{"entity":{"id":"inavo120","kind":"trial","name":"INAVO120","aka":[],"tldr":"A triple combination that doubled progression-free time and, unusually for this disease, extended survival by seven months in a hard-to-treat group.","summary":"INAVO120, trial NCT04191499 sponsored by Roche and Genentech and reported in 2023, tested a triple combination that doubled progression-free time and, unusually for this disease, extended overall survival in first-line PIK3CA-mutant HR-positive, HER2-negative advanced breast cancer relapsing on or after adjuvant endocrine therapy. It randomised 325 women to inavolisib or placebo with palbociclib and fulvestrant, met its primary progression-free survival endpoint with a large effect, showed a significant survival benefit at the final analysis and a much higher response rate, and led to approval in October 2024; inavolisib degrades mutant p110-alpha, giving less hyperglycaemia than alpelisib. INAVO121 and INAVO122 are ongoing, and whether the benefit extends to later lines is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04191499","url":"https://clinicaltrials.gov/study/NCT04191499"},{"label":"NEJM OS analysis","url":"https://www.nejm.org/doi/abs/10.1056/NEJMoa2501796"}],"tags":[],"related":[],"cancers":["breast-hr-positive","hr-positive-metastatic-post-cdk46"],"sections":[],"technologies":["kinase-inhibitors","pi3k-akt-mtor-inhibitors"],"targets":["pik3ca","cdk4-6"],"drugs":["inavolisib","palbociclib"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["komal-jhaveri"],"bottlenecks":[],"keyPapers":["paper-inavo120-n-engl-j-med-2024","paper-inavo120-n-engl-j-med-2025-update"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04191499","phase":"2/3","setting":"First-line PIK3CA-mutant HR+/HER2- advanced breast cancer relapsing on/after adjuvant endocrine therapy: inavolisib + palbociclib + fulvestrant vs placebo + palbociclib + fulvestrant","sponsor":"Roche / Genentech","result":"PFS 15.0 vs 7.3 months, HR 0.43; OS 34.0 vs 27.0 months, HR 0.67.","started":"2020-01-29","startedType":"actual","yearReported":2023,"enrolled":325,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"Inavolisib + palbociclib + fulvestrant","n":161,"value":15},{"name":"Placebo + palbociclib + fulvestrant","n":164,"value":7.3}],"hr":0.43,"ci":[0.32,0.59],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2404625"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"Inavolisib arm","value":34},{"name":"Placebo arm","value":27}],"hr":0.67,"ci":[0.48,0.94],"p":"0.02","source":"https://www.nejm.org/doi/abs/10.1056/NEJMoa2501796"},{"endpoint":"Objective response rate","unit":"%","arms":[{"name":"Inavolisib arm","value":62.7},{"name":"Placebo arm","value":28}],"source":"https://doi.org/10.1056/NEJMoa2404625"}],"replication":"Single pivotal trial; INAVO121 (vs alpelisib) and INAVO122 (HER2+) ongoing."},"route":"/trials/inavo120/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"hr-positive-metastatic-post-cdk46","kind":"cancer","name":"HR-positive metastatic breast cancer after CDK4/6 inhibitors","route":"/cancers/hr-positive-metastatic-post-cdk46/"}],"technology":[{"id":"pi3k-akt-mtor-inhibitors","kind":"technology","name":"PI3K, AKT and mTOR inhibitors","route":"/technologies/pi3k-akt-mtor-inhibitors/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"cdk4-6","kind":"target","name":"CDK4/6","route":"/targets/cdk4-6/"},{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"}],"drug":[{"id":"fulvestrant","kind":"drug","name":"Fulvestrant","route":"/drugs/fulvestrant/"},{"id":"inavolisib","kind":"drug","name":"Inavolisib","route":"/drugs/inavolisib/"},{"id":"palbociclib","kind":"drug","name":"Palbociclib","route":"/drugs/palbociclib/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"person":[{"id":"komal-jhaveri","kind":"person","name":"Komal Jhaveri","route":"/people/komal-jhaveri/"}],"paper":[{"id":"paper-inavo120-n-engl-j-med-2024","kind":"paper","name":"Inavolisib-Based Therapy in PIK3CA -Mutated Advanced Breast Cancer","route":"/key-papers/paper-inavo120-n-engl-j-med-2024/"},{"id":"paper-inavo120-n-engl-j-med-2025-update","kind":"paper","name":"Overall Survival with Inavolisib in PIK3CA -Mutated Advanced Breast Cancer","route":"/key-papers/paper-inavo120-n-engl-j-med-2025-update/"}]}}