{"entity":{"id":"paper-nct03907852-nat-med-2023","kind":"paper","name":"Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results","aka":[],"tldr":"Published report from the Phase 1 trial registered as NCT03907852, in Nature Medicine (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"The T cell receptor fusion construct (TRuC) gavocabtagene autoleucel (gavo-cel) consists of single-domain anti-mesothelin antibody that integrates into the endogenous T cell receptor (TCR) and engages the signaling capacity of the entire TCR upon mesothelin binding. Here we describe phase 1 results from an ongoing phase1/2 trial of gavo-cel in patients with treatment-refractory mesothelin-expressing solid tumors. The primary objectives were to evaluate safety and determine the recommended phase 2 dose (RP2D). Secondary objectives included efficacy. Thirty-two patients received gavo-cel at increasing doses either as a single agent (n = 3) or after lymphodepletion (LD, n = 29). Dose-limiting toxicities of grade 3 pneumonitis and grade 5 bronchioalveolar hemorrhage were noted. The RP2D was determined as 1 × 10 8 cells per m 2 after LD. Grade 3 or higher pneumonitis was seen in 16% of all patients and in none at the RP2D; grade 3 or higher cytokine release syndrome occurred in 25% of all patients and in 15% at the RP2D. In 30 evaluable patients, the overall response rate and disease control rate were 20% (13% confirmed) and 77%, respectively, and the 6-month overall survival rate was 70%. Gavo-cel warrants further study in patients with mesothelin-expressing cancers given its encouraging anti-tumor activity, but it may have a narrow therapeutic window. ClinicalTrials.gov identifier: NCT03907852.\n\nIndexed on Europe PMC as PubMed record 37501016 (DOI 10.1038/s41591-023-02452-y). Its abstract cites the registry id NCT03907852, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2023","url":"https://doi.org/10.1038/s41591-023-02452-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37501016/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37501016"},{"label":"ClinicalTrials.gov NCT03907852","url":"https://clinicaltrials.gov/study/NCT03907852"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03907852"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2023,"doi":"10.1038/s41591-023-02452-y","pmid":"37501016","authors":"Hassan R, Butler M, O'Cearbhaill RE, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03907852 with the most citations, so it is the natural first reading for anyone following the Phase 1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-nct03907852-nat-med-2023/","neighbours":{"trial":[{"id":"nct03907852","kind":"trial","name":"Phase 1/2 Trial of Gavo-cel (TC-210) in Patients With Advanced Mesothelin-Expressing Cancer","route":"/trials/nct03907852/"}],"journal":[{"id":"nature-medicine","kind":"journal","name":"Nature Medicine","route":"/journals/nature-medicine/"}]}}