperable locally recurrent/metastatic SCAC is associated with suboptimal progression-free survival (PFS) and overall survival (OS), despite high initial response rates to platinum-based chemo,” said Sheela Rao, MBBS, FCRCP, MD, a Consultant Medical Oncologist at The Royal Marsden Hospital, and colleagues, in their published results of the POD1UM-303/InterAACT 2 trial (NCT04472429), on which approval was based. “Retifanlimab, an anti–programmed cell death (PD)-1 monoclonal antibody, has shown antitumor activity in patients with advanced SCAC who progressed on platinum-based chemotherapy.”
Breaking Down the POD1UM-303/InterAACT 2: The Combination
The efficacy of retifanlimab-dlwr in combination with carboplatin and paclitaxel was evaluated in the POD1UM-303/InterAACT 2 trial, a phase 3, multicenter, double-blind study. The trial enrolled 308 patients with chemotherapy-naive, inoperable, locally recurrent or metastatic SCAC. Patients received carboplatin at a dose of area under the curve (AUC) 5, Day 1; and paclitaxel at a dose of 80 mg/m², Days 1, 8, and 15 for 6 cycles, and were randomized 1:1 to receive either retifanlimab-dlwr 500 mg intravenously every four weeks or placebo.
Key efficacy end points included PFS as assessed by blinded independent central review (BICR) according to RECIST v1.1, with OS as a key secondary end point. Additional end points included overall response rate (ORR) and duration of response (DOR). The results demonstrated a median PFS of 9.3 months in the retifanlimab-dlwr arm versus 7.4 months in the placebo arm. The interim analysis results of OS were not statistically significant, with a median OS of 29.2 months for retifanlimab-dlwr and 23 months for placebo. The ORR was 56% in the retifanlimab-dlwr arm and 44% in the placebo arm.
Breaking Down the POD1UM-202 Trial: The Single Agent
The efficacy of retifanlimab-dlwr as a single agent was evaluated in the POD1UM-202 trial (NCT03597295), an open-label, multicenter, single-arm study of 94 patients with locally recurrent or metastatic SCAC who had progressed on or were intolerant to platinum-based chemotherapy. Retifanlimab-dlwr was administered at 500 mg intravenously every four weeks until disease progression, unacceptable toxicity, or up to 24 months. The primary efficacy outcomes were ORR and DOR as assessed by independent review committee (IRC) per RECIST v1.1. Single-agent retifanlimab produced an ORR of 14% and a median DOR of 9.5 months.
Managing Adverse Events
The safety profile of retifanlimab-dlwr includes warnings for severe and fatal immune-mediated adverse events, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation (HSCT), and embryo-fetal toxicity. Clinicians should monitor for these events and manage according to established guidelines.
Dosing and Administration
The recommended dose of retifanlimab-dlwr is 500 mg every four weeks, in combination with carboplatin and paclitaxel for up to 12 months, or as monotherapy for up to 24 months, or until disease progression or unacceptable toxicity. Refer to the prescribing information for carboplatin and paclitaxel for dosing when used in combination.
Clinical Implications and Future Outlook
“This international study demonstrates encouraging efficacy and favorable benefit/risk ratio for retifanlimab plus standard-of-care chemotherapy as first-line treatment of locally recurrent/metastatic SCAC and suggests a new standard of care,” concluded Dr. Rao and colleagues.