An FDA advisory panel is set to review whether the data on an investigational PD-1 immune checkpoint inhibitor in squamous carcinoma of the anal canal (SCAC) are sufficient for accelerated approval.
On Thursday, the Oncologic Drugs Advisory Committee (ODAC) will consider whether the results of the phase II POD1UM-202 trial alone support the early approval of retifanlimab in locally advanced or metastatic SCAC patients who have progressed on or are refractory to platinum-based chemotherapy, or whether a confirmatory randomized trial should be a prerequisite.
Carboplatin plus paclitaxel is currently the preferred first-line regimen for locally advanced or metastatic SCAC, and there are no approved second-line treatments in the metastatic setting. There is a clear unmet need for patients who progress on chemotherapy, according to the drug’s sponsor, Incyte.
POD1UM-202 is an ongoing, open-label, single-arm clinical trial to assess the safety and efficacy of retifanlimab, with objective response rate (ORR) as its primary endpoint. Based on a June 8, 2020 data cutoff, 94 patients were enrolled in the trial and received at least one dose of retifanlimab.
Responses were seen in 13 patients, for an ORR of 14% (95% CI 8%-22%). Median estimated duration of response was 9.5 months, while median progression-free survival (PFS) and overall survival were 2.3 and 10.1 months, respectively.
According to the FDA’s briefing document, the therapy’s toxicity profile was consistent with that of approved immune checkpoint inhibitors, with no new safety signals identified.
“However, given the relatively small size of the safety database with respect to the SCAC population and the single-arm nature of the trial, residual uncertainty remains regarding the risks in the indicated population,” FDA staff observed. They also noted that the trial did not include a sufficient number of patients 65 years or older, nor enough patients with HIV-positive status to draw conclusions about the drug’s safety profile in those subgroups.
“Given the uncertainties with respect to risk/benefit based on these results and the potential for serious toxicities in a subgroup of patients who receive retifanlimab, confirmation of a clinical benefit with a randomized controlled trial is needed,” FDA staff suggested.
The proposed confirmatory trial — POD1UM-303 — is an ongoing randomized, double-blind, placebo-controlled clinical trial investigating chemotherapy plus either retifanlimab or placebo. The primary endpoint is progression-free survival, and the trial is powered to demonstrate a 33% reduction in the PFS hazard ratio. Overall survival is a key secondary endpoint.
In its briefing document, FDA staff pointed out that in order to support accelerated approval based on intermediate endpoints, the magnitude of the effect on the endpoint “should be reasonably likely to predict clinical benefit.” However, they indicated that it is unclear whether the low ORR demonstrated in POD1UM-202 does so, “particularly given the inconsistent relationship between low response rate and outcomes in randomized trials of other anti-PD-1/PD-L1 antibodies.”
Thus the questions the committee will consider are whether the ORR observed in POD1UM-202 is reasonably likely to predict clinical benefit, and should a regulatory decision on retifanlimab for this indication be deferred until results are available from POD1UM-303.
Last Updated June 23, 2021
Source: MedicalNewsToday.com
