{"entity":{"id":"pod1um-303","kind":"trial","name":"POD1UM-303/InterAACT-2","aka":["POD1UM-303","InterAACT-2","INCMGA 0012-303"],"tldr":"POD1UM-303 showed that adding the immunotherapy retifanlimab to the standard carboplatin-paclitaxel chemotherapy for advanced anal cancer delayed progression by about two months in median terms and reduced the risk of progression by 37 percent, making it the first immunotherapy to improve first-line treatment of this cancer.","summary":"POD1UM-303/InterAACT-2 was a global double-blind phase 3 trial by Incyte that randomised 308 patients with untreated inoperable locally recurrent or metastatic anal squamous cell carcinoma to carboplatin and paclitaxel with retifanlimab 500 mg every four weeks or placebo. The primary endpoint was progression-free survival by blinded independent review.\n\nMedian progression-free survival was 9.3 months with retifanlimab against 7.4 months with placebo (hazard ratio 0.63), and interim overall survival also favoured the antibody; grade 3 or worse adverse events were 83.1 against 75.0 percent, with neutropenia and anaemia most common. Retifanlimab with carboplatin-paclitaxel was approved in the United States in May 2025 for this indication, and the corpus's metastatic anal cancer page lists it as the first-line standard with carboplatin-paclitaxel alone (InterAACT) where the antibody is unavailable.","status":"positive","asOf":"2026-09-22","links":[{"label":"ClinicalTrials.gov NCT04472429","url":"https://clinicaltrials.gov/study/NCT04472429"}],"tags":["soc-trials"],"related":[],"cancers":["metastatic-anal-cancer","anal"],"sections":[],"technologies":["checkpoint-inhibitor","cytotoxic-chemotherapy"],"targets":[],"drugs":["retifanlimab","carboplatin","paclitaxel"],"companies":["incyte"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-pod1um-303-retifanlimab-anal-cancer-rao-lancet-2025"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04472429","phase":"3","setting":"Untreated inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal: carboplatin and paclitaxel with the PD-1 antibody retifanlimab or placebo (double-blind), with progression-free survival as the primary endpoint","sponsor":"Incyte Corporation","result":"Median progression-free survival 9.3 months with retifanlimab plus carboplatin-paclitaxel against 7.4 months with placebo (hazard ratio 0.63, one-sided p 0.0006); approved in the United States in May 2025.","yearReported":2025,"enrolled":308,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (blinded independent central review)","primary":true,"unit":"months","arms":[{"name":"Retifanlimab + carboplatin + paclitaxel","n":154,"value":9.3,"note":"95% CI 7.5 to 11.3"},{"name":"Placebo + carboplatin + paclitaxel","n":154,"value":7.4,"note":"95% CI 7.1 to 7.7"}],"hr":0.63,"ci":[0.47,0.84],"p":"0.0006 (one-sided)","source":"https://doi.org/10.1016/S0140-6736(25)00631-2"},{"endpoint":"Grade 3 or worse adverse events","unit":"%","arms":[{"name":"Retifanlimab + carboplatin + paclitaxel","n":154,"value":83.1},{"name":"Placebo + carboplatin + paclitaxel","n":154,"value":75}],"source":"https://doi.org/10.1016/S0140-6736(25)00631-2"},{"endpoint":"Serious adverse events","unit":"%","arms":[{"name":"Retifanlimab + carboplatin + paclitaxel","n":154,"value":47.4},{"name":"Placebo + carboplatin + paclitaxel","n":154,"value":38.8}],"source":"https://doi.org/10.1016/S0140-6736(25)00631-2"}]},"route":"/trials/pod1um-303/","neighbours":{"cancer":[{"id":"anal","kind":"cancer","name":"Anal cancer (squamous cell carcinoma)","route":"/cancers/anal/"},{"id":"metastatic-anal-cancer","kind":"cancer","name":"Metastatic and recurrent anal squamous cell carcinoma","route":"/cancers/metastatic-anal-cancer/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"retifanlimab","kind":"drug","name":"Retifanlimab","route":"/drugs/retifanlimab/"}],"company":[{"id":"incyte","kind":"company","name":"Incyte","route":"/companies/incyte/"}],"paper":[{"id":"paper-pod1um-303-retifanlimab-anal-cancer-rao-lancet-2025","kind":"paper","name":"POD1UM-303/InterAACT-2: retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic anal squamous cell carcinoma","route":"/key-papers/paper-pod1um-303-retifanlimab-anal-cancer-rao-lancet-2025/"}]}}