{"entity":{"id":"paper-dll3-sclc-clin-cancer-res-2019","kind":"paper","name":"Efficacy and Safety of Rovalpituzumab Tesirine in Third-Line and Beyond Patients with DLL3-Expressing, Relapsed/Refractory Small-Cell Lung Cancer: Results From the Phase II TRINITY Study","aka":[],"tldr":"Phase 2 or 3 results paper on DLL3 in Small-cell lung cancer, in Clinical Cancer Research (2019), one of the most cited Europe PMC records with DLL3 in its title.","summary":"Purpose: Although extensive-stage small-cell lung cancer (SCLC) is highly responsive to first-line therapy, virtually all patients develop resistance with short survival. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting delta-like 3 protein (DLL3). This open-label, single-arm, phase II study (TRINITY) assessed safety and efficacy of Rova-T in patients with DLL3-expressing SCLC in the third-line and beyond (3L+) setting.\n\nPatients and methods: Patients with DLL3-expressing SCLC (determined by mouse antibody immunohistochemistry [IHC] assay), and ≥2 prior regimens, received 0.3 mg/kg Rova-T once every 6 weeks for two cycles. During study, a rabbit antibody IHC assay was developed and used for the final analysis, with DLL3-positive and DLL3-high defined as ≥25% and ≥75% of tumor cells positive for DLL3, respectively. The primary endpoints were objective response rate (ORR) and overall survival (OS).\n\nResults: Among 339 patients enrolled, 261 (77%) had two prior lines of therapy and 78 (23%) had ≥3. DLL3-high and DLL3-positive tumors by rabbit IHC were seen in 238 (70%) and 287 (85%) patients, respectively. The remaining 52 (15%) were DLL3-negative only by rabbit IHC or had missing results. ORR was 12.4%, 14.3%, and 13.2% in all, DLL3-high, and DLL3-positive patients, respectively. Median OS was 5.6 months in all patients and 5.7 months in DLL3-high patients. The most common adverse events (AE) were fatigue, photosensitivity reaction, and pleural effusion. Grade 3-5 AEs were seen in 213 (63%) patients.\n\nConclusions: Rova-T is the first targeted agent in SCLC to use DLL3, a novel biomarker. However, results demonstrate modest clinical activity in 3L+ SCLC, with associated toxicities.\n\nIndexed on Europe PMC as PubMed record 31506387 (DOI 10.1158/1078-0432.ccr-19-1133). Its title names DLL3 and its text names Small-cell lung cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article). It was matched automatically to the idea \"Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2019","url":"https://doi.org/10.1158/1078-0432.ccr-19-1133"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31506387/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31506387"}],"tags":["europepmc-ingest"],"related":["lung-cancer-evidence-roadmap","paper-george-sclc-genomic-profiles-nature-2015","paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019"],"cancers":["lung-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2019,"doi":"10.1158/1078-0432.ccr-19-1133","pmid":"31506387","authors":"Morgensztern D, Besse B, Greillier L, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for DLL3 in Small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by DLL3 in the title and Small-cell lung cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},"route":"/key-papers/paper-dll3-sclc-clin-cancer-res-2019/","neighbours":{"roadmap":[{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"}],"paper":[{"id":"paper-george-sclc-genomic-profiles-nature-2015","kind":"paper","name":"Comprehensive genomic profiles of small cell lung cancer","route":"/key-papers/paper-george-sclc-genomic-profiles-nature-2015/"},{"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/"},{"id":"paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019","kind":"paper","name":"Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data","route":"/key-papers/paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019/"}],"cancer":[{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"}],"journal":[{"id":"clinical-cancer-research","kind":"journal","name":"Clinical Cancer Research","route":"/journals/clinical-cancer-research/"}],"idea":[{"id":"idea-sclc-subtype-directed","kind":"idea","name":"Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)","route":"/ideas/idea-sclc-subtype-directed/"}]}}