dc.contributor.author | Lakhani, N | |
dc.contributor.author | Cosman, R | |
dc.contributor.author | Banerji, U | |
dc.contributor.author | Rasco, D | |
dc.contributor.author | Tomaszewska-Kiecana, M | |
dc.contributor.author | Garralda, E | |
dc.contributor.author | Kornacki, D | |
dc.contributor.author | Li, J | |
dc.contributor.author | Tian, C | |
dc.contributor.author | Bourayou, N | |
dc.contributor.author | Powderly, J | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2024-05-20T11:15:58Z | |
dc.date.available | 2024-05-20T11:15:58Z | |
dc.date.issued | 2024-04-01 | |
dc.identifier | ARTN 102254 | |
dc.identifier | S2059-7029(24)00022-X | |
dc.identifier.citation | ESMO Open, 2024, 9 (4), pp. 102254 - | |
dc.identifier.issn | 2059-7029 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6234 | |
dc.identifier.eissn | 2059-7029 | |
dc.identifier.eissn | 2059-7029 | |
dc.identifier.doi | 10.1016/j.esmoop.2024.102254 | |
dc.identifier.doi | 10.1016/j.esmoop.2024.102254 | |
dc.description.abstract | BACKGROUND: Retifanlimab is a humanized, hinge-stabilized immunoglobulin G4κ monoclonal antibody against human programmed cell death protein 1 (PD-1). This first-in-human, phase I study assessed the safety and efficacy of retifanlimab in patients with advanced solid tumors and identified optimal dosing. PATIENTS AND METHODS: POD1UM-101 was conducted in two parts: (i) dose escalation-evaluated retifanlimab [1 mg/kg every 2 weeks (q2w), 3 or 10 mg/kg q2w or every 4 weeks (q4w)] in patients with relapsed/refractory, unresectable, locally advanced or metastatic solid tumors; (ii) cohort expansion-biomarker-unselected tumor-specific cohorts [endometrial, cervical, sarcoma, non-small-cell lung cancer (NSCLC)] received retifanlimab 3 mg/kg q2w, and tumor-agnostic cohorts received flat dosing [375 mg every 3 weeks (q3w), or 500 and 750 mg q4w]. Primary objectives were safety and tolerability; secondary objective was efficacy in selected tumor types. RESULTS: Thirty-seven patients were enrolled in dose escalation, 134 in PD-1 therapy-naïve tumor-specific cohort expansion (endometrial, n = 29; cervical, NSCLC, soft tissue sarcoma, each n = 35), and 45 in flat dosing (375 mg q3w, 500 and 750 mg q4w, each n = 15). No dose-limiting toxicities occurred during dose escalation; maximum tolerated dose was not reached and 3-mg/kg q2w expansion dose was selected based on safety and pharmacokinetic data. Immune-related adverse events were experienced by 40 patients (30%) in tumor-specific cohorts (most frequently hypothyroidism, hyperthyroidism, colitis, nephritis) and 6 (13%) in flat dosing (most frequently hypothyroidism, hyperthyroidism). Objective response rate (95% confidence interval) was 14% (4.8 to 30.3), 14% (3.9 to 31.7), 20% (8.4 to 36.9), and 3% (0.1 to 14.9) in advanced NSCLC, endometrial, cervical, and sarcoma tumor-specific cohorts that progressed after multiple prior systemic therapies. CONCLUSIONS: Retifanlimab demonstrated clinical pharmacology, safety, and antitumor activity consistent with the programmed death (ligand)-1 inhibitor class. POD1UM-101 results support further exploration of retifanlimab as monotherapy and backbone immunotherapy in combination treatments, with recommended doses of 500 mg q4w and 375 mg q3w. | |
dc.format | Print-Electronic | |
dc.format.extent | 102254 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER | |
dc.relation.ispartof | ESMO Open | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | PD-1 inhibitor | |
dc.subject | checkpoint inhibitor | |
dc.subject | first-in-human | |
dc.subject | retifanlimab | |
dc.subject | solid tumor | |
dc.subject | Humans | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Middle Aged | |
dc.subject | Aged | |
dc.subject | Neoplasms | |
dc.subject | Adult | |
dc.subject | Immune Checkpoint Inhibitors | |
dc.subject | Programmed Cell Death 1 Receptor | |
dc.subject | Antibodies, Monoclonal, Humanized | |
dc.subject | Aged, 80 and over | |
dc.title | A first-in-human phase I study of the PD-1 inhibitor, retifanlimab (INCMGA00012), in patients with advanced solid tumors (POD1UM-101). | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2024-01-14 | |
dc.date.updated | 2024-05-20T11:15:04Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.esmoop.2024.102254 | |
rioxxterms.licenseref.startdate | 2024-04-01 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/38387109 | |
pubs.issue | 4 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Pharmacology – Adaptive Therapy | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1016/j.esmoop.2024.102254 | |
pubs.volume | 9 | |
icr.researchteam | Clinical Pharmacology | |
dc.contributor.icrauthor | Banerji, Udai | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Prof Ros Eeles) on 2024-05-20. Deposit type is initial. No. of files: 1. Files: A first-in-human phase I study of the PD-1 inhibitor, retifanlimab (INCMGA00012), in patients with advanced solid tumors (PO.pdf | |