POD1UM-303/INTERAACT2 subgroup analyses and impact of delayed retifanlimab treatment on outcomes in patients with squamous cell carcinoma of the anal canal (SCAC).

3525 Background: SCAC is a rare cancer with high unmet medical need and no FDA-approved treatment options. POD1UM-303 is the only phase 3 study of systemic therapy completed to date in advanced SCAC. The study met its primary endpoint of progression-free survival (PFS; 9.3 mo in the retifanlimab group vs 7.4 mo in the placebo group [HR, 0.63; 95% CI, 0.47, 0.84; P = 0.0006]) (Rao S, et al. Ann Oncol . 2024;35:S1217). Based on these results, retifanlimab combined with carboplatin-paclitaxel represents a new standard of care (SOC) for inoperable locally recurrent/metastatic SCAC. Here, we present outcomes for predefined subgroups of interest in POD1UM-303 and exploratory analyses in patients who received open-label retifanlimab in the crossover phase of the study. Methods: The POD1UM-303 study design and methods were previously presented at ESMO 2024. PFS comparisons for predefined subgroups, including PD-L1 expression, region of enrollment, presence of liver metastases, extent of disease, as well as HPV and HIV status, were performed. Exploratory analyses of investigator-assessed response to retifanlimab, overall survival (OS), and safety during crossover treatment were also performed. Results: A total of 308 patients were enrolled (1:1) to receive retifanlimab or placebo with chemotherapy; 69 (45%) from the placebo + chemotherapy group received crossover treatment with retifanlimab monotherapy upon confirmed progression. A consistent PFS benefit in favor of retifanlimab + chemotherapy was observed for all predefined subgroups, including tumors with PD-L1 expression < 1%, patients with liver metastases, and regardless of HPV or HIV status. Median PFS in the retifanlimab + chemotherapy group was higher in the PD-L1 ≥1% vs PD-L1 < 1% groups (9.3 mo; HR, 0.64 vs 7.5 mo; HR, 0.53) but was not impacted by presence of liver metastases. During crossover, investigator-assessed overall response rate was qualitatively similar to that seen in the POD1UM-202 study, which enrolled a similar platinum-refractory population. Median OS for patients receiving crossover treatment with retifanlimab was 24.3 mo, compared with 29.2 mo for patients who were assigned to retifanlimab + chemotherapy at randomization. Safety during crossover was consistent with earlier observations and comparable with experience in POD1UM-202. Conclusions: The benefits of retifanlimab combined with carboplatin-paclitaxel extend to the broad population of SCAC, including those with tumors not expressing PD-L1 and liver metastases. Response rate and safety profile of retifanlimab monotherapy in the crossover period were consistent with the previous POD1UM-202 experience; however, exploratory analysis of survival in crossover patients suggests first-line retifanlimab with SOC chemotherapy is preferable to sequential treatment after progression on chemotherapy. Clinical trial information: NCT04472429 .