First-in-human phase I/II, open-label study of mRNA-2416 alone or combined with durvalumab in patients with advanced solid tumors and ovarian cancer
Rattachement africain : us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
BACKGROUND: mRNA-2416 is a novel lipid nanoparticle-encapsulated messenger RNA (mRNA) encoding human OX40 ligand (OX40L) for intratumoral (Itu) injection. OX40L plus immune checkpoint inhibitor (ICI) increased preclinical antitumor activity, thus mRNA-2416 plus ICI may potentiate antitumor activity. METHODS: This first-in-human, phase I/II, open-label, multicenter study examined the safety, tolerability, and efficacy of mRNA-2416 alone (arm A) or with durvalumab (arm B) in patients with advanced solid tumors or lymphoma (NCT03323398). Phase I primary objectives included assessment of safety/tolerability and maximum tolerated dose (MTD)/recommended dose for expansion; phase II arm B dose expansion assessed objective response rate in ovarian cancers. Secondary objectives included pharmacokinetics, disease control rate, duration of response, and progression-free survival (PFS). Assessments of immunologic response to treatment were exploratory. RESULTS: From August 2017 to August 2021, 79 patients were enrolled; 61 received treatment (arm A: 39, arm B: 22), including 16 in the expansion cohort. MTD was not reached. Treatment-related emergent adverse events were primarily grade 1/2, with 8 grade 3 and no grade 4/5 events. On-treatment tumor biopsies demonstrated increased OX40L protein expression, elevated PD-L1, and proinflammatory responses. Tumor shrinkage occurred in injected and surrounding non-injected tumors. Median (95% CI) PFS was 60.0 (50.0 to 108.0) and 50.0 (38.0 to 55.0) days for arms A and B, respectively. CONCLUSIONS: mRNA-2416 alone or with durvalumab was well tolerated. Pharmacodynamic analyses support Itu mRNA proof-of-concept. Predefined primary efficacy endpoints were not met in an exploratory cohort of ovarian cancer. Additional research is warranted to further inform this therapeutic approach.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- First-in-human phase I/II, open-label study of mRNA-2416 alone or combined with durvalumab in patients with advanced solid tumors and ovarian cancer
- Date Crossref
- 01/06/2025
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Massachusetts General Hospital Department of Medicine pays non établi dans la noticeÉtablissement de santé
-
University of Minnesota Department of Obstetrics pays non établi dans la noticeUniversité ou école supérieure
-
Cleveland Clinic Hematology and Medical Oncology pays non établi dans la noticeÉtablissement de santé
-
Northwestern University Department of Obstetrics and Gynecology pays non établi dans la noticeUniversité ou école supérieure
-
Moderna Therapeutics (United States) pays non établi dans la noticeEntreprise
-
University of Colorado Cancer Center Medical Oncology pays non établi dans la noticeÉtablissement de santé
-
University of Colorado Denver pays non établi dans la noticeUniversité ou école supérieure
-
Oncology Research and Clinical Development pays non établi dans la noticeÉtablissement de santé
Department of Medicine — Massachusetts General Hospital, Department of Obstetrics — University of Minnesota et Hematology and Medical Oncology — Cleveland Clinic, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.