{"entity":{"id":"carfilzomib","kind":"drug","name":"Carfilzomib","aka":[],"tldr":"Carfilzomib is a second-generation proteasome inhibitor with less nerve damage but more heart and blood-pressure effects.","summary":"Carfilzomib is an epoxyketone that irreversibly binds the beta5 subunit of the proteasome, giving deeper inhibition than bortezomib with much less peripheral neuropathy. In ENDEAVOR, carfilzomib-dexamethasone (Kd) beat bortezomib-dexamethasone (Vd) with PFS 18.7 versus 9.4 months and an OS benefit, underpinning its 2015 approvals after the 2012 accelerated approval in relapsed disease. It is used in KRd and in Isa-Kd and Dara-Kd combinations, mainly in relapsed disease, because ENDURANCE showed no frontline advantage of KRd over VRd in standard-risk patients. The trade-off is cardiovascular: hypertension in 25%, cardiac failure in 5% and dyspnoea in 28% in ENDEAVOR, so blood pressure and cardiac function are monitored. Amgen develops it. It is a stronger proteasome inhibitor that spares the nerves but asks more of the heart.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Carfilzomib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Carfilzomib"}],"tags":[],"related":[],"cancers":["multiple-myeloma","myeloma-relapsed-refractory"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["amgen"],"institutions":[],"pathways":["ubiquitin-proteasome-system"],"terms":[],"trials":["nct05438043","nct05572515","nct06152575","nct06158841","nct05552976","nct03989414","nct06892522","nct05704049","nct07227311","nct02899052","nct04973605","nct02773030"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Kyprolis","modality":"Proteasome inhibitor (irreversible)","mechanism":"Epoxyketone that irreversibly binds the β5 proteasome subunit.","approvals":[{"region":"US","year":2012,"indication":"Relapsed myeloma (accelerated)"},{"region":"US","year":2015,"indication":"With lenalidomide-dexamethasone; with dexamethasone (ENDEAVOR)"}],"mechanismSteps":[],"dosing":{"route":"IV","schedule":"20/56 mg/m2 twice weekly or 20/70 mg/m2 weekly","monitoring":"Blood pressure, cardiac function, renal function, dyspnoea"},"toxicity":[{"event":"Hypertension","anyGradePct":25,"grade3PlusPct":9,"note":"ENDEAVOR"},{"event":"Cardiac failure","grade3PlusPct":5},{"event":"Dyspnoea","anyGradePct":28}],"access":[],"regulatoryEvents":[{"date":"2012-07-20","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","indication":"Multiple myeloma after at least 2 prior therapies including bortezomib and an immunomodulatory agent and disease progression on or within 60 days of completion of the last therapy"},{"date":"2016-01-21","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2012 converted to traditional approval 3.5 years after it was granted.","indication":"Multiple myeloma after at least 2 prior therapies including bortezomib and an immunomodulatory agent and disease progression on or within 60 days of completion of the last therapy"}]},"route":"/drugs/carfilzomib/","neighbours":{"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"plasma-cell-leukaemia","kind":"cancer","name":"Plasma cell leukaemia","route":"/cancers/plasma-cell-leukaemia/"},{"id":"myeloma-relapsed-refractory","kind":"cancer","name":"Relapsed or refractory multiple myeloma","route":"/cancers/myeloma-relapsed-refractory/"},{"id":"waldenstrom","kind":"cancer","name":"Waldenström macroglobulinaemia","route":"/cancers/waldenstrom/"}],"company":[{"id":"amgen","kind":"company","name":"Amgen","route":"/companies/amgen/"}],"pathway":[{"id":"ubiquitin-proteasome-system","kind":"pathway","name":"Ubiquitin-proteasome system & protein homeostasis","route":"/pathways/ubiquitin-proteasome-system/"}],"trial":[{"id":"nct04973605","kind":"trial","name":"A Phase 1b/2 Study of Sonrotoclax (BGB-11417) as Monotherapy and in Various Combinations With Dexamethasone Plus Carfilzomib, Dexamethasone Plus Darat","route":"/trials/nct04973605/"},{"id":"nct07391657","kind":"trial","name":"A Study Comparing AZD0120, a Dual-targeted CAR-T Against B-cell Maturation Antigen (BCMA) and CD19, Versus Standard Regimens in Participants With Rela","route":"/trials/nct07391657/"},{"id":"nct05572515","kind":"trial","name":"A Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants With","route":"/trials/nct05572515/"},{"id":"nct05438043","kind":"trial","name":"A Study of Daratumumab","route":"/trials/nct05438043/"},{"id":"nct06892522","kind":"trial","name":"A Study to Assess Change in Disease Activity and Adverse Events (AE)s in Adult Participants With Multiple Myeloma Receiving T Cell Engaging Bi/Tri-spe","route":"/trials/nct06892522/"},{"id":"nct02773030","kind":"trial","name":"A Study to Determine Dose, Safety, Tolerability and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Subjects With Multiple","route":"/trials/nct02773030/"},{"id":"nct03989414","kind":"trial","name":"A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Tre","route":"/trials/nct03989414/"},{"id":"nct05552976","kind":"trial","name":"A Study to Evaluate Mezigdomide in Combination With Carfilzomib and Dexamethasone (MeziKD) Versus Carfilzomib and Dexamethasone (Kd) in Participants W","route":"/trials/nct05552976/"},{"id":"nct07227311","kind":"trial","name":"A Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin in Combination With Standard of Care in Participants With Relapsed-Refractory Mult","route":"/trials/nct07227311/"},{"id":"nct05704049","kind":"trial","name":"A Study to Investigate Subcutaneous Isatuximab in Combination With Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory","route":"/trials/nct05704049/"},{"id":"nct06152575","kind":"trial","name":"MagnetisMM-32: A Study to Learn About the Study Medicine Called Elranatamab in People With Multiple Myeloma (MM) That Has Come Back After Taking Other","route":"/trials/nct06152575/"},{"id":"nct06158841","kind":"trial","name":"Study Assessing Activity of Intravenous (IV) Etentamig Monotherapy Versus Standard Available Therapies in Adult Participants With Relapsed or Refracto","route":"/trials/nct06158841/"},{"id":"nct02899052","kind":"trial","name":"Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma (MM)","route":"/trials/nct02899052/"}],"target":[{"id":"proteasome","kind":"target","name":"Proteasome (PSMB5)","route":"/targets/proteasome/"}],"person":[{"id":"keith-stewart","kind":"person","name":"A. Keith Stewart","route":"/people/keith-stewart/"},{"id":"aaron-ciechanover","kind":"person","name":"Aaron Ciechanover","route":"/people/aaron-ciechanover/"},{"id":"sundar-jagannath","kind":"person","name":"Sundar Jagannath","route":"/people/sundar-jagannath/"}]}}