{"entity":{"id":"tarlatamab","kind":"drug","name":"Tarlatamab","aka":[],"tldr":"The first T-cell engager to improve survival in a common solid tumour, small-cell lung cancer.","summary":"Accelerated approval May 2024 (DeLLphi-301, ORR 40%); DeLLphi-304 phase 3 (2025) showed OS 13.6 vs 8.3 months versus chemotherapy in second-line SCLC, converting to full approval. First-line combination with PD-L1 (DeLLphi-305) and limited-stage trials ongoing. CRS in ~50% (mostly grade 1-2); step-up dosing with monitoring.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Tarlatamab","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Tarlatamab"},{"label":"NICE TA1091: tarlatamab for extensive-stage small-cell lung cancer after 2 or more treatments (not recommended)","url":"https://www.nice.org.uk/guidance/ta1091"}],"tags":[],"related":[],"cancers":["sclc","extensive-stage-sclc","limited-stage-sclc","lung-cancer"],"sections":[],"technologies":["t-cell-engager"],"targets":["dll3","cd3"],"drugs":[],"companies":["amgen"],"institutions":[],"pathways":[],"terms":["crs"],"trials":["dellphi-304","nct07005128","nct06117774","nct07778316","nct06502977","nct05060016","nct06745323","dellphi-305"],"people":[],"bottlenecks":[],"keyPapers":["paper-dellphi-301-nejm-2023"],"journals":[],"dependsOn":[],"notes":[],"brand":"Imdelltra","modality":"Bispecific T-cell engager (DLL3×CD3)","mechanism":"Half-life-extended BiTE binding DLL3 on tumour and CD3 on T cells.","approvals":[{"region":"US","year":2024,"indication":"Extensive-stage SCLC after platinum chemotherapy"},{"region":"EU","year":2026,"indication":"ES-SCLC after platinum-based chemotherapy; 29 May 2026"},{"region":"England (NICE)","year":2025,"indication":"Extensive-stage small-cell lung cancer progressing after two or more lines of treatment including platinum-based chemotherapy: not recommended","note":"TA1091, published 20 August 2025, says tarlatamab should not be used in the NHS in England for this indication."}],"mechanismSteps":["One arm binds DLL3 on the tumour cell","The other arm binds CD3 on any passing T cell","An artificial immune synapse forms, independent of MHC","The T cell releases perforin and granzymes into the tumour cell","Tumour cell dies; cytokines are released (source of CRS)"],"dosing":{"route":"IV infusion over 1 hour","schedule":"Step-up: 1 mg on cycle 1 day 1, then 10 mg on day 8 and every 2 weeks thereafter","modifications":"Hold for grade 2 CRS/ICANS until resolved; dexamethasone premedication and IV fluids for first two doses","monitoring":"Inpatient monitoring 22-24 h after first two doses; temperature, blood pressure, neurology; ICE score","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e7b6163-5d83-42ea-82c9-cf7620cdc782"},"toxicity":[{"event":"Cytokine release syndrome","anyGradePct":55,"grade3PlusPct":1.6,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e7b6163-5d83-42ea-82c9-cf7620cdc782","note":"DeLLphi-301, n=187"},{"event":"Haemoglobin decreased","anyGradePct":58,"grade3PlusPct":5,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e7b6163-5d83-42ea-82c9-cf7620cdc782","note":"DeLLphi-301, n=187"},{"event":"Fatigue","anyGradePct":51,"grade3PlusPct":10,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e7b6163-5d83-42ea-82c9-cf7620cdc782","note":"DeLLphi-301, n=187"},{"event":"Dysgeusia","anyGradePct":36,"grade3PlusPct":0,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e7b6163-5d83-42ea-82c9-cf7620cdc782","note":"DeLLphi-301, n=187"},{"event":"Pyrexia","anyGradePct":36,"grade3PlusPct":0,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e7b6163-5d83-42ea-82c9-cf7620cdc782","note":"DeLLphi-301, n=187"},{"event":"Decreased appetite","anyGradePct":34,"grade3PlusPct":2.7,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e7b6163-5d83-42ea-82c9-cf7620cdc782","note":"DeLLphi-301, n=187"},{"event":"Musculoskeletal pain","anyGradePct":30,"grade3PlusPct":1.1,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e7b6163-5d83-42ea-82c9-cf7620cdc782","note":"DeLLphi-301, n=187"},{"event":"Constipation","anyGradePct":30,"grade3PlusPct":0.5,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e7b6163-5d83-42ea-82c9-cf7620cdc782","note":"DeLLphi-301, n=187"},{"event":"Nausea","anyGradePct":22,"grade3PlusPct":1.6,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e7b6163-5d83-42ea-82c9-cf7620cdc782","note":"DeLLphi-301, n=187"},{"event":"Neurologic toxicity incl. ICANS","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e7b6163-5d83-42ea-82c9-cf7620cdc782","note":"Boxed warning; ICANS in a minority, mostly grade 1-2"}],"access":[{"country":"US","reimbursement":"Medicare Part B (physician-administered); commercial plans per formulary","assistance":"https://www.amgensupportplus.com","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"},{"country":"UK","reimbursement":"NICE: appraisal for ES-SCLC after platinum in progress (2026)","source":"https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2022-11","type":"designation","region":"US","note":"Breakthrough Therapy designation, ES-SCLC after platinum","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2024-05-16","type":"accelerated-approval","region":"US","note":"Accelerated approval, ES-SCLC after platinum (DeLLphi-301)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"Adult patients with extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy"},{"date":"2025-06","type":"filing","region":"US","note":"Phase 3 DeLLphi-304 OS benefit presented; conversion to full approval pursued","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2025-11-19","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2024 converted to traditional approval 1.5 years after it was granted.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer","indication":"Adult patients with extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy"},{"date":"2025-12","type":"approval","region":"US","note":"Full approval based on DeLLphi-304","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}]},"route":"/drugs/tarlatamab/","neighbours":{"cancer":[{"id":"extensive-stage-sclc","kind":"cancer","name":"Extensive-stage small-cell lung cancer","route":"/cancers/extensive-stage-sclc/"},{"id":"extrapulmonary-nec","kind":"cancer","name":"Extrapulmonary neuroendocrine carcinoma","route":"/cancers/extrapulmonary-nec/"},{"id":"limited-stage-sclc","kind":"cancer","name":"Limited-stage small-cell lung cancer","route":"/cancers/limited-stage-sclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"prostate-nepc","kind":"cancer","name":"Neuroendocrine and small-cell prostate cancer","route":"/cancers/prostate-nepc/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"}],"technology":[{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"}],"target":[{"id":"cd3","kind":"target","name":"CD3","route":"/targets/cd3/"},{"id":"dll3","kind":"target","name":"DLL3","route":"/targets/dll3/"}],"company":[{"id":"amgen","kind":"company","name":"Amgen","route":"/companies/amgen/"}],"term":[{"id":"cancer-stem-cell-theory","kind":"term","name":"Cancer stem cell theory and phenotypic plasticity","route":"/terms/cancer-stem-cell-theory/"},{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"},{"id":"limited-extensive-stage","kind":"term","name":"Limited-stage vs extensive-stage (small-cell lung cancer)","route":"/terms/limited-extensive-stage/"},{"id":"lung-uk-drug-access","kind":"term","name":"Lung cancer drugs in England: what NICE has recommended","route":"/terms/lung-uk-drug-access/"},{"id":"lung-failed-programmes","kind":"term","name":"Lung cancer: the failed and stopped programmes, and why","route":"/terms/lung-failed-programmes/"},{"id":"sclc-molecular-subtypes","kind":"term","name":"Small-cell lung cancer transcription-factor subtypes (SCLC-A, SCLC-N, SCLC-P, SCLC-I) and SLFN11","route":"/terms/sclc-molecular-subtypes/"},{"id":"step-up-dosing","kind":"term","name":"Step-up dosing (T-cell engagers)","route":"/terms/step-up-dosing/"}],"trial":[{"id":"nct05060016","kind":"trial","name":"A Phase 2 Study of Tarlatamab in Patients With Small Cell Lung Cancer (SCLC)","route":"/trials/nct05060016/"},{"id":"nct06745323","kind":"trial","name":"A Phase 2, Open-label, Randomized, Multicenter Study of Tarlatamab Dosing Regimens in Subjects With SCLC","route":"/trials/nct06745323/"},{"id":"nct07005128","kind":"trial","name":"A Study Comparing Tarlatamab, Durvalumab, Carboplatin, and Etoposide Versus Durvalumab, Carboplatin, and Etoposide in First-line Extensive Stage Small","route":"/trials/nct07005128/"},{"id":"nct07203053","kind":"trial","name":"A Trial of Tarlatamab in Patients With Pretreated Extensive-stage Small Cell Lung Cancer (ES-SCLC) and ECOG PS 2","route":"/trials/nct07203053/"},{"id":"dellphi-304","kind":"trial","name":"DeLLphi-304","route":"/trials/dellphi-304/"},{"id":"dellphi-305","kind":"trial","name":"DeLLphi-305","route":"/trials/dellphi-305/"},{"id":"nct07778316","kind":"trial","name":"Phase 3 Trial of Tarlatamab (SC vs IV) in Extensive-Stage Small Cell Lung Cancer After Platinum Based First-line Chemotherapy (ES-SCLC)","route":"/trials/nct07778316/"},{"id":"nct06814496","kind":"trial","name":"Radiation Combined With BIspecific T-Cell Engager in DLL3 Expressing Tumors","route":"/trials/nct06814496/"},{"id":"nct06117774","kind":"trial","name":"Study Evaluating Tarlatamab After Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer (LS-SCLC)","route":"/trials/nct06117774/"},{"id":"nct06502977","kind":"trial","name":"Study Evaluating Tarlatamab in Chinese Participants With Advanced Small Cell Lung Cancer After Two or More Prior Lines of Treatment","route":"/trials/nct06502977/"},{"id":"nct07016230","kind":"trial","name":"Study Investigating Tarlatamab (AMG 757) in Patients With Metastatic/Locally Advanced Small-Cell Lung Cancer (SCLC) and Other Poorly Differentiated Neuroendocri","route":"/trials/nct07016230/"},{"id":"nct07637513","kind":"trial","name":"Tarlatamab and Durvalumab vs. Durvalumab Alone for Limited-Stage-Small Cell Lung Cancer","route":"/trials/nct07637513/"},{"id":"nct07423585","kind":"trial","name":"Tarlatamab for the Treatment of Extensive Stage Small-cell Lung Cancer","route":"/trials/nct07423585/"}],"paper":[{"id":"paper-dellphi-301-nejm-2023","kind":"paper","name":"DeLLphi-301: tarlatamab, a DLL3-targeting T-cell engager, in previously treated small-cell lung cancer","route":"/key-papers/paper-dellphi-301-nejm-2023/"}],"pairing":[{"id":"chemo-io-then-maintenance-sclc","kind":"pairing","name":"Chemo-immunotherapy induction → maintenance intensification (SCLC)","route":"/pairings/chemo-io-then-maintenance-sclc/"},{"id":"tarlatamab-vs-idxd-sequence","kind":"pairing","name":"Sequencing DLL3 engager and B7-H3 ADC in relapsed SCLC","route":"/pairings/tarlatamab-vs-idxd-sequence/"}],"idea":[{"id":"idea-bio1-cfrna-plasticity-tracking","kind":"idea","name":"Detect tumours changing cell type from RNA in the blood","route":"/ideas/idea-bio1-cfrna-plasticity-tracking/"},{"id":"idea-sclc-subtype-directed","kind":"idea","name":"Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)","route":"/ideas/idea-sclc-subtype-directed/"}],"roadmap":[{"id":"immunotherapy-roadmap","kind":"roadmap","name":"Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity","route":"/roadmaps/immunotherapy-roadmap/"}],"drug":[{"id":"obrixtamig","kind":"drug","name":"Obrixtamig","route":"/drugs/obrixtamig/"},{"id":"rovalpituzumab-tesirine","kind":"drug","name":"Rovalpituzumab tesirine","route":"/drugs/rovalpituzumab-tesirine/"}],"person":[{"id":"charles-rudin","kind":"person","name":"Charles M. Rudin","route":"/people/charles-rudin/"},{"id":"lee-se-hoon","kind":"person","name":"Se-Hoon Lee","route":"/people/lee-se-hoon/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"}],"pathway":[{"id":"cancer-stem-cells-plasticity","kind":"pathway","name":"Cancer stem cells & phenotypic plasticity","route":"/pathways/cancer-stem-cells-plasticity/"},{"id":"lineage-plasticity-neuroendocrine","kind":"pathway","name":"Lineage plasticity & neuroendocrine transformation","route":"/pathways/lineage-plasticity-neuroendocrine/"},{"id":"notch","kind":"pathway","name":"Notch signalling","route":"/pathways/notch/"},{"id":"resistance-routes-map","kind":"pathway","name":"Resistance routes: how a blocked pathway comes back","route":"/pathways/resistance-routes-map/"},{"id":"sclc-signalling","kind":"pathway","name":"Small cell lung cancer (KEGG map)","route":"/pathways/sclc-signalling/"}],"institution":[{"id":"12-de-octubre","kind":"institution","name":"Hospital Universitario 12 de Octubre","route":"/institutions/12-de-octubre/"}],"biomarker":[{"id":"dll3-expression","kind":"biomarker","name":"DLL3 expression","route":"/biomarkers/dll3-expression/"}]}}