{"entity":{"id":"ipatunity130","kind":"trial","name":"IPATunity130","aka":[],"tldr":"IPATunity130 tried to confirm a promising early signal for the AKT-blocking tablet ipatasertib with paclitaxel in triple-negative breast cancers carrying PI3K-pathway mutations. It failed: progression and survival were the same with or without the drug, and the ipatasertib programme in breast cancer ended.","summary":"IPATunity130 (NCT03337724) was a double-blind placebo-controlled phase 3 trial whose cohort A randomised 255 taxane-eligible patients with PIK3CA, AKT1 or PTEN-altered measurable advanced triple-negative breast cancer and no prior chemotherapy for advanced disease 2 to 1 (168 to 87) between February 2018 and April 2020 to ipatasertib 400 mg on days 1 to 21 or placebo, both with paclitaxel 80 mg/m2 on days 1, 8 and 15 every 28 days. The primary endpoint, investigator-assessed progression-free survival, showed no difference (hazard ratio 1.02, 95 percent confidence interval 0.71 to 1.45; medians 7.4 versus 6.1 months), and final overall survival was 24.4 versus 24.9 months (hazard ratio 1.08, 0.73 to 1.58). Ipatasertib added grade 3 or worse diarrhoea (9 versus 2 percent) and dose reductions (39 versus 14 percent) with similar overall grade 3 or worse adverse events (51 versus 46 percent); exploratory PAM50 and Burstein subtype analyses were inconsistent. The randomised phase 2 LOTUS trial had suggested a progression-free survival gain in the biomarker-altered subgroup that this trial did not validate; with CAPItello-290 (capivasertib) it shows that PI3K, AKT or PTEN alteration does not select triple-negative tumours for AKT inhibition. UK sites (registry, 7): Velindre Cardiff, University Hospital Coventry, Beatson Glasgow, Royal Marsden London and Sutton, Derriford Plymouth, Royal Stoke.","status":"negative","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT03337724","url":"https://clinicaltrials.gov/study/NCT03337724"},{"label":"Dent et al., Clinical Cancer Research 2024: ipatasertib plus paclitaxel in PIK3CA/AKT1/PTEN-altered TNBC, IPATunity130 cohort A","url":"https://doi.org/10.1158/1078-0432.CCR-24-0465"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":["pi3k-akt-mtor-inhibitors","cytotoxic-chemotherapy"],"targets":["akt","pik3ca","pten"],"drugs":["ipatasertib","paclitaxel"],"companies":["roche-genentech"],"institutions":[],"pathways":["pi3k-akt-mtor"],"terms":[],"trials":["nct03997123","barbican"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["UK sites (registry, 7): Velindre Cancer Centre Cardiff, University Hospital Coventry, Beatson West of Scotland Cancer Centre Glasgow, Royal Marsden Hospital London and Sutton, Derriford Hospital Plymouth, Royal Stoke University Hospital."],"nct":"NCT03337724","phase":"3","setting":"PIK3CA, AKT1 or PTEN-altered locally advanced unresectable or metastatic triple-negative breast cancer, no prior chemotherapy for advanced disease: first-line paclitaxel with ipatasertib or placebo (cohort A), 30 countries including the United Kingdom","sponsor":"Hoffmann-La Roche","result":"PFS 7.4 vs 6.1 months (HR 1.02, 0.71 to 1.45); OS 24.4 vs 24.9 months (HR 1.08). Negative.","yearReported":2024,"enrolled":255,"enrolledBasis":"randomised","enrolledNote":"ClinicalTrials.gov lists 579 participants across cohorts A (PIK3CA/AKT1/PTEN-altered triple-negative), B (hormone-receptor-positive) and C; the triple-negative cohort A randomised 255 patients.","outcomes":[{"endpoint":"Progression-free survival (investigator), cohort A","primary":true,"unit":"months","arms":[{"name":"Ipatasertib + paclitaxel","n":168,"value":7.4},{"name":"Placebo + paclitaxel","n":87,"value":6.1}],"hr":1.02,"ci":[0.71,1.45],"source":"https://doi.org/10.1158/1078-0432.CCR-24-0465"},{"endpoint":"Overall survival, cohort A","unit":"months","arms":[{"name":"Ipatasertib + paclitaxel","value":24.4},{"name":"Placebo + paclitaxel","value":24.9}],"hr":1.08,"ci":[0.73,1.58],"source":"https://doi.org/10.1158/1078-0432.CCR-24-0465"}],"replication":"Failed to confirm the phase 2 LOTUS signal; CAPItello-290 with capivasertib reached the same negative conclusion for overall survival."},"route":"/trials/ipatunity130/","neighbours":{"cancer":[{"id":"tnbc-metastatic","kind":"cancer","name":"Metastatic triple-negative breast cancer","route":"/cancers/tnbc-metastatic/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"pi3k-akt-mtor-inhibitors","kind":"technology","name":"PI3K, AKT and mTOR inhibitors","route":"/technologies/pi3k-akt-mtor-inhibitors/"}],"target":[{"id":"akt","kind":"target","name":"AKT","route":"/targets/akt/"},{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"},{"id":"pten","kind":"target","name":"PTEN","route":"/targets/pten/"}],"drug":[{"id":"ipatasertib","kind":"drug","name":"Ipatasertib","route":"/drugs/ipatasertib/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"pathway":[{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"}],"trial":[{"id":"barbican","kind":"trial","name":"BARBICAN","route":"/trials/barbican/"},{"id":"nct03997123","kind":"trial","name":"Capivasertib+Paclitaxel as First Line Treatment for Patients With Locally Advanced or Metastatic TNBC","route":"/trials/nct03997123/"},{"id":"lotus","kind":"trial","name":"LOTUS","route":"/trials/lotus/"},{"id":"pakt","kind":"trial","name":"PAKT","route":"/trials/pakt/"}]}}