Study of Miransertib (MK-7075) in Participants With PIK3CA-related Overgrowth Spectrum and Proteus Syndrome (MOSAIC) (MK-7075-002)

NCT03094832 | Terminated Phase 1 Results FDA Drug

• 5 other identifiers: 7075-002MOSAICARQ 092-103MK-7075-0022016-000558-37
• Study Type: interventional
• Target: 50
• Locations: 4 countries
• Sites: 11

Brief Summary

This is an open label, Phase 1/2 study of oral miransertib (MK-7075) administered to participants at least 2 years of age with phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA)-related Overgrowth Spectrum (PROS) and Proteus Syndrome (PS) (MOSAIC).

Conditions

PIK3CA-Related Overgrowth Spectrum (PROS)/Proteus Syndrome

Keywords

ARQ 092; ArQule; AKT; PIK3CA; Overgrowth; Congenital malformations; Miransertib; MOSAIC

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced an Adverse Event (AE)

  An AE was defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product and does not imply any judgment about causality.

  Up to approximately 48 months

• Number of Participants Who Discontinued Study Treatment Due to an AE

  An AE was defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product and does not imply any judgment about causality.

  Up to approximately 45 months

Study Arms (5)

Part A: Miransertib PROS/PS

EXPERIMENTAL

During Cycles 1-3, participants with either PROS (phosphatidylinositol- 4,5-bisphosphate 3-kinase, catalytic subunit alpha \[PIK3CA\]-related Overgrowth Spectrum) or PS (Proteus syndrome) received miransertib 15 mg/m\^2 once daily (QD) (each cycle length = 28 days). From Cycles 4-48 or until disease progression, unacceptable toxicity, or discontinuation, participants received miransertib dose titrated to 25 mg/m\^2 and then titrated to 35 mg/m\^2 orally QD at the investigator's discretion.

Drug: Miransertib

Part B: Miransertib PROS (Cohort 1)

EXPERIMENTAL

During Cycles 1-3, participants with PROS who have a measurable lesion by volumetric magnetic resonance imaging (MRI) received miransertib 15 mg/m\^2 QD (each cycle length = 28 days). From cycles 4-48 or until disease progression, unacceptable toxicity, or discontinuation, participants received miransertib dose titrated to 25 mg/m\^2 orally QD at the investigator's discretion.

Drug: Miransertib

Part B: Miransertib PS (Cohort 2)

EXPERIMENTAL

During Cycles 1-3, participants with PS who have a measurable lesion by standardized digital photography received miransertib 15 mg/m\^2 QD (each cycle length = 28 days). From cycles 4-48 or until disease progression, unacceptable toxicity, or discontinuation, participants received miransertib dose titrated to 25 mg/m\^2 orally QD at the investigator's discretion.

Drug: Miransertib

Part B: Miransertib PROS/PS (Cohort 3)

EXPERIMENTAL

During Cycles 1-3, participants with PROS or PS who do not meet all the eligibility criteria for Cohorts 1 or 2 received miransertib 15 mg/m\^2 QD (each cycle length = 28 days). From cycles 4-48 or until disease progression, unacceptable toxicity, or discontinuation, participants received miransertib dose titrated to 25 mg/m\^2 orally QD at the investigator's discretion.

Drug: Miransertib

Part B: Miransertib Compassionate Use/Expanded Access (Cohort 4)

EXPERIMENTAL

During cycles 1-48 (each cycle length = 28 days) or until disease progression, unacceptable toxicity, or discontinuation, participants previously treated with miransertib or currently receiving miransertib under Compassionate Use/Expanded Access continued to receive the current dose of miransertib (did not exceed 25 mg/m\^2).

Drug: Miransertib

Interventions

Miransertib DRUG

Miransertib capsules administered orally at an initial dose of 15 mg/m\^2 or 25 mg/m\^2 QD and then titrated up to 25 mg/m\^2 or 35 mg/m\^2 QD at the investigator's discretion.

Also known as: MK-7075, ARQ 092

Part A: Miransertib PROS/PS; Part B: Miransertib Compassionate Use/Expanded Access (Cohort 4); Part B: Miransertib PROS (Cohort 1); Part B: Miransertib PROS/PS (Cohort 3); Part B: Miransertib PS (Cohort 2)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Part A
• Signed informed consent and, when applicable, signed assent
• Male or female participants ≥ 2 years old with body surface area (BSA) of ≥ 0.33 m\^2
• Have a clinical diagnosis of PROS or PS with documented somatic PIK3CA or serine-threonine protein kinase (AKT1) mutations
• Archival or fresh overgrowth tissue sample available to be shipped to Sponsor or designee
• Have poor prognosis, significant morbidity, and/or progressive disease (e.g., worsening of the disease/increase in number or size of the overgrowth lesions in the last 12 months)
• Have measurable disease (at least one overgrowth lesion that can be accurately measured in size by imaging and/or linear or circumference measure)
• Adequate organ function based on screening laboratory values
• If a female is of child-bearing potential, documentation of a negative pregnancy test is required prior to enrollment. Sexually active participants (male and female) must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse while on study and for up to 90 days after ending treatment
• Ability to complete the Quality of Life (QoL) questionnaires by the participant or his/her caregiver
• Part B:
• Signed consent form and when applicable, signed assent
• Archival or fresh overgrowth tissue sample available to be shipped to Sponsor or designee
• Except for Cohort 4, clinically progressive or worsening disease defined as an increase in number or size of the overgrowth lesion(s) in the last 6 months as assessed by the Investigator
• Adequate organ function based on screening laboratory values

You may not qualify if:

• Part A:
• History of Type 1 or 2 uncontrolled diabetes mellitus requiring regular medication (other than metformin or other oral hypoglycemic agents) or fasting glucose ≥ 160 mg/dL (if \> 12 years old) and ≥ 180 mg/dL (if ≤ 12 years old) at the screening visit
• History of significant cardiac disorders:
• Myocardial infarction (MI) or congestive heart failure defined as Class II-IV per the New York Heart Association (NYHA) classification within 6 months of the first dose of miransertib (MI occurring \> 6 months of the first dose of miransertib will be permitted)
• Grade 2 (per NCI CTCAE version 4.03) or worse conduction defect (e.g., right or left bundle branch block); left ventricular ejection fraction (LVEF) \< 50% assessed by echocardiogram/multigated acquisition (MUGA) scan
• Major surgery, radiotherapy, or immunotherapy within four weeks of the first dose of miransertib
• Any experimental systemic therapy for the purpose of treating PROS or PS (e.g., sirolimus, everolimus, high dose steroids) within two weeks of the first dose of miransertib, except for participants who were previously or are currently treated with miransertib under a Compassionate Use/Expanded Access program
• Intolerance of or severe toxicity attributed to v-Akt murine thymoma viral oncogene homolog (AKT) inhibitors (e.g., miransertib, uprosertib, afuresertib, ipatasertib)
• Concurrent severe uncontrolled illness not related to PROS or PS (ongoing or active infection, known human immunodeficiency virus (HIV) infection, malabsorption syndrome, psychiatric illness/substance abuse/social situation that would limit compliance with study requirements)
• Pregnant or breastfeeding
• Inability to comply with study evaluations or to follow drug administration guidelines
• Part B
• History of Type 1 diabetes mellitus or Type 2 uncontrolled diabetes mellitus requiring regular medication (other than metformin or other oral hypoglycemic agents) or fasting glucose ≥ 160 mg/dL (if \> 12 years old) and ≥ 180 mg/dL (if ≤ 12 years old) at the screening visit
• History of significant cardiac disorders:
• Myocardial infarction (MI) or congestive heart failure defined as Class II-IV per the New York Heart Association (NYHA) classification within 6 months of the first dose of miransertib (MI occurring \> 6 months of the first dose of miransertib will be permitted)

Sponsors & Collaborators

• ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA): lead
• Worldwide Clinical Trials: collaborator

Study Sites (11)

Children's Hospital of Atlanta ( Site 0107)

Atlanta, Georgia, 30342, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 0101)

Chicago, Illinois, 60611, United States

Location

Boston Children's Hospital ( Site 0089)

Boston, Massachusetts, 02115, United States

Location

Cincinnati Children's Hospital Medical Center ( Site 0102)

Cincinnati, Ohio, 45229, United States

Location

Texas Children's Hospital ( Site 0104)

Houston, Texas, 77030, United States

Location

Seattle Childrens Hospital ( Site 0103)

Seattle, Washington, 98105, United States

Location

Hunter Genetics ( Site 0201)

Waratah NSW, New South Wales, 2298, Australia

Location

Ospedale Pediatrico Bambino Gesu ( Site 0087)

Rome, Roma, 00165, Italy

Location

Universita di Catania ( Site 0088)

Catania, 95123, Italy

Location

Fondazione Policlinico Universitario A. Gemelli ( Site 0052)

Roma, 00168, Italy

Location

Hospital Sant Joan ( Site 0601)

Esplugues de Llobregat, Barcelona, 08950, Spain

Location

Related Publications (2)

• Eng W, Iacobas I, Perkins J, Zampino G, Leoni C, Buonuomo PS, Simonetti A, Goel H, Briones M, Huang M, Goldmacher G, Liaw D, Hammill A. Safety findings from the phase 1/2 MOSAIC study of miransertib for patients with PIK3CA-related overgrowth spectrum or Proteus syndrome. Orphanet J Rare Dis. 2025 Jul 25;20(1):375. doi: 10.1186/s13023-025-03831-z.

  PMID: 40713644 DERIVED

• Forde K, Resta N, Ranieri C, Rea D, Kubassova O, Hinton M, Andrews KA, Semple R, Irvine AD, Dvorakova V. Clinical experience with the AKT1 inhibitor miransertib in two children with PIK3CA-related overgrowth syndrome. Orphanet J Rare Dis. 2021 Feb 27;16(1):109. doi: 10.1186/s13023-021-01745-0.

  PMID: 33639990 DERIVED

MeSH Terms

Conditions

Hereditary Sensory and Autonomic Neuropathies; Congenital Abnormalities

Interventions

Miransertib

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Limitations and Caveats

Early termination due to business reasons

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 17, 2017
• First Posted: March 29, 2017
• Study Start: May 16, 2017
• Primary Completion: April 11, 2022
• Study Completion: April 11, 2022
• Last Updated: April 13, 2023
• Results First Posted: March 31, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share

Locations

AU (1); US (6); ES (1); IT (3)