Evidence map›Paper›PMID 40713644›Full record

Trial reportOrphanet journal of rare diseases2025

Safety findings from the phase 1/2 MOSAIC study of miransertib for patients with PIK3CA-related overgrowth spectrum or Proteus syndrome.

Whitney Eng, Ionela Iacobas, Jonathan Perkins, Giuseppe Zampino, Chiara Leoni, Paola Sabrina Buonuomo, Alessandra Simonetti, Himanshu Goel, Michael Briones, Mo Huang 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 Orphanet journal of rare diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03094832 (A Phase 1/2 Study of ARQ 092), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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.

NCT03094832 phase1 / phase2terminatednot on this map

A Phase 1/2 Study of ARQ 092 (Miransertib) in Subjects With PIK3CA-related Overgrowth Spectrum and Proteus Syndrome

TypeinterventionalSponsorArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)Ran2017 to 2022Enrolled50ConditionsPIK3CA-Related Overgrowth Spectrum (PROS)/Proteus SyndromeArmsMiransertib
3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
  2. A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. 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.

Whitney EngBoston Children's Hospital and the Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Whitney.Eng@seattlechildrens.org.ORCID 0000-0002-0103-6000
Ionela IacobasTexas Children's Hospital/Baylor College of Medicine, Houston, TX, USA.
Jonathan PerkinsSeattle Children's Hospital, 4800 Sandpoint Way NE, Seattle, WA, 98115, USA.
Giuseppe ZampinoUniversità Cattolica del Sacro Cuore, Rome, Italy.
Chiara LeoniCenter for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy.
Paola Sabrina BuonuomoOspedale Pediatrico Bambino Gesù, Rome, Italy.
Alessandra SimonettiOspedale Pediatrico Bambino Gesù, Rome, Italy.
Himanshu GoelHunter Genetics, Waratah, NSW, 2298, Australia.
Michael BrionesSchool of Medicine and Aflac Cancer and Blood Disorder Center, Emory University, Atlanta, GA, USA.
Mo HuangMerck & Co., Inc., Rahway, NJ, USA.
Gregory GoldmacherMerck & Co., Inc., Rahway, NJ, USA.
Danny LiawMerck & Co., Inc., Rahway, NJ, USA.
Adrienne HammillCincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Funding

ArQule, IncMerck & Co., Inc., Rahway, NJ, USA
6 · The paper itself

Abstract

backgroundPIK3CA-related overgrowth spectrum (PROS) and Proteus syndrome are associated with mosaic tissue overgrowth of varying severity that commonly presents in childhood. The multicenter, open-label, phase 1/2 MOSAIC study (NCT03094832) was designed to evaluate the clinical efficacy and safety of the selective pan-AKT inhibitor miransertib for participants with PROS or Proteus syndrome.

methodsParticipants ≥ 2 years of age with PROS with documented somatic PIK3CA mutations or Proteus syndrome with documented somatic AKT1 mutations were enrolled to receive oral miransertib at a starting dose of 15 mg/m

resultsBetween May 16, 2017 and January 25, 2021, 49 participants were enrolled and received ≥ 1 dose of study drug, comprising the safety analysis population. Forty-five participants had a diagnosis of PROS and four had a diagnosis of Proteus syndrome. The median (range) age at enrollment was 7 years (2-41). Median (range) duration of treatment was 20.5 months (9.9-45.6). A total of 23 (46.9%) participants had a drug-related adverse event, most commonly decreased neutrophil count (n = 6, 12.2%), increased blood insulin (n = 5, 10.2%), and stomatitis (n = 5, 10.2%). One (2.0%) participant experienced a grade 3 drug-related adverse event (deep vein thrombosis). No drug-related adverse events led to early study discontinuation or death. Laboratory assessment values remained generally stable throughout the study.

conclusionMiransertib was safe and tolerable in participants with a confirmed diagnosis of PROS or Proteus syndrome. Future investigations are needed to determine whether patients receive measurable clinical benefit from miransertib.

trial registrationNCT03094832 registered Mar 28, 2017, https://clinicaltrials.gov/ct2/show/NCT03094832 .

Indexed as

Class I Phosphatidylinositol 3-KinasesProteus SyndromeAdolescentAdultAminopyridinesChildChild, PreschoolFemaleHumansImidazolesMaleMutationYoung AdultAminopyridinesClass I Phosphatidylinositol 3-KinasesImidazolesMiransertibPIK3CA protein, humanAKTMiransertibPIK3CAPIK3CA-related overgrowth spectrumProteus syndrome

Identifiers

PMID40713644
PMCPMC12296598

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.