{"entity":{"id":"capivasertib","kind":"drug","name":"Capivasertib","aka":[],"tldr":"Capivasertib (Truqap) is the first AKT inhibitor, for breast cancer with PI3K-pathway mutations and, since 2026, for prostate cancer with PTEN loss.","summary":"Capivasertib is an ATP-competitive pan-AKT inhibitor given intermittently at 400 mg twice daily for 4 days on and 3 days off, a schedule chosen to limit hyperglycaemia and rash. It was approved in 2023 with fulvestrant for HR-positive, HER2-negative advanced breast cancer carrying PIK3CA, AKT1 or PTEN alterations after CAPItello-291, and in Q2 2026 with abiraterone for PTEN-deficient metastatic hormone-sensitive prostate cancer after CAPItello-281, the first AKT inhibitor in either disease. AstraZeneca markets it. Diarrhoea (77%, 12% grade 3 or higher) and cutaneous reactions (56%, 15%) are the main toxicities. The breast label is limited to tumours with a pathway alteration, and sequencing against PI3K-alpha inhibitors such as inavolisib is unresolved. For a newcomer: a pill that blocks the AKT node of the PI3K pathway in tumours that have switched it on.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Capivasertib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Capivasertib"},{"label":"CAPItello-290 (Annals of Oncology 2026)","url":"https://doi.org/10.1016/j.annonc.2025.12.012"}],"tags":[],"related":["er-status","pik3ca-hotspot-mutation","akt1-e17k","pten-alteration"],"cancers":["breast-hr-positive","prostate","prostate-mhspc","hr-positive-metastatic-post-cdk46","tnbc","tnbc-metastatic"],"sections":[],"technologies":["kinase-inhibitors","pi3k-akt-mtor-inhibitors"],"targets":["akt","pik3ca"],"drugs":[],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":["nct05348577","nct07287917","nct06635447","nct05563220","nct04862663","nct03742102","nct06764186","nct03997123"],"people":[],"bottlenecks":[],"keyPapers":["paper-schmid-pakt-capivasertib-tnbc-jco-2020"],"journals":[],"dependsOn":[],"notes":["Triple-negative breast cancer: CAPItello-290 (812 patients, first-line paclitaxel with or without capivasertib) missed both overall survival endpoints (17.7 versus 18.0 months overall, hazard ratio 0.92; 20.4 months in both arms in PIK3CA, AKT1 or PTEN-altered tumours, hazard ratio 1.05) despite a progression-free survival signal (5.6 versus 5.1 months, hazard ratio 0.72), so the AKT inhibitor has no triple-negative indication and the NICE appraisal for untreated metastatic triple-negative disease (GID-TA11411) was discontinued. With IPATunity130 (ipatasertib) this closes the first-line AKT-inhibitor programme in triple-negative disease that the phase 2 PAKT and LOTUS trials had opened."],"brand":"Truqap","modality":"Small-molecule AKT inhibitor","mechanism":"ATP-competitive pan-AKT inhibitor, intermittent 4-days-on/3-off dosing.","approvals":[{"region":"US","year":2023,"indication":"HR+/HER2- breast cancer with PIK3CA/AKT1/PTEN alteration, with fulvestrant"},{"region":"US","year":2026,"indication":"PTEN-deficient metastatic prostate cancer with abiraterone"},{"region":"EU","year":2024,"indication":"ER+/HER2- mBC with PIK3CA/AKT1/PTEN alteration; 17 Jun 2024"}],"mechanismSteps":["Oral drug is absorbed and reaches the tumour","Binds the ATP pocket (or allosteric site) of AKT1/2/3","Phosphorylation of downstream substrates stops","Intermittent dosing limits hyperglycaemia while PI3K-pathway signalling is suppressed","Oncogene-addicted cells arrest and undergo apoptosis"],"dosing":{"route":"Oral","schedule":"400 mg twice daily for 4 days on, 3 days off, with fulvestrant (breast) or abiraterone plus prednisone (prostate)","modifications":"Reduce to 320 then 240 mg for grade 3 diarrhoea, rash, or hyperglycaemia; hold for fasting glucose >250 mg/dL","monitoring":"Fasting glucose and HbA1c at baseline and periodically; skin; loperamide guidance","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d698c106-2322-401e-b738-cbd83c843ecf"},"toxicity":[{"event":"Diarrhoea","anyGradePct":77,"grade3PlusPct":12,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d698c106-2322-401e-b738-cbd83c843ecf","note":"CAPItello-291"},{"event":"Cutaneous adverse reactions","anyGradePct":56,"grade3PlusPct":15,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d698c106-2322-401e-b738-cbd83c843ecf","note":"CAPItello-291"},{"event":"Fatigue","anyGradePct":38,"grade3PlusPct":1.9,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d698c106-2322-401e-b738-cbd83c843ecf","note":"CAPItello-291"},{"event":"Nausea","anyGradePct":35,"grade3PlusPct":1.3,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d698c106-2322-401e-b738-cbd83c843ecf","note":"CAPItello-291"},{"event":"Stomatitis","anyGradePct":25,"grade3PlusPct":1.9,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d698c106-2322-401e-b738-cbd83c843ecf","note":"CAPItello-291"},{"event":"Vomiting","anyGradePct":21,"grade3PlusPct":1.9,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d698c106-2322-401e-b738-cbd83c843ecf","note":"CAPItello-291"},{"event":"Hyperglycaemia","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d698c106-2322-401e-b738-cbd83c843ecf","note":"Warning: DKA reported"}],"access":[{"country":"US","reimbursement":"Medicare Part D (oral); commercial plans per formulary, often with prior authorisation","assistance":"https://www.astrazeneca-us.com/medicines/access-360","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"},{"country":"UK","reimbursement":"NICE: recommended with fulvestrant for PIK3CA/AKT1/PTEN-altered HR+ breast cancer (TA998)","source":"https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2023-11-16","type":"approval","region":"US","note":"HR+/HER2- breast cancer with PIK3CA/AKT1/PTEN alteration, with fulvestrant (CAPItello-291): first AKT inhibitor","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-06-12","type":"approval","region":"US","note":"PTEN-deficient metastatic prostate cancer with abiraterone (CAPItello-281)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-capivasertib-abiraterone-and-prednisone-pten-deficient-androgen-pathway-modulation"}]},"route":"/drugs/capivasertib/","neighbours":{"biomarker":[{"id":"akt1-e17k","kind":"biomarker","name":"AKT1 E17K mutation","route":"/biomarkers/akt1-e17k/"},{"id":"er-status","kind":"biomarker","name":"ER status (oestrogen receptor by IHC)","route":"/biomarkers/er-status/"},{"id":"pik3ca-hotspot-mutation","kind":"biomarker","name":"PIK3CA mutation","route":"/biomarkers/pik3ca-hotspot-mutation/"},{"id":"pten-alteration","kind":"biomarker","name":"PTEN alteration (sequencing) and PTEN loss (IHC)","route":"/biomarkers/pten-alteration/"}],"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/"},{"id":"prostate-mhspc","kind":"cancer","name":"Metastatic hormone-sensitive prostate cancer","route":"/cancers/prostate-mhspc/"},{"id":"tnbc-metastatic","kind":"cancer","name":"Metastatic triple-negative breast cancer","route":"/cancers/tnbc-metastatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"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":"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/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"trial":[{"id":"nct06764186","kind":"trial","name":"A Phase IIIB Study to Evaluate the Use of Capivasertib in Combination With Fulvestrant in Patients With Advanced Breast Cancer Who Have Relapsed/Progressed on ET and CDK4/6 Inhibitor Reflecting Real World Clinical Practice in Spain","route":"/trials/nct06764186/"},{"id":"nct03742102","kind":"trial","name":"A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer","route":"/trials/nct03742102/"},{"id":"capitello-281","kind":"trial","name":"CAPItello-281","route":"/trials/capitello-281/"},{"id":"capitello-291","kind":"trial","name":"CAPItello-291","route":"/trials/capitello-291/"},{"id":"nct04862663","kind":"trial","name":"Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)","route":"/trials/nct04862663/"},{"id":"nct06635447","kind":"trial","name":"Capivasertib+Fulvestrant asTreatment for Locally Advanced(Inoperable) or Metastatic HR+/HER2- Breast Cancer in Chinese Patients","route":"/trials/nct06635447/"},{"id":"nct03997123","kind":"trial","name":"Capivasertib+Paclitaxel as First Line Treatment for Patients With Locally Advanced or Metastatic TNBC","route":"/trials/nct03997123/"},{"id":"national-lung-matrix-trial","kind":"trial","name":"National Lung Matrix Trial","route":"/trials/national-lung-matrix-trial/"},{"id":"nci-match","kind":"trial","name":"NCI-MATCH (EAY131)","route":"/trials/nci-match/"},{"id":"nct05563220","kind":"trial","name":"Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Participants With Metastatic Breast Cancer","route":"/trials/nct05563220/"},{"id":"pakt","kind":"trial","name":"PAKT","route":"/trials/pakt/"},{"id":"plasmamatch","kind":"trial","name":"plasmaMATCH","route":"/trials/plasmamatch/"},{"id":"nct07287917","kind":"trial","name":"Study of AMXT 1501 and DFMO in Combination With Standard Therapies in Advanced Solid Tumors","route":"/trials/nct07287917/"},{"id":"nct05348577","kind":"trial","name":"Study of Capivasertib + Docetaxel vs Placebo + Docetaxel as Treatment for Metastatic Castration Resistant Prostate Cancer (mCRPC)","route":"/trials/nct05348577/"}],"paper":[{"id":"paper-capitello-291-nejm-2023","kind":"paper","name":"CAPItello-291: capivasertib plus fulvestrant in hormone receptor-positive advanced breast cancer","route":"/key-papers/paper-capitello-291-nejm-2023/"},{"id":"paper-capitello-290-capivasertib-paclitaxel-ann-oncol-2026","kind":"paper","name":"Capivasertib plus paclitaxel as first-line treatment for metastatic triple-negative breast cancer: results from the randomised, global phase III CAPItello-290 trial","route":"/key-papers/paper-capitello-290-capivasertib-paclitaxel-ann-oncol-2026/"},{"id":"paper-schmid-pakt-capivasertib-tnbc-jco-2020","kind":"paper","name":"Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial","route":"/key-papers/paper-schmid-pakt-capivasertib-tnbc-jco-2020/"}],"pairing":[{"id":"pi3k-pathway-plus-endocrine","kind":"pairing","name":"PI3K/AKT-pathway inhibitor + endocrine therapy (± CDK4/6)","route":"/pairings/pi3k-pathway-plus-endocrine/"}],"idea":[{"id":"idea-ctdna-switch-generalised","kind":"idea","name":"Molecular-progression switching beyond ESR1","route":"/ideas/idea-ctdna-switch-generalised/"},{"id":"idea-tr1-start-low-titrate-up-oral-agents","kind":"idea","name":"Start low and step up: individualised titration of oral cancer drugs, randomised","route":"/ideas/idea-tr1-start-low-titrate-up-oral-agents/"}],"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/"},{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}],"institution":[{"id":"icr-london","kind":"institution","name":"The Institute of Cancer Research","route":"/institutions/icr-london/"}],"pathway":[{"id":"ar-signaling","kind":"pathway","name":"Androgen receptor signalling","route":"/pathways/ar-signaling/"},{"id":"breast-cancer-signalling","kind":"pathway","name":"Breast cancer (KEGG map)","route":"/pathways/breast-cancer-signalling/"},{"id":"chemical-carcinogenesis-receptor-activation","kind":"pathway","name":"Chemical carcinogenesis - receptor activation","route":"/pathways/chemical-carcinogenesis-receptor-activation/"},{"id":"choline-metabolism-in-cancer","kind":"pathway","name":"Choline metabolism in cancer","route":"/pathways/choline-metabolism-in-cancer/"},{"id":"micrornas-in-cancer","kind":"pathway","name":"MicroRNAs in cancer","route":"/pathways/micrornas-in-cancer/"},{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"},{"id":"prostate-cancer-signalling","kind":"pathway","name":"Prostate cancer (KEGG map)","route":"/pathways/prostate-cancer-signalling/"},{"id":"blood-brain-barrier-metastasis","kind":"pathway","name":"The blood-brain barrier & brain metastasis","route":"/pathways/blood-brain-barrier-metastasis/"}],"person":[{"id":"nicholas-turner","kind":"person","name":"Nicholas Turner","route":"/people/nicholas-turner/"},{"id":"paul-workman","kind":"person","name":"Paul Workman","route":"/people/paul-workman/"}],"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/"}]}}