{"entity":{"id":"rovalpituzumab-tesirine","kind":"drug","name":"Rovalpituzumab tesirine","aka":[],"tldr":"Rovalpituzumab tesirine (Rova-T) was the first drug against DLL3 in small-cell lung cancer. AbbVie bought it for $5.8B and abandoned it after two failed phase 3 trials. The target later worked with a different weapon.","summary":"A DLL3-directed ADC with a PBD dimer payload (DAR ~2). Phase 2 TRINITY showed modest response rates with high toxicity (effusions, oedema, photosensitivity). Phase 3 TAHOE (second line vs topotecan) was stopped for shorter survival in the Rova-T arm; MERU (first-line maintenance) failed. AbbVie ended development in 2019 after the 2016 Stemcentrx acquisition. Tarlatamab, a DLL3×CD3 T-cell engager, later improved survival in the same setting (DeLLphi-304, 2025).\n\nLesson: target validation and modality are separable. DLL3 was the right address; a PBD payload with a narrow window in a frail population was the wrong weapon.","status":"withdrawn","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Rovalpituzumab_tesirine","links":[{"label":"TAHOE phase 3 (J Thorac Oncol 2021)","url":"https://www.jto.org/article/S1556-0864(21)02264-5/fulltext"}],"tags":["failure","lesson:wrong-drug"],"related":[],"cancers":["sclc"],"sections":[],"technologies":["adc"],"targets":["dll3"],"drugs":["tarlatamab"],"companies":["abbvie"],"institutions":[],"pathways":[],"terms":[],"trials":["nct03033511","nct03061812","nct02674568"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"Rova-T, SC16LD6.5","modality":"ADC","payload":"PBD dimer (SC-DR002)","linker":"Cleavable dipeptide","mechanism":"Humanised anti-DLL3 with PBD dimer (SC-DR002) via cleavable linker.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/rovalpituzumab-tesirine/","neighbours":{"cancer":[{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"target":[{"id":"dll3","kind":"target","name":"DLL3","route":"/targets/dll3/"}],"drug":[{"id":"tarlatamab","kind":"drug","name":"Tarlatamab","route":"/drugs/tarlatamab/"}],"company":[{"id":"abbvie","kind":"company","name":"AbbVie (incl. ImmunoGen, Capstan)","route":"/companies/abbvie/"}],"trial":[{"id":"nct03033511","kind":"trial","name":"A Study of Rovalpituzumab Tesirine as Maintenance Therapy Following First- Line Platinum-Based Chemotherapy in Participants With Extensive Stage Small Cell Lung Cancer (MERU)","route":"/trials/nct03033511/"},{"id":"nct03061812","kind":"trial","name":"Study Comparing Rovalpituzumab Tesirine Versus Topotecan in Subjects With Advanced or Metastatic Small Cell Lung Cancer With High Levels of Delta-like Protein 3 (DLL3) and Who Have First Disease Progression During or Following Front-line Platinum-based Chemotherapy (TAHOE)","route":"/trials/nct03061812/"},{"id":"nct02674568","kind":"trial","name":"Study of Rovalpituzumab Tesirine (SC16LD6.5) for Third-Line and Later Treatment of Subjects With Relapsed or Refractory Delta-Like Protein 3-Expressing Small Cell Lung Cancer","route":"/trials/nct02674568/"}],"bottleneck":[{"id":"b-negative-results","kind":"bottleneck","name":"Failures are hidden","route":"/bottlenecks/b-negative-results/"}],"idea":[{"id":"idea-tr2-termination-reports","kind":"idea","name":"Public post-mortem reports when a cancer drug programme is stopped","route":"/ideas/idea-tr2-termination-reports/"}]}}