Efficacy and Safety of REC-2282 in Patients With Progressive Neurofibromatosis Type 2 (NF2) Mutated Meningiomas (POPLAR-NF2)

A Two-staged, Phase 2/3, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of REC-2282 in Participants With Progressive NF2 Mutated Meningiomas

This is a two-staged, Phase 2/3, randomized, multi-center study to investigate the efficacy and safety of REC-2282 in participants with progressive NF2 mutated meningiomas.

Study Overview

• Status: Terminated
• Conditions: Neurofibromatosis Type 2
• Intervention / Treatment: Drug: REC-2282; Drug: Placebo

Detailed Description

Cohort A (Phase 2) will provide early data on efficacy and safety of REC-2282 in participants with progressive NF2 mutated meningiomas, and provide guidance for the dose in the confirmatory part of the study (Cohort B, Phase 3). The purpose of Cohort B of the study is to assess the efficacy and safety of REC-2282 compared with placebo in participants with progressive NF2 mutated meningiomas.

In both cohorts, there will be a screening period of up to 8 weeks, a treatment period, a 4-week safety follow-up period after the end of treatment, and a 6-month post-study follow-up. The first 8 participants enrolled in Cohort A will complete a food effect run-in sub study. At the end of the study period, participants may be offered participation in an open-label extension (OLE) period.

In Cohort A, adult participants will be randomized to one of two dose levels of REC-2282.

In Cohort B, participants will be randomized to REC-2282 treatment (dose to be determined from Cohort A) arm or placebo arm in a ratio of 2:1.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Los Angeles, California, United States, 90057
      • House Institute
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Hospital
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Sarah Cannon Cancer Institute - HCA Midwest
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota / Masonic Cancer Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ≥12 years of age and weighing at least 40 kg
2. Progressive meningioma that is amenable to volumetric analysis
3. Has either 1) sporadic meningioma with confirmed NF2 mutation; or, 2) confirmed diagnosis of NF2 disease (revised Manchester criteria); or, 3) at least one NF2-related tumor (with pathogenic germline or proven mosaic NF2 variant)
4. Adequate bone marrow function
5. Has provided written informed consent/assent to participate in the study

Exclusion Criteria:

1. Progressive disease associated with significant or disabling clinical symptoms likely to require surgery or radiation therapy within the next 3 months.
2. Received prior surgery, radiosurgery, or laser interstitial thermal therapy in the target tumor, or immediately adjacent to the target tumor within 12 months prior to screening.
3. Received an anti- tumor agent for meningioma within 3 months, or 5 half-lives (whichever is longer), prior to screening.
4. History of an active malignancy within the previous 3 years except for localized cancers that are considered cured, and, in the opinion of the investigator, present a low risk of recurrence.
5. Received another investigational drug within 30 days prior to screening
6. Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during this study or within 90 days after the last dosing cycle.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A Adults, REC-2282 40 mg; Adult participants will receive REC-2282.	Drug: REC-2282; Participants will receive REC-2282 3 times per week orally for 3 weeks followed by 1 week off for a 4-week cycle.; Other Names: OSU-HDAC42; AR-42; NSC-D736012
Experimental: Cohort A Adults, REC-2282 60 mg; Adult participants will receive REC-2282.	Drug: REC-2282; Participants will receive REC-2282 3 times per week orally for 3 weeks followed by 1 week off for a 4-week cycle.; Other Names: OSU-HDAC42; AR-42; NSC-D736012
Experimental: Cohort A Adolescents, REC-2282; Adolescent participants will receive REC-2282.	Drug: REC-2282; Participants will receive REC-2282 3 times per week orally for 3 weeks followed by 1 week off for a 4-week cycle.; Other Names: OSU-HDAC42; AR-42; NSC-D736012
Experimental: Cohort B REC-2282; Participants will receive REC-2282.	Drug: REC-2282; Participants will receive REC-2282 3 times per week orally for 3 weeks followed by 1 week off for a 4-week cycle.; Other Names: OSU-HDAC42; AR-42; NSC-D736012
Placebo Comparator: Cohort B Placebo; Participants will receive placebo.	Drug: Placebo; Participants will receive placebo orally 3 times per week for 3 weeks followed by 1 week off for a 4-week cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort A: Number of Participants with Progression-free survival (PFS) at 6 Months	In Cohort A, PFS is defined as the number of participants who are alive and progression-free at 6 months with progression defined as having an increase of 20% or more in the target tumor identified.	6 months
Cohort B: Number of Participants with PFS up to 3 years	In Cohort B, PFS is defined as the time from the date of randomization until disease progression or death from any cause, whichever occurs first.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort A: Change from Baseline in Target Tumor Volume at 6 Months		6 months
Cohort A: Number of Participants with PFS at 12 and 24 Months	In Cohort A, PFS is defined as the number of participants who are alive and progression-free at 12 and 24 months with progression defined as having an increase of 20% or more in the target tumor identified.	12 and 24 Months
Cohorts A and B: Objective Response Rate (ORR)		Up to 3 years
Cohorts A and B: Disease Control Rate (DCR)		Up to 3 years
Cohorts A and B: Time to Response (TTR)		Up to 3 years
Cohorts A and B: Duration of Response (DOR)		Up to 3 years
Cohorts A and B: Time to Surgery/radiation for Target Tumors		Up to 3 years
Cohorts A and B: Maximum Observed Plasma Concentration (Cmax) of REC-2282		Up to 3 years
Cohorts A and B: Time to Maximum Plasma Concentration (Tmax) of REC-2282		Up to 3 years
Cohorts A and B: Area under the curve from 0 to 24hr (AUC) of REC-2282		Predose to 24 hours postdose

Collaborators and Investigators

• Sponsor: Recursion Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2022
• Primary Completion (Actual): August 18, 2025
• Study Completion (Actual): August 18, 2025

Study Registration Dates

• First Submitted: November 10, 2021
• First Submitted That Met QC Criteria: November 19, 2021
• First Posted (Actual): November 23, 2021

Study Record Updates

• Last Update Posted (Estimated): October 7, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Neurofibromatosis Type 2; Neurofibromatosis Type II
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Genetic Diseases, Inborn; Neoplasms by Histologic Type; Neurodegenerative Diseases; Otorhinolaryngologic Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Heredodegenerative Disorders, Nervous System; Nerve Sheath Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Neuroendocrine Tumors; Ear Diseases; Otorhinolaryngologic Neoplasms; Cranial Nerve Diseases; Neuroma; Cranial Nerve Neoplasms; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Neurofibroma; Neuroma, Acoustic; Neurilemmoma; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurofibromatoses; Neurofibromatosis 2; HDAC-42
• Other Study ID Numbers: REC-2282-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No