Evidence map›Paper›PMID 40515479›Full record

Trial reportThe oncologist2025

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.

Ryan J Sullivan, Oladapo O Yeku, Deanna Teoh, Shilpa Gupta, Daniela Matei, Andressa S Laino, Jing Sun, Lili Zhu, Linh Van, Stephanie Pascarella and 3 more

Registry-linked trialAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The oncologist, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03323398 (A Phase 1/2, Open-Label, Multicenter, Dose Escalation and Efficacy Study of mRNA-2416, a Lipid Nanoparticle Encapsulated mRNA Encoding Human OX40L, for Intratumoral Injection Alone or in Combination With Durvalumab for Patients With Advanced Malignancies), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03323398 phase1 / phase2terminatednot on this map

A Phase 1/2, Open-Label, Multicenter, Dose Escalation and Efficacy Study of mRNA-2416, a Lipid Nanoparticle Encapsulated mRNA Encoding Human OX40L, for Intratumoral Injection Alone or in Combination With Durvalumab for Patients With Advanced Malignancies

TypeinterventionalSponsorModernaTX, Inc.Ran2017 to 2021Enrolled79ConditionsRelapsed/Refractory Solid Tumor Malignancies or Lymphoma, Ovarian CancerArmsmRNA-2416, Durvalumab
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. New approach methodologies (NAMs) for preclinical and translational evaluation of mRNA-lipid nanoparticle (LNP) therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Review
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Ryan J SullivanDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Oladapo O YekuDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Deanna TeohDepartment of Obstetrics, Gynecology and Women's Health, University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA.
Shilpa GuptaHematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.ORCID 0000-0002-8775-503X
Daniela MateiDepartment of Obstetrics and Gynecology, Northwestern University, Chicago, IL, USA.
Andressa S LainoOncology Research and Clinical Development, Oncology, Moderna Therapeutics, Inc., Cambridge, MA, USA.
Jing SunOncology Research and Clinical Development, Oncology, Moderna Therapeutics, Inc., Cambridge, MA, USA.
Lili ZhuOncology Research and Clinical Development, Oncology, Moderna Therapeutics, Inc., Cambridge, MA, USA.
Linh VanOncology Research and Clinical Development, Oncology, Moderna Therapeutics, Inc., Cambridge, MA, USA.
Stephanie PascarellaOncology Research and Clinical Development, Oncology, Moderna Therapeutics, Inc., Cambridge, MA, USA.
Sima J ZacharekOncology Research and Clinical Development, Oncology, Moderna Therapeutics, Inc., Cambridge, MA, USA.
Khanh T DoOncology Research and Clinical Development, Oncology, Moderna Therapeutics, Inc., Cambridge, MA, USA.ORCID 0000-0002-9411-8899
Antonio JimenoMedical Oncology, University of Colorado Cancer Center, Aurora, CO, USA.ORCID 0000-0001-8560-0440

Funding

AstraZenecaModerna, Inc
6 · The paper itself

Abstract

backgroundmRNA-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.

methodsThis 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.

resultsFrom 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.

conclusionsmRNA-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.

Indexed as

Antibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsNeoplasmsOvarian NeoplasmsOX40 LigandRNA, MessengerAdultAgedFemaleHumansMiddle AgedAntibodies, MonoclonaldurvalumabOX40 LigandRNA, Messengeradvanced solid tumorscheckpoint blockadecombination immunotherapymRNA therapyovarian cancerPD-1

Identifiers

PMID40515479
PMCPMC12166121

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.