Advisory panel recommends FDA defer decision on retifanlimab for anal cancer
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FDA’s Oncologic Drugs Advisory Committee today voted 13 to 4 to recommend deferral of a regulatory decision on retifanlimab for the treatment of certain patients with squamous cell carcinoma of the anal canal.
The panel did not support accelerated approval of retifanlimab (Incyte) — a PD-1 inhibitor administered via IV — for patients with locally advanced or metastatic disease who progressed on or were intolerant of platinum-based chemotherapy due in part to concerns about the low objective response rate in the open-label, phase 2 PODIUM-202 trial.
Squamous cell carcinoma of the anal canal — associated with HIV and HPV infections — accounts for approximately 3% of digestive system cancers. Patients with metastatic disease have poor 5-year survival outcomes and no FDA-approved therapies exist for those who have progressed after first-line therapy.
In making its decision, the ODAC panel considered efficacy and safety data from PODIUM-202, which included 94 patients (mean age, 62.1 years; 64.9% women) with previously treated locally advanced or metastatic squamous cell carcinoma of the anal canal. All patients progressed on or were intolerant of platinum-based chemotherapy, and nine (9.6%) had known HIV infection at baseline.
Patients received retifanlimab dosed at 500 mg via IV every 4 weeks. ORR assessed by independent central review served as the primary endpoint.
Results showed an ORR of 14%, with a 9.5-month (95% CI, 4.4-not estimable) median duration of response. Of note, responses occurred regardless HIV status, age, PD-L1 status or presence of liver metastases. Common adverse events included fatigue (any grade, 38%; grade 3-4, 6%) and diarrhea (any grade, 20%; grade 3-4, 3.2%).
Retifanlimab exhibited a safety profile consistent with that of approved immune checkpoint inhibitors, although an FDA briefing document stated that because of the small size of the safety database and the trial’s single-arm design, “residual uncertainty remains regarding the risks in the indicated patient population.”
Also uncertain is whether the current results of PODIUM-202 are reasonably likely to predict benefit, according to the FDA, which noted that the 13 patients who responded to retifanlimab had a small number of target lesions, and only seven had responses that lasted 6 months or longer.
Uncertainty requires a post-marketing requirement to verify clinical benefit, but only 10% of the planned trial population has enrolled on the ongoing randomized, placebo-controlled PODIUM-303 trial, the FDA background materials stated.
ODAC panelists also expressed concern that there appears to be an inconsistent relationship between low ORRs observed in other single-arm trials with anti-PD-1 or anti-PD-L1 antibodies and clinical benefit.
“I believe strongly in trying to find better treatments for rare diseases. However, I am also concerned about the low total number of respondents and low response rate,” Pamela Kunz, MD, associate professor of medicine/oncology at Yale School of Medicine and Yale Cancer Center, said after the vote. “I also have concerns about lack of applicability to a broader population given the lack of diversity of this particular patient group. It is important to include patients with HIV, but the number of these patients [included in the study] was low, in addition to a low number of underrepresented minorities.”
ODAC’s recommendation does not guarantee the FDA will defer a decision on retifanlimab in this patient setting. The FDA often follows the guidance of the advisory committee when deciding on drug applications, but the agency is not required to do so.
Data from PODIUM-303 are expected after study completion at the end of 2024.