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

Study Overview
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Brief Summary
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This is a parallel-group, two-staged, Phase 2/3, randomized, multi-center study to investigate the efficacy and safety of REC-2282 in patients with progressive NF2 mutated meningiomas.

Detailed Description
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This is a parallel-group, two-staged, Phase 2/3, randomized, multi-center study to investigate the efficacy and safety of REC-2282 in patients with progressive NF2 mutated meningiomas, with either NF2 disease-related meningioma or recurrent sporadic meningiomas that have NF2 mutations. Cohort A 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). 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.

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

Conditions
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Neurofibromatosis Type 2

Intervention / Treatment
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* Drug: REC-2282
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥12 years of age and weighing at least 40 kg Progressive meningioma that is amenable to volumetric analysis 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) Adequate bone marrow function Has provided written informed consent/assent to participate in the study Exclusion Criteria: Progressive disease associated with significant or disabling clinical symptoms likely to require surgery or radiation therapy within the next 3 months. Received prior surgery, radiosurgery, or laser interstitial thermal therapy in the target tumor, or immediately adjacent to the target tumor within 6 months prior to screening. Received an anti- tumor agent for meningioma within 3 months, or 5 half-lives (whichever is longer), prior to screening. 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. Received another investigational drug within 30 days prior to screening Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during this study or within 90 days after the last dose of IMP.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Parallel-group, Two-staged, Phase 2/3, Randomized, Multicenter Efficacy and Safety Study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A Adults, Dose 40 mg<br> | Drug: REC-2282<br>* Participants will receive REC-2282 3 times per week orally for 3 weeks followed by 1 week off for a 4-week cycle.<br>* Other names: NSC-D736012;|
| Experimental: Cohort A Adults, Dose 60 mg<br> | Drug: REC-2282<br>* Participants will receive REC-2282 3 times per week orally for 3 weeks followed by 1 week off for a 4-week cycle.<br>* Other names: NSC-D736012;|
| Experimental: Cohort A Adolescents<br>Starting dose of 30 mg followed by dose escalation to 40 mg and 60 mg. | Drug: REC-2282<br>* Participants will receive REC-2282 3 times per week orally for 3 weeks followed by 1 week off for a 4-week cycle.<br>* Other names: NSC-D736012;|
| Experimental: Cohort B Active<br>Dose TBD | Drug: REC-2282<br>* Participants will receive REC-2282 3 times per week orally for 3 weeks followed by 1 week off for a 4-week cycle.<br>* Other names: NSC-D736012;|
| Placebo Comparator: Cohort B Placebo<br> | Drug: Placebo<br>* Participants will receive placebo orally 3 times per week for 3 weeks followed by 1 week off for a 4-week cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) in Cohort A | The proportion of participants in Cohort A who are alive and progression-free after 6 cycles of treatment | 6 months | 
| Progression-free survival (PFS) in Cohort B | In Cohort B, the time from the date of randomization until disease progression or death from any cause, whichever occurs first. | Time from the date of randomization until disease progression or death from any cause, whichever occurs first, assessed up to 24 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurofibromatosis Type 2; Neurofibromatosis Type II