{"entity":{"id":"inavolisib","kind":"drug","name":"Inavolisib","aka":[],"tldr":"Inavolisib is a PI3K drug that also destroys the mutant protein, approved in 2024 with palbociclib and fulvestrant for PIK3CA-mutant breast cancer.","summary":"Inavolisib is a PI3K-alpha-selective inhibitor that also promotes degradation of the mutant p110-alpha protein, combining enzyme blockade with removal of the target. It is taken as 9 mg once daily with palbociclib and fulvestrant, and was approved in 2024 for PIK3CA-mutant HR-positive, HER2-negative advanced breast cancer on INAVO120, where the triplet improved progression-free survival to 15.0 versus 7.3 months in endocrine-resistant disease, with an overall survival benefit reported in 2025. Roche/Genentech developed it. Hyperglycaemia, stomatitis, neutropenia and rash are the main adverse events. INAVO120 enrolled patients relapsing during or soon after adjuvant endocrine therapy, so its value in other PIK3CA-mutant settings is still being defined. For a newcomer: a PI3K drug that both blocks and destroys the mutant protein.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Inavolisib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Inavolisib"}],"tags":[],"related":["pi3k-pathway-plus-endocrine","pik3ca-hotspot-mutation"],"cancers":["breast-hr-positive","hr-positive-metastatic-post-cdk46"],"sections":[],"technologies":["kinase-inhibitors","pi3k-akt-mtor-inhibitors"],"targets":["pik3ca"],"drugs":[],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["hyperglycaemia"],"trials":["nct07287150","nct05646862","nct07368998","nct07405801","nct05894239","nct06790693","nct07054190"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Itovebi","modality":"Small-molecule PI3Kα inhibitor and degrader","mechanism":"PI3Kα-selective inhibitor that promotes degradation of mutant p110α.","approvals":[{"region":"US","year":2024,"indication":"PIK3CA-mutant HR+/HER2- advanced breast cancer with palbociclib and fulvestrant"},{"region":"EU","year":2025,"indication":"PIK3CA-mutant ER+/HER2- mBC with palbociclib + fulvestrant; 18 Jul 2025"}],"mechanismSteps":["Inavolisib binds mutant and wild-type PI3Kα","It also triggers degradation of the mutant p110α protein","AKT and mTOR signalling downstream collapse","With CDK4/6 and ER blockade, all three growth axes are shut","Endocrine-resistant tumour cells arrest and die"],"dosing":{"route":"Oral","schedule":"9 mg once daily with palbociclib and fulvestrant","modifications":"Reduce to 6 then 3 mg for hyperglycaemia, stomatitis, diarrhoea","monitoring":"Fasting glucose weekly for 4 weeks then every 4 weeks; HbA1c; oral care","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},"toxicity":[{"event":"Neutropenia","note":"INAVO120 triplet: most common grade 3-4 (from palbociclib)"},{"event":"Hyperglycaemia"},{"event":"Stomatitis"},{"event":"Diarrhoea"},{"event":"Rash"},{"event":"Fatigue"}],"access":[{"country":"US","reimbursement":"Medicare Part D (oral); commercial plans per formulary, often with prior authorisation","assistance":"https://www.genentech-access.com","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"},{"country":"UK","reimbursement":"NICE: appraisal for PIK3CA-mutant HR+ breast cancer (2025-26)","source":"https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2024-10-10","type":"approval","region":"US","note":"PIK3CA-mutant HR+/HER2- endocrine-resistant advanced breast cancer with palbociclib and fulvestrant (INAVO120)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2025-06","type":"label-change","region":"US","note":"OS benefit added to label","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}]},"route":"/drugs/inavolisib/","neighbours":{"pairing":[{"id":"pi3k-pathway-plus-endocrine","kind":"pairing","name":"PI3K/AKT-pathway inhibitor + endocrine therapy (± CDK4/6)","route":"/pairings/pi3k-pathway-plus-endocrine/"}],"biomarker":[{"id":"pik3ca-hotspot-mutation","kind":"biomarker","name":"PIK3CA mutation","route":"/biomarkers/pik3ca-hotspot-mutation/"}],"cancer":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"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":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"term":[{"id":"hyperglycaemia","kind":"term","name":"Hyperglycaemia (PI3K/AKT inhibitor class effect)","route":"/terms/hyperglycaemia/"},{"id":"pten-loss","kind":"term","name":"PTEN loss","route":"/terms/pten-loss/"}],"trial":[{"id":"nct07405801","kind":"trial","name":"A Phase II Study Evaluating the Efficacy and Safety of Inavolisib Plus Ribociclib Plus Fulvestrant Versus Placebo Plus Ribociclib Plus Fulvestrant in Participants With Advanced Breast Cancer","route":"/trials/nct07405801/"},{"id":"nct07441512","kind":"trial","name":"A Phase II, Single-arm Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Eribulin in Pretreated Advanced Triple-negative Breast Cancer","route":"/trials/nct07441512/"},{"id":"nct06790693","kind":"trial","name":"A Study Evaluating the Efficacy and Safety of Inavolisib Plus CDK4/6 Inhibitor and Letrozole vs Placebo + CDK4/6i and Letrozole in Participants With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer","route":"/trials/nct06790693/"},{"id":"nct05646862","kind":"trial","name":"A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy","route":"/trials/nct05646862/"},{"id":"nct04802759","kind":"trial","name":"A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer","route":"/trials/nct04802759/"},{"id":"nct05894239","kind":"trial","name":"A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer","route":"/trials/nct05894239/"},{"id":"nct07287150","kind":"trial","name":"A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer","route":"/trials/nct07287150/"},{"id":"nct07054190","kind":"trial","name":"A Study to Test Inavolisib Treatments in Participants With Early-Stage, PIK3CA-Mutated Breast Cancer","route":"/trials/nct07054190/"},{"id":"inavo120","kind":"trial","name":"INAVO120","route":"/trials/inavo120/"},{"id":"nct07368998","kind":"trial","name":"To Study the Effect of Inavolisib in Combination With Fulvestrant in Participants With Breast Cancer","route":"/trials/nct07368998/"},{"id":"nct04589845","kind":"trial","name":"Tumor-agnostic Precision Immuno-oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study","route":"/trials/nct04589845/"}],"idea":[{"id":"idea-ctdna-switch-generalised","kind":"idea","name":"Molecular-progression switching beyond ESR1","route":"/ideas/idea-ctdna-switch-generalised/"}],"pathway":[{"id":"breast-cancer-signalling","kind":"pathway","name":"Breast cancer (KEGG map)","route":"/pathways/breast-cancer-signalling/"},{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"}],"person":[{"id":"komal-jhaveri","kind":"person","name":"Komal Jhaveri","route":"/people/komal-jhaveri/"}],"roadmap":[{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"}]}}